279 results on '"Sabra L Klein"'
Search Results
2. Animal models of congenital zika syndrome provide mechanistic insight into viral pathogenesis during pregnancy.
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Harish Narasimhan, Anna Chudnovets, Irina Burd, Andrew Pekosz, and Sabra L Klein
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
In utero Zika virus (ZIKV; family Flaviviridae) infection causes a distinct pattern of birth defects and disabilities in the developing fetus and neonate that has been termed congenital zika syndrome (CZS). Over 8,000 children were affected by the 2016 to 2017 ZIKV outbreak in the Americas, many of whom developed CZS as a result of in utero exposure. To date, there is no consensus about how ZIKV causes CZS; animal models, however, are providing mechanistic insights. Using nonhuman primates, immunocompromised mice, immunocompetent mice, and other animal models (e.g., pigs, sheep, guinea pigs, and hamsters), studies are showing that maternal immunological responses, placental infection and inflammation, as well as viral genetic factors play significant roles in predicting the downstream consequences of in utero ZIKV infection on the development of CZS in offspring. There are thousands of children suffering from adverse consequences of CZS. Therefore, the animal models developed to study ZIKV-induced adverse outcomes in offspring could provide mechanistic insights into how other viruses, including influenza and hepatitis C viruses, impact placental viability and fetal growth to cause long-term adverse outcomes in an effort to identify therapeutic treatments.
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- 2020
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3. Androgen receptor signaling in the lungs mitigates inflammation and improves the outcome of influenza in mice.
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Landon G Vom Steeg, Santosh Dhakal, Yishak A Woldetsadik, Han-Sol Park, Kathleen R Mulka, Emma C Reilly, David J Topham, and Sabra L Klein
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
Circulating androgens can modulate immune cell activity, but the impact of androgens on viral pathogenesis remains unclear. Previous data demonstrate that testosterone reduces the severity of influenza A virus (IAV) infection in male mice by mitigating pulmonary inflammation rather than by affecting viral replication. To examine the immune responses mediated by testosterone to mitigate IAV-induced inflammation, adult male mice remained gonadally intact or were gonadectomized and treated with either placebo or androgen-filled (i.e., testosterone or dihydrotestosterone) capsules prior to sublethal IAV infection. Like intact males, treatment of gonadectomized males with androgens improved the outcome of IAV infection, which was not mediated by changes in the control of virus replication or pulmonary cytokine activity. Instead, androgens accelerated pulmonary leukocyte contraction to limit inflammation. To identify which immune cells were contracting in response to androgens, the composition of pulmonary cellular infiltrates was analyzed and revealed that androgens specifically accelerated the contraction of total pulmonary inflammatory monocytes during peak disease, as well as CD8+ T cells, IAV-specific CD8+ T numbers, cytokine production and degranulation by IAV-specific CD8+ T cells, and the influx of eosinophils into the lungs following clearance of IAV. Neither depletion of eosinophils nor adoptive transfer of CD8+ T cells could reverse the ability of testosterone to protect males against IAV suggesting these were secondary immunologic effects. The effects of testosterone on the contraction of immune cell numbers and activity were blocked by co-administration of the androgen receptor antagonist flutamide and mimicked by treatment with dihydrotestosterone, which was also able to reduce the severity of IAV in female mice. These data suggest that androgen receptor signaling creates a local pulmonary environment that promotes downregulation of detrimental inflammatory immune responses to protect against prolonged influenza disease.
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- 2020
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4. Biological sex impacts COVID-19 outcomes.
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Sabra L Klein, Santosh Dhakal, Rebecca L Ursin, Sharvari Deshpande, Kathryn Sandberg, and Franck Mauvais-Jarvis
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
The current novel coronavirus disease 2019 (COVID-19) pandemic is revealing profound differences between men and women in disease outcomes worldwide. In the United States, there has been inconsistent reporting and analyses of male-female differences in COVID-19 cases, hospitalizations, and deaths. We seek to raise awareness about the male-biased severe outcomes from COVID-19, highlighting the mechanistic differences including in the expression and activity of angiotensin-converting enzyme 2 (ACE2) as well as in antiviral immunity. We also highlight how sex differences in comorbidities, which can be associated with both age and race, impact male-biased outcomes from COVID-19.
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- 2020
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5. Characterizing Emerging Canine H3 Influenza Viruses.
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Luis Martinez-Sobrido, Pilar Blanco-Lobo, Laura Rodriguez, Theresa Fitzgerald, Hanyuan Zhang, Phuong Nguyen, Christopher S Anderson, Jeanne Holden-Wiltse, Sanjukta Bandyopadhyay, Aitor Nogales, Marta L DeDiego, Brian R Wasik, Benjamin L Miller, Carole Henry, Patrick C Wilson, Mark Y Sangster, John J Treanor, David J Topham, Lauren Byrd-Leotis, David A Steinhauer, Richard D Cummings, Jasmina M Luczo, Stephen M Tompkins, Kaori Sakamoto, Cheryl A Jones, John Steel, Anice C Lowen, Shamika Danzy, Hui Tao, Ashley L Fink, Sabra L Klein, Nicholas Wohlgemuth, Katherine J Fenstermacher, Farah El Najjar, Andrew Pekosz, Lauren Sauer, Mitra K Lewis, Kathryn Shaw-Saliba, Richard E Rothman, Zhen-Ying Liu, Kuan-Fu Chen, Colin R Parrish, Ian E H Voorhees, Yoshihiro Kawaoka, Gabriele Neumann, Shiho Chiba, Shufang Fan, Masato Hatta, Huihui Kong, Gongxun Zhong, Guojun Wang, Melissa B Uccellini, Adolfo García-Sastre, Daniel R Perez, Lucas M Ferreri, Sander Herfst, Mathilde Richard, Ron Fouchier, David Burke, David Pattinson, Derek J Smith, Victoria Meliopoulos, Pamela Freiden, Brandi Livingston, Bridgett Sharp, Sean Cherry, Juan Carlos Dib, Guohua Yang, Charles J Russell, Subrata Barman, Richard J Webby, Scott Krauss, Angela Danner, Karlie Woodard, Malik Peiris, R A P M Perera, M C W Chan, Elena A Govorkova, Bindumadhav M Marathe, Philippe N Q Pascua, Gavin Smith, Yao-Tsun Li, Paul G Thomas, and Stacey Schultz-Cherry
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
The continual emergence of novel influenza A strains from non-human hosts requires constant vigilance and the need for ongoing research to identify strains that may pose a human public health risk. Since 1999, canine H3 influenza A viruses (CIVs) have caused many thousands or millions of respiratory infections in dogs in the United States. While no human infections with CIVs have been reported to date, these viruses could pose a zoonotic risk. In these studies, the National Institutes of Allergy and Infectious Diseases (NIAID) Centers of Excellence for Influenza Research and Surveillance (CEIRS) network collaboratively demonstrated that CIVs replicated in some primary human cells and transmitted effectively in mammalian models. While people born after 1970 had little or no pre-existing humoral immunity against CIVs, the viruses were sensitive to existing antivirals and we identified a panel of H3 cross-reactive human monoclonal antibodies (hmAbs) that could have prophylactic and/or therapeutic value. Our data predict these CIVs posed a low risk to humans. Importantly, we showed that the CEIRS network could work together to provide basic research information important for characterizing emerging influenza viruses, although there were valuable lessons learned.
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- 2020
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6. A scoping review of global COVID-19 vaccine hesitancy among pregnant persons
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Imaima Casubhoy, Alyssa Kretz, Heang-Lee Tan, Laura A. St Clair, Maclaine Parish, Hana Golding, Susan J. Bersoff-Matcha, Catherine Pilgrim-Grayson, Leah Berhane, Andrew Pekosz, Heba H. Mostafa, Andrea L. Cox, Irina Burd, Sabra L. Klein, and Rosemary Morgan
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Immunologic diseases. Allergy ,RC581-607 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Uptake of the COVID-19 vaccine among pregnant persons is lower than the general population. This scoping review explored pregnant people’s attitudes towards the COVID-19 vaccine, reasons for vaccine hesitancy, and whether attitudes about COVID-19 vaccines differ by country of origin. A scoping review was conducted across PubMed, Embase, CINHAL, and Scopus. Inclusion criteria were articles published in English from 2019–2022 focused on attitudes towards COVID-19 vaccination among pregnant persons. Data analysis was done via the 5Cs framework for vaccine hesitancy: Constraints, Complacency, Calculation, Confidence, and Collective Responsibility. 44 articles were extracted. A lack of confidence in vaccine safety was the most prevalent theme of hesitancy among pregnant persons. This was largely driven by a lack of access to information about the vaccine as well as mistrust of the vaccine and medical professionals. Meanwhile, vaccine acceptance was mostly driven by a desire to protect themselves and their loved ones. Overall, COVID-19 vaccine hesitancy among pregnant persons continues to be high. Vaccine hesitancy is primarily driven by fear of the unknown side effects of the vaccine on pregnant persons and their fetuses along with a lack of information and medical mistrust. Some differences can be seen between high income and low- and middle-income countries regarding vaccine hesitancy, showing that a single solution cannot be applied to all who are vaccine hesitant. General strategies, however, can be utilized to reduce vaccine hesitancy, including advocating for inclusion of pregnant persons in clinical trials and incorporating consistent COVID-19 vaccine counseling during prenatal appointments.
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- 2024
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7. Sex and gender differences in adverse events following influenza and COVID-19 vaccination
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Anna Yin, Nadia Wang, Patrick J. Shea, Erica N. Rosser, Helen Kuo, Janna R. Shapiro, Katherine Z.J. Fenstermacher, Andrew Pekosz, Richard E. Rothman, Sabra L. Klein, and Rosemary Morgan
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Birth control ,COVID-19 mRNA vaccine ,Seasonal influenza vaccine ,Reactogenicity ,Vaccine hesitancy ,Medicine ,Physiology ,QP1-981 - Abstract
Abstract Introduction Active and passive surveillance studies have found that a greater proportion of females report adverse events (AE) following receipt of either the COVID-19 or seasonal influenza vaccine compared to males. In a predominately young adult female population of healthcare workers, we sought to determine the intersection of biological sex and sociocultural gender differences in prospective active reporting of vaccine outcomes, which remains poorly characterized. Methods This cohort study enrolled Johns Hopkins Health System healthcare workers (HCWs) who were recruited from the mandatory annual fall 2019–2022 influenza vaccine and the fall 2022 COVID-19 bivalent vaccine campaigns. Vaccine recipients were enrolled the day of vaccination and AE surveys were administered two days post-vaccination for bivalent COVID-19 and influenza vaccine recipients. Data were collected regarding the presence of a series of solicited local and systemic AEs. Open-ended answers about participants’ experiences with AEs also were collected for the COVID-19 vaccine recipients. Results Females were more likely to report local AEs after either influenza (OR = 2.28, p = 0.001) or COVID-19 (OR = 2.57, p = 0.008) vaccination compared to males, regardless of age or race. Males and females had comparable probabilities of reporting systemic AEs after either influenza (OR = 1.18, p = 0.552) or COVID-19 (OR = 0.96, p = 0.907) vaccination. Hormonal birth control use did not impact the rates of reported AEs following influenza vaccination among reproductive-aged female HCWs. Women reported more interruptions in their daily routine following COVID-19 vaccination than men and were more likely to seek out self-treatment. More women than men scheduled their COVID-19 vaccination before their days off in anticipation of AEs. Conclusions Our findings highlight the need for sex- and gender-inclusive policies to inform more effective mandatory occupational health vaccination strategies. Further research is needed to evaluate the potential disruption of AEs on occupational responsibilities following mandated vaccination for healthcare workers, a predominately female population, and to more fully characterize the post-vaccination behavioral differences between men and women.
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- 2024
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8. Progesterone-Based Therapy Protects Against Influenza by Promoting Lung Repair and Recovery in Females.
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Olivia J Hall, Nathachit Limjunyawong, Meghan S Vermillion, Dionne P Robinson, Nicholas Wohlgemuth, Andrew Pekosz, Wayne Mitzner, and Sabra L Klein
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
Over 100 million women use progesterone therapies worldwide. Despite having immunomodulatory and repair properties, their effects on the outcome of viral diseases outside of the reproductive tract have not been evaluated. Administration of exogenous progesterone (at concentrations that mimic the luteal phase) to progesterone-depleted adult female mice conferred protection from both lethal and sublethal influenza A virus (IAV) infection. Progesterone treatment altered the inflammatory environment of the lungs, but had no effects on viral load. Progesterone treatment promoted faster recovery by increasing TGF-β, IL-6, IL-22, numbers of regulatory Th17 cells expressing CD39, and cellular proliferation, reducing protein leakage into the airway, improving pulmonary function, and upregulating the epidermal growth factor amphiregulin (AREG) in the lungs. Administration of rAREG to progesterone-depleted females promoted pulmonary repair and improved the outcome of IAV infection. Progesterone-treatment of AREG-deficient females could not restore protection, indicating that progesterone-mediated induction of AREG caused repair in the lungs and accelerated recovery from IAV infection. Repair and production of AREG by damaged respiratory epithelial cell cultures in vitro was increased by progesterone. Our results illustrate that progesterone is a critical host factor mediating production of AREG by epithelial cells and pulmonary tissue repair following infection, which has important implications for women's health.
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- 2016
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9. SeXX Matters in Infectious Disease Pathogenesis.
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Landon G vom Steeg and Sabra L Klein
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Published
- 2016
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10. Elevated 17β-estradiol protects females from influenza A virus pathogenesis by suppressing inflammatory responses.
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Dionne P Robinson, Maria E Lorenzo, William Jian, and Sabra L Klein
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
Studies of the 1918 H1N1 influenza pandemic, the H5N1 avian influenza outbreak, and the 2009 H1N1 pandemic illustrate that sex and pregnancy contribute to severe outcome from infection, suggesting a role for sex steroids. To test the hypothesis that the sexes respond differently to influenza, the pathogenesis of influenza A virus infection was investigated in adult male and female C57BL/6 mice. Influenza infection reduced reproductive function in females and resulted in greater body mass loss, hypothermia, and mortality in females than males. Whereas lung virus titers were similar between the sexes, females had higher induction of proinflammatory cytokines and chemokines, including TNF-α, IFN-γ, IL-6, and CCL2, in their lungs than males. Removal of the gonads in both sexes eliminated the sex difference in influenza pathogenesis. Manipulation of testosterone or dihydrotestosterone concentrations in males did not significantly impact virus pathogenesis. Conversely, females administered high doses of estradiol had a ≥10-fold lower induction of TNF-α and CCL2 in the lungs and increased rates of survival as compared with females that had either low or no estradiol. The protective effects of estradiol on proinflammatory cytokines and chemokines, morbidity, and mortality were primarily mediated by signaling through estrogen receptor α (ERα). In summary, females suffer a worse outcome from influenza A virus infection than males, which can be reversed by administration of high doses of estradiol to females and reflects differences in the induction of proinflammatory responses and not in virus load.
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- 2011
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11. Trophic garnishes: cat-rat interactions in an urban environment.
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Gregory E Glass, Lynne C Gardner-Santana, Robert D Holt, Jessica Chen, Timothy M Shields, Manojit Roy, Stephen Schachterle, and Sabra L Klein
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Medicine ,Science - Abstract
BACKGROUND:Community interactions can produce complex dynamics with counterintuitive responses. Synanthropic community members are of increasing practical interest for their effects on biodiversity and public health. Most studies incorporating introduced species have been performed on islands where they may pose a risk to the native fauna. Few have examined their interactions in urban environments where they represent the majority of species. We characterized house cat (Felis catus) predation on wild Norway rats (Rattus norvegicus), and its population effects in an urban area as a model system. Three aspects of predation likely to influence population dynamics were examined; the stratum of the prey population killed by predators, the intensity of the predation, and the size of the predator population. METHODOLOGY/PRINCIPAL FINDINGS:Predation pressure was estimated from the sizes of the rat and cat populations, and the characteristics of rats killed in 20 alleys. Short and long term responses of rat population to perturbations were examined by removal trapping. Perturbations removed an average of 56% of the rats/alley but had no negative long-term impact on the size of the rat population (49.6+/-12.5 rats/alley and 123.8+/-42.2 rats/alley over two years). The sizes of the cat population during two years (3.5 animals/alley and 2.7 animals/alley) also were unaffected by rat population perturbations. Predation by cats occurred in 9/20 alleys. Predated rats were predominantly juveniles and significantly smaller (144.6 g+/-17.8 g) than the trapped rats (385.0 g+/-135.6 g). Cats rarely preyed on the larger, older portion of the rat population. CONCLUSIONS/SIGNIFICANCE:The rat population appears resilient to perturbation from even substantial population reduction using targeted removal. In this area there is a relatively low population density of cats and they only occasionally prey on the rat population. This occasional predation primarily removes the juvenile proportion of the rat population. The top predator in this urban ecosystem appears to have little impact on the size of the prey population, and similarly, reduction in rat populations doesn't impact the size of the cat population. However, the selected targeting of small rats may locally influence the size structure of the population which may have consequences for patterns of pathogen transmission.
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- 2009
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12. Immunological mechanisms mediating hantavirus persistence in rodent reservoirs.
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Judith D Easterbrook and Sabra L Klein
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
Hantaviruses, similar to several emerging zoonotic viruses, persistently infect their natural reservoir hosts, without causing overt signs of disease. Spillover to incidental human hosts results in morbidity and mortality mediated by excessive proinflammatory and cellular immune responses. The mechanisms mediating the persistence of hantaviruses and the absence of clinical symptoms in rodent reservoirs are only starting to be uncovered. Recent studies indicate that during hantavirus infection, proinflammatory and antiviral responses are reduced and regulatory responses are elevated at sites of increased virus replication in rodents. The recent discovery of structural and non-structural proteins that suppress type I interferon responses in humans suggests that immune responses in rodent hosts could be mediated directly by the virus. Alternatively, several host factors, including sex steroids, glucocorticoids, and genetic factors, are reported to alter host susceptibility and may contribute to persistence of hantaviruses in rodents. Humans and reservoir hosts differ in infection outcomes and in immune responses to hantavirus infection; thus, understanding the mechanisms mediating viral persistence and the absence of disease in rodents may provide insight into the prevention and treatment of disease in humans. Consideration of the coevolutionary mechanisms mediating hantaviral persistence and rodent host survival is providing insight into the mechanisms by which zoonotic viruses have remained in the environment for millions of years and continue to be transmitted to humans.
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- 2008
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13. Estradiol mediates greater germinal center responses to influenza vaccination in female than male mice
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Santosh Dhakal, Han-Sol Park, Kumba Seddu, John S. Lee, Patrick S. Creisher, Brittany Seibert, Kimberly M. Davis, Isabella R. Hernandez, Robert W. Maul, and Sabra L. Klein
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influenza vaccines ,sex steroids ,B-cell responses ,plasmablast ,neutralizing antibodies ,somatic hypermutation ,Microbiology ,QR1-502 - Abstract
ABSTRACTAdult females of reproductive age develop greater antibody responses to inactivated influenza vaccines (IIV) than males. How sex, age, and sex steroid concentrations impact B cells and durability of IIV-induced immunity and protection over 4 months post-vaccination (mpv) was analyzed. Vaccinated adult females had greater germinal center B cell and plasmablast frequencies in lymphoid tissues, higher neutralizing antibody responses 1–4 mpv, and better protection against live H1N1 challenge than adult males. Aged mice, regardless of sex, had reduced B cell frequencies, less durable antibody responses, and inferior protection after challenge than adult mice, which correlated with diminished estradiol among aged females. To confirm that greater IIV-induced immunity was caused by sex hormones, four core genotype (FCG) mice were used, in which the testes-determining gene, Sry, was deleted from chromosome Y (ChrY) and transferred to Chr3 to separate gonadal sex (i.e., ovaries or testes) from sex chromosome complement (i.e., XX or XY complement). Vaccinated, gonadal female FCG mice (XXF and XYF) had greater numbers of B cells, higher antiviral antibody titers, and reduced pulmonary virus titers following live H1N1 challenge than gonadal FCG males (XYM and XXM). To establish that lower estradiol concentrations cause diminished immunity, adult and aged females received either a placebo or estradiol replacement therapy prior to IIV. Estradiol replacement significantly increased IIV-induced antibody responses and reduced morbidity after the H1N1 challenge among aged females. These data highlight that estradiol is a targetable mechanism mediating greater humoral immunity following vaccination among adult females.IMPORTANCEFemales of reproductive ages develop greater antibody responses to influenza vaccines than males. We hypothesized that female-biased immunity and protection against influenza were mediated by estradiol signaling in B cells. Using diverse mouse models ranging from advanced-age mice to transgenic mice that separate sex steroids from sex chromosome complement, those mice with greater concentrations of estradiol consistently had greater numbers of antibody-producing B cells in lymphoid tissue, higher antiviral antibody titers, and greater protection against live influenza virus challenge. Treatment of aged female mice with estradiol enhanced vaccine-induced immunity and protection against disease, suggesting that estradiol signaling in B cells is critical for improved vaccine outcomes in females.
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- 2024
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14. Erratum for Karaba et al., 'Endemic Human Coronavirus Antibody Levels Are Unchanged after Convalescent or Control Plasma Transfusion for Early Outpatient COVID-19 Treatment'
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Andrew H. Karaba, Trevor S. Johnston, Evan Beck, Oliver Laeyendecker, Andrea L. Cox, Sabra L. Klein, and David J. Sullivan
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Microbiology ,QR1-502 - Published
- 2024
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15. Reduced control of SARS-CoV-2 infection associates with lower mucosal antibody responses in pregnancy
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Laura A. St Clair, Raghda E. Eldesouki, Jaiprasath Sachithanandham, Anna Yin, Amary Fall, C. Paul Morris, Julie M. Norton, Omar Abdullah, Santosh Dhakal, Caelan Barranta, Hana Golding, Susan J. Bersoff-Matcha, Catherine Pilgrim-Grayson, Leah Berhane, Andrea L. Cox, Irina Burd, Andrew Pekosz, Heba H. Mostafa, Eili Y. Klein, and Sabra L. Klein
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COVID-19 ,gestation ,breakthrough infection ,Omicron variant ,Delta variant ,Microbiology ,QR1-502 - Abstract
ABSTRACTPregnant patients are at greater risk of hospitalization with severe COVID-19 than non-pregnant people. This was a retrospective observational cohort study of remnant clinical specimens from patients who visited acute care hospitals within the Johns Hopkins Health System in the Baltimore, MD–Washington DC, area between October 2020 and May 2022. Participants included confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pregnant people and matched non-pregnant people (the matching criteria included age, race/ethnicity, area deprivation index, insurance status, and vaccination status to ensure matched demographics). The primary dependent measures were clinical COVID-19 outcomes, infectious virus recovery, viral RNA levels, and mucosal anti-spike (S) IgG titers from upper respiratory tract samples. A total of 452 individuals (117 pregnant and 335 non-pregnant) were included in the study, with both vaccinated and unvaccinated individuals represented. Pregnant patients were at increased risk of hospitalization (odds ratio [OR] = 4.2; confidence interval [CI] = 2.0–8.6), intensive care unit admittance (OR = 4.5; CI = 1.2–14.2), and being placed on supplemental oxygen therapy (OR = 3.1; CI = 1.3–6.9). Individuals infected during their third trimester had higher mucosal anti-S IgG titers and lower viral RNA levels (P < 0.05) than those infected during their first or second trimesters. Pregnant individuals experiencing breakthrough infections due to the Omicron variant had reduced anti-S IgG compared to non-pregnant patients (P < 0.05). The observed increased severity of COVID-19 and reduced mucosal antibody responses particularly among pregnant participants infected with the Omicron variant suggest that maintaining high levels of SARS-CoV-2 immunity through booster vaccines may be important for the protection of this at-risk population.IMPORTANCEIn this retrospective observational cohort study, we analyzed remnant clinical samples from non-pregnant and pregnant individuals with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections who visited the Johns Hopkins Hospital System between October 2020 and May 2022. Disease severity, including intensive care unit admission, was greater among pregnant than non-pregnant patients. Vaccination reduced recovery of infectious virus and viral RNA levels in non-pregnant patients, but not in pregnant patients. In pregnant patients, increased nasopharyngeal viral RNA levels and recovery of infectious virus were associated with reduced mucosal IgG antibody responses, especially among women in their first trimester of pregnancy or experiencing breakthrough infections from Omicron variants. Taken together, this study provides insights into how pregnant patients are at greater risk of severe COVID-19. The novelty of this study is that it focuses on the relationship between the mucosal antibody response and its association with virus load and disease outcomes in pregnant people, whereas previous studies have focused on serological immunity. Vaccination status, gestational age, and SARS-CoV-2 omicron variant impact mucosal antibody responses and recovery of infectious virus from pregnant patients.
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- 2024
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16. Suppression of progesterone by influenza A virus mediates adverse maternal and fetal outcomes in mice
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Patrick S. Creisher, Maclaine A. Parish, Jun Lei, Jin Liu, Jamie L. Perry, Ariana D. Campbell, Morgan L. Sherer, Irina Burd, and Sabra L. Klein
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cytokine storm ,macrophages ,placenta ,pregnancy ,prostaglandins ,progestins ,Microbiology ,QR1-502 - Abstract
ABSTRACT Influenza A virus infection during pregnancy can cause adverse maternal and fetal outcomes but the mechanism responsible remains elusive. Infection of outbred mice with 2009 H1N1 at embryonic day (E) 10 resulted in significant maternal morbidity, placental tissue damage and inflammation, fetal growth restriction, and developmental delays that lasted through weaning. Restriction of pulmonary virus replication was not inhibited during pregnancy, but infected dams had suppressed circulating and placental progesterone (P4) concentrations that were caused by H1N1-induced upregulation of pulmonary cyclooxygenase (COX)-1-, but not COX-2-, dependent synthesis and secretion of prostaglandin (PG) F2α. Treatment with 17-α-hydroxyprogesterone caproate (17-OHPC), a synthetic progestin that is safe to use in pregnancy, ameliorated the adverse maternal and fetal outcomes from H1N1 infection and prevented placental cell death and inflammation. These findings highlight the therapeutic potential of progestin treatments for influenza during pregnancy.IMPORTANCEPregnant individuals are at risk of severe outcomes from both seasonal and pandemic influenza A viruses. Influenza infection during pregnancy is associated with adverse fetal outcomes at birth and adverse consequences for offspring into adulthood. When outbred dams, with semi-allogenic fetuses, were infected with 2009 H1N1, in addition to pulmonary virus replication, lung damage, and inflammation, the placenta showed evidence of transient cell death and inflammation that was mediated by increased activity along the arachidonic acid pathway leading to suppression of circulating progesterone. Placental damage and suppressed progesterone were associated with detrimental effects on perinatal growth and developmental delays in offspring. Treatment of H1N1-infected pregnant mice with 17-OHPC, a synthetic progestin treatment that is safe to use in pregnancy, prevented placental damage and inflammation and adverse fetal outcomes. This novel therapeutic option for the treatment of influenza during pregnancy should be explored clinically.
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- 2024
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17. Erratum for Gebo et al., 'Early antibody treatment, inflammation, and risk of post-COVID conditions'
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Kelly A. Gebo, Sonya L. Heath, Yuriko Fukuta, Xianming Zhu, Sheriza Baksh, Allison G. Abraham, Feben Habtehyimer, David Shade, Jessica Ruff, Malathi Ram, Oliver Laeyendecker, Reinaldo E. Fernandez, Eshan U. Patel, Owen R. Baker, Shmuel Shoham, Edward R. Cachay, Judith S. Currier, Jonathan M. Gerber, Barry Meisenberg, Donald N. Forthal, Laura L. Hammitt, Moises A. Huaman, Adam Levine, Giselle S. Mosnaim, Bela Patel, James H. Paxton, Jay S. Raval, Catherine G. Sutcliffe, Shweta Anjan, Thomas Gniadek, Seble Kassaye, Janis E. Blair, Karen Lane, Nichol A. McBee, Amy L. Gawad, Piyali Das, Sabra L. Klein, Andrew Pekosz, Evan M. Bloch, Daniel Hanley, Arturo Casadevall, Aaron A. R. Tobian, and David J. Sullivan
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Microbiology ,QR1-502 - Published
- 2024
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18. COVID-19 convalescent plasma therapy decreases inflammatory cytokines: a randomized controlled trial
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Feben Habtehyimer, Xianming Zhu, Andrew D. Redd, Kelly A. Gebo, Alison G. Abraham, Eshan U. Patel, Oliver Laeyendecker, Thomas J. Gniadek, Reinaldo E. Fernandez, Owen R. Baker, Malathi Ram, Edward R. Cachay, Judith S. Currier, Yuriko Fukuta, Jonathan M. Gerber, Sonya L. Heath, Barry Meisenberg, Moises A. Huaman, Adam C. Levine, Aarthi Shenoy, Shweta Anjan, Janis E. Blair, Daniel Cruser, Donald N. Forthal, Laura L. Hammitt, Seble Kassaye, Giselle S. Mosnaim, Bela Patel, James H. Paxton, Jay S. Raval, Catherine G. Sutcliffe, Matthew Abinante, Kevin S. Oei, Valerie Cluzet, Marie Elena Cordisco, Benjamin Greenblatt, William Rausch, David Shade, Amy L. Gawad, Sabra L. Klein, Andrew Pekosz, Shmuel Shoham, Arturo Casadevall, Evan M. Bloch, Daniel Hanley, Aaron A. R. Tobian, and David J. Sullivan
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COVID-19 ,COVID-19 serotherapy ,convalescent plasma ,SARS-CoV-2 ,cytokines ,chemokines ,Microbiology ,QR1-502 - Abstract
ABSTRACT Early COVID-19 convalescent plasma (CCP) transfusion to outpatients with COVID-19 decreases progression to hospitalization, but the mechanism of how CCP reduces severity is unknown. Among 882 COVID-19 participants transfused with CCP or control plasma in a randomized controlled trial, 21 cytokines and chemokines were measured using electrochemiluminescence assays. Wilcoxon rank sum tests were used to evaluate the difference between early (transfused within 5 days of symptom onset) CCP vs early control plasma and late (transfused 6–9 days after symptom onset) CCP vs late control plasma at each visit. Linear mixed-effect models were used to assess the difference in the slope of cytokine change. Median cytokine and chemokine levels were similar between the early CCP and early control groups pre-transfusion. At the day 14 visit, only the median IL-6 (P = 0.014) and IL-16 (P = 0.036) levels were lower in the early CCP group compared to the early control group, but these differences were not statistically significant after correcting for multiple comparisons (requiring P < 0.0024). IL-6 levels decreased significantly faster in the early CCP group from screening to the day 14 visit compared to the early control group (P < 0.001). No difference was observed in the slope of cytokine change from screening to day 90 between early CCP and early control groups. Late control and late CCP arms showed similar cytokine and chemokine levels through study follow-up. One mechanism by which early CCP transfusion reduces hospitalization may be by decreasing IL-6 levels, as the reduction is associated with better recovery from COVID-19. IMPORTANCE This study examined the role that cytokines may have played in the beneficial outcomes found when outpatient individuals infected with SARS-CoV-2 were transfused with COVID-19 convalescent plasma (CCP) early in their infection. We found that the pro-inflammatory cytokine IL-6 decreased significantly faster in patients treated early with CCP. Participants with COVID-19 treated with CCP later in the infection did not have the same effect. This decrease in IL-6 levels after early CCP treatment suggests a possible role of inflammation in COVID-19 progression. The evidence of IL-6 involvement brings insight into the possible mechanisms involved in CCP treatment mitigating SARS-CoV-2 severity.
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- 2024
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19. The Serological Sciences Network (SeroNet) for COVID-19: Depth and Breadth of Serology Assays and Plans for Assay Harmonization
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Amy B. Karger, James D. Brien, Jayne M. Christen, Santosh Dhakal, Troy J. Kemp, Sabra L. Klein, Ligia A. Pinto, Lakshmanane Premkumar, John D. Roback, Raquel A. Binder, Karl W. Boehme, Suresh Boppana, Carlos Cordon-Cardo, James M. Crawford, John L. Daiss, Alan P. Dupuis, Ana M. Espino, Adolfo Firpo-Betancourt, Catherine Forconi, J. Craig Forrest, Roxie C. Girardin, Douglas A. Granger, Steve W. Granger, Natalie S. Haddad, Christopher D. Heaney, Danielle T. Hunt, Joshua L. Kennedy, Christopher L. King, Florian Krammer, Kate Kruczynski, Joshua LaBaer, F. Eun-Hyung Lee, William T. Lee, Shan-Lu Liu, Gerard Lozanski, Todd Lucas, Damodara Rao Mendu, Ann M. Moormann, Vel Murugan, Nkemakonam C. Okoye, Petraleigh Pantoja, Anne F. Payne, Jin Park, Swetha Pinninti, Amelia K. Pinto, Nora Pisanic, Ji Qiu, Carlos A. Sariol, Viviana Simon, Lusheng Song, Tara L. Steffen, E. Taylor Stone, Linda M. Styer, Mehul S. Suthar, Stefani N. Thomas, Bharat Thyagarajan, Ania Wajnberg, Jennifer L. Yates, and Kimia Sobhani
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COVID-19 ,SeroNet ,assay harmonization ,serology ,Microbiology ,QR1-502 - Abstract
ABSTRACT In October 2020, the National Cancer Institute (NCI) Serological Sciences Network (SeroNet) was established to study the immune response to COVID-19, and “to develop, validate, improve, and implement serological testing and associated technologies” (https://www.cancer.gov/research/key-initiatives/covid-19/coronavirus-research-initiatives/serological-sciences-network). SeroNet is comprised of 25 participating research institutions partnering with the Frederick National Laboratory for Cancer Research (FNLCR) and the SeroNet Coordinating Center. Since its inception, SeroNet has supported collaborative development and sharing of COVID-19 serological assay procedures and has set forth plans for assay harmonization. To facilitate collaboration and procedure sharing, a detailed survey was sent to collate comprehensive assay details and performance metrics on COVID-19 serological assays within SeroNet. In addition, FNLCR established a protocol to calibrate SeroNet serological assays to reference standards, such as the U.S. severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology standard reference material and first WHO international standard (IS) for anti-SARS-CoV-2 immunoglobulin (20/136), to facilitate harmonization of assay reporting units and cross-comparison of study data. SeroNet institutions reported development of a total of 27 enzyme-linked immunosorbent assay (ELISA) methods, 13 multiplex assays, and 9 neutralization assays and use of 12 different commercial serological methods. FNLCR developed a standardized protocol for SeroNet institutions to calibrate these diverse serological assays to reference standards. In conclusion, SeroNet institutions have established a diverse array of COVID-19 serological assays to study the immune response to SARS-CoV-2 and vaccines. Calibration of SeroNet serological assays to harmonize results reporting will facilitate future pooled data analyses and study cross-comparisons. IMPORTANCE SeroNet institutions have developed or implemented 61 diverse COVID-19 serological assays and are collaboratively working to harmonize these assays using reference materials to establish standardized reporting units. This will facilitate clinical interpretation of serology results and cross-comparison of research data.
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- 2022
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20. Greater Breadth of Vaccine-Induced Immunity in Females than Males Is Mediated by Increased Antibody Diversity in Germinal Center B Cells
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Rebecca L. Ursin, Santosh Dhakal, Hsuan Liu, Sahana Jayaraman, Han-Sol Park, Harrison R. Powell, Morgan L. Sherer, Kirsten E. Littlefield, Ashley L. Fink, Zexu Ma, Alice L. Mueller, Allison P. Chen, Kumba Seddu, Yishak A. Woldetsadik, Patricia J. Gearhart, H. Benjamin Larman, Robert W. Maul, Andrew Pekosz, and Sabra L. Klein
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sex difference ,antibody response ,H1N1 ,viral immunity ,antigenic drift ,antibody function ,Microbiology ,QR1-502 - Abstract
ABSTRACT Inactivated influenza vaccines induce greater antibody responses in females than males among both humans and mice. To test the breadth of protection, we used recombinant mouse-adapted A/California/2009 (maA/Cal/09) H1N1 viruses containing mutations at one (1M), two (2M), or three (3M) antigenic sites, in addition to a virus containing the 1M mutation and a substitution of the Ca2 antigenic site (Sub) with one derived from an H5 hemagglutinin (HA) to challenge mice of both sexes. Following maA/Cal/09 vaccination, females produced greater virus-specific, class-switched total IgG and IgG2c antibodies against the vaccine and all mutant viruses, and antibodies from females recognized a greater number of unique, linear HA epitopes than did antibodies from males. While females had greater neutralizing antibody titers against the vaccine virus, both sexes showed a lower neutralization capacity against mutant viruses. After virus challenge, vaccinated females had lower pulmonary virus titers and reduced morbidity than males for the 1M and 2M viruses, but not the Sub virus. Females generated greater numbers of germinal center (GC) B cells containing superior somatic hypermutation (SHM) frequencies than vaccinated males. Deletion of activation-induced cytidine deaminase (Aicda) eliminated female-biased immunity and protection against the 2M virus. Harnessing methods to improve GC B cell responses and frequencies of SHM, especially in males, should be considered in the development of universal influenza vaccines. IMPORTANCE Adult females develop greater antibody responses to influenza vaccines than males. We hypothesized that female-biased immunity and protection would be dependent on the extent of virus diversity as well as molecular mechanisms in B cells which constrain the breadth of epitope recognition. We developed a panel of mouse-adapted (ma) A/Cal/09 viruses that had mutations in the immunodominant hemagglutinin. Following vaccination against maA/Cal/09, females were better able to neutralize maA/Cal/09 than males, but neutralization of mutant maA/Cal/09 viruses was equally poor in both sexes, despite vaccinated females being better protected against these viruses. Vaccinated females benefited from the greater production of class-switched, somatically hypermutated antibodies generated in germinal center B cells, which increased recognition of more diverse maA/Cal/09 hemagglutinin antigen epitopes. Female-biased protection against influenza infection and disease after vaccination is driven by differential mechanisms in males versus females and should be considered in the design of novel vaccine platforms.
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- 2022
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21. Implications of Non-Specific Effects for Testing, Approving, and Regulating Vaccines
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Christine Stabell Benn, Nelly Amenyogbe, Anders Björkman, Jorge Domínguez-Andrés, Eleanor N. Fish, Katie L. Flanagan, Sabra L. Klein, Tobias R. Kollmann, Kirsten Ohm Kyvik, Mihai G. Netea, Naja Hulvej Rod, Frederik Schaltz-Buchholzer, Frank Shann, Liisa Selin, Sanne M. Thysen, and Peter Aaby
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Pharmacology ,BCG VACCINATION ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,INFANTS ,DIPHTHERIA-TETANUS-PERTUSSIS ,Toxicology ,MALE MORTALITY ,FEMALE ,POLIO ,All institutes and research themes of the Radboud University Medical Center ,TRIALS ,SEX ,Pharmacology (medical) ,GUINEA-BISSAU ,TITER MEASLES IMMUNIZATION - Abstract
The current framework for testing and regulating vaccines was established before the realization that vaccines, in addition to their effect against the vaccine-specific disease, may also have “non-specific effects” affecting the risk of unrelated diseases. Accumulating evidence from epidemiological studies shows that vaccines in some situations can affect all-cause mortality and morbidity in ways that are not explained by the prevention of the vaccine-targeted disease. Live attenuated vaccines have sometimes been associated with decreases in mortality and morbidity that are greater than anticipated. In contrast, some non-live vaccines have in certain contexts been associated with increases in all-cause mortality and morbidity. The non-specific effects are often greater for female than male individuals. Immunological studies have provided several mechanisms that explain how vaccines might modulate the immune response to unrelated pathogens, such as through trained innate immunity, emergency granulopoiesis, and heterologous T-cell immunity. These insights suggest that the framework for the testing, approving, and regulating vaccines needs to be updated to accommodate non-specific effects. Currently, non-specific effects are not routinely captured in phase I–III clinical trials or in the post-licensure safety surveillance. For instance, an infection with Streptococcus pneumoniae occurring months after a diphtheria-tetanus-pertussis vaccination would not be considered an effect of the vaccination, although evidence indicates it might well be for female individuals. Here, as a starting point for discussion, we propose a new framework that considers the non-specific effects of vaccines in both phase III trials and post-licensure. The current framework for testing and regulating vaccines was established before the realization that vaccines, in addition to their effect against the vaccine-specific disease, may also have "non-specific effects" affecting the risk of unrelated diseases. Accumulating evidence from epidemiological studies shows that vaccines in some situations can affect all-cause mortality and morbidity in ways that are not explained by the prevention of the vaccine-targeted disease. Live attenuated vaccines have sometimes been associated with decreases in mortality and morbidity that are greater than anticipated. In contrast, some non-live vaccines have in certain contexts been associated with increases in all-cause mortality and morbidity. The non-specific effects are often greater for female than male individuals. Immunological studies have provided several mechanisms that explain how vaccines might modulate the immune response to unrelated pathogens, such as through trained innate immunity, emergency granulopoiesis, and heterologous T-cell immunity. These insights suggest that the framework for the testing, approving, and regulating vaccines needs to be updated to accommodate non-specific effects. Currently, non-specific effects are not routinely captured in phase I-III clinical trials or in the post-licensure safety surveillance. For instance, an infection with Streptococcus pneumoniae occurring months after a diphtheria-tetanus-pertussis vaccination would not be considered an effect of the vaccination, although evidence indicates it might well be for female individuals. Here, as a starting point for discussion, we propose a new framework that considers the non-specific effects of vaccines in both phase III trials and post-licensure.
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- 2023
22. Impact of Seasonal Coronavirus Antibodies on Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Responses in Solid Organ Transplant Recipients
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Andrew H Karaba, Weiqiang Zhou, Shuai Li, Tihitina Y Aytenfisu, Trevor S Johnston, Olivia Akinde, Yolanda Eby, Aura T Abedon, Jennifer L Alejo, Caroline X Qin, Elizabeth A Thompson, Jacqueline M Garonzik-Wang, Joel N Blankson, Andrea L Cox, Justin R Bailey, Sabra L Klein, Andrew Pekosz, Dorry L Segev, Aaron A R Tobian, and William A Werbel
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Microbiology (medical) ,Infectious Diseases - Abstract
Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination are reduced in solid organ transplant recipients (SOTRs). We report that increased levels of preexisting antibodies to seasonal coronaviruses are associated with decreased antibody response to SARS-CoV-2 vaccination in SOTRs, supporting that antigenic imprinting modulates vaccine responses in SOTRs.
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- 2022
23. Sex Differences in Active Pulmonary Tuberculosis Outcomes in Mali, West Africa
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Djeneba Dabitao, Amadou Somboro, Ibrahim Sanogo, Bassirou Diarra, Chad J. Achenbach, Jane L. Holl, Bocar Baya, Moumine Sanogo, Mamadou Wague, Nadie Coulibaly, Mahamadou Kone, Hawa Baye Drame, Mohamed Tolofoudie, Bourahima Kone, Ayouba Diarra, Mamadou D. Coulibaly, Kathryn Saliba-Shaw, Yacouba Toloba, Mahamadou Diakite, Seydou Doumbia, Sabra L. Klein, William R. Bishai, Souleymane Diallo, and Robert L. Murphy
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Infectious Diseases ,Virology ,Parasitology - Abstract
Men and women often respond differently to infectious diseases and their treatments. Tuberculosis (TB) is a life-threatening communicable disease that affects more men than women globally. Whether male sex is an independent risk factor for unfavorable TB outcomes, however, has not been rigorously investigated in an African context, where individuals are likely exposed to different microbial and environmental factors. We analyzed data collected from a cohort study in Mali by focusing on newly diagnosed active pulmonary TB individuals who were treatment naive. We gathered baseline demographic, clinical, and microbiologic characteristics before treatment initiation and also at three time points during treatment. More males than females were affected with TB, as evidenced by a male-to-female ratio of 2.4:1. In addition, at baseline, males had a significantly higher bacterial count and shorter time to culture positivity as compared with females. Male sex was associated with lower smear negativity rate after 2 months of treatment also known as the intensive phase of treatment, but not at later time points. There was no relationship between patients’ sex and mortality from any cause during treatment. This study suggests that sex-based differences in TB outcomes exist, with sex-specific effects on disease outcomes being more pronounced before treatment initiation and during the intensive phase of treatment rather than at later phases of treatment.
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- 2022
24. Association of Frailty, Age, and Biological Sex With Severe Acute Respiratory Syndrome Coronavirus 2 Messenger RNA Vaccine–Induced Immunity in Older Adults
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Janna R Shapiro, Ioannis Sitaras, Han Sol Park, Tihitina Y Aytenfisu, Christopher Caputo, Maggie Li, John Lee, Trevor S Johnston, Huifen Li, Camille Wouters, Pricila Hauk, Henning Jacobsen, Yukang Li, Engle Abrams, Steve Yoon, Andrew J Kocot, Tianrui Yang, Yushu Huang, Steven M Cramer, Michael J Betenbaugh, Amanda K Debes, Rosemary Morgan, Aaron M Milstone, Andrew H Karaba, Andrew Pekosz, Sean X Leng, and Sabra L Klein
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Male ,Microbiology (medical) ,Vaccines, Synthetic ,Infectious Diseases ,Frailty ,SARS-CoV-2 ,COVID-19 ,Humans ,Viral Vaccines ,mRNA Vaccines ,Aged - Abstract
Background Male sex and old age are risk factors for severe coronavirus disease 2019, but the intersection of sex and aging on antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has not been characterized. Methods Plasma samples were collected from older adults (aged 75–98 years) before and after 3 doses of SARS-CoV-2 mRNA vaccination, and from younger adults (aged 18–74 years) post-dose 2, for comparison. Antibody binding to SARS-CoV-2 antigens (spike protein [S], S receptor-binding domain, and nucleocapsid), functional activity against S, and live-virus neutralization were measured against the vaccine virus and the Alpha, Delta, and Omicron variants of concern (VOCs). Results Vaccination induced greater antibody titers in older females than in older males, with both age and frailty associated with reduced antibody responses in males but not females. Responses declined significantly in the 6 months after the second dose. The third dose restored functional antibody responses and eliminated disparities caused by sex, age, and frailty in older adults. Responses to the VOCs, particularly the Omicron variant, were significantly reduced relative to the vaccine virus, with older males having lower titers to the VOCs than older females. Older adults had lower responses to the vaccine and VOC viruses than younger adults, with greater disparities in males than in females. Conclusions Older and frail males may be more vulnerable to breakthrough infections owing to low antibody responses before receipt of a third vaccine dose. Promoting third dose coverage in older adults, especially males, is crucial to protecting this vulnerable population.
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- 2022
25. Early Outpatient Treatment for Covid-19 with Convalescent Plasma
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David J. Sullivan, Kelly A. Gebo, Shmuel Shoham, Evan M. Bloch, Bryan Lau, Aarthi G. Shenoy, Giselle S. Mosnaim, Thomas J. Gniadek, Yuriko Fukuta, Bela Patel, Sonya L. Heath, Adam C. Levine, Barry R. Meisenberg, Emily S. Spivak, Shweta Anjan, Moises A. Huaman, Janis E. Blair, Judith S. Currier, James H. Paxton, Jonathan M. Gerber, Joann R. Petrini, Patrick B. Broderick, William Rausch, Marie-Elena Cordisco, Jean Hammel, Benjamin Greenblatt, Valerie C. Cluzet, Daniel Cruser, Kevin Oei, Matthew Abinante, Laura L. Hammitt, Catherine G. Sutcliffe, Donald N. Forthal, Martin S. Zand, Edward R. Cachay, Jay S. Raval, Seble G. Kassaye, E. Colin Foster, Michael Roth, Christi E. Marshall, Anusha Yarava, Karen Lane, Nichol A. McBee, Amy L. Gawad, Nicky Karlen, Atika Singh, Daniel E. Ford, Douglas A. Jabs, Lawrence J. Appel, David M. Shade, Stephan Ehrhardt, Sheriza N. Baksh, Oliver Laeyendecker, Andrew Pekosz, Sabra L. Klein, Arturo Casadevall, Aaron A.R. Tobian, and Daniel F. Hanley
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Adult ,Hospitalization ,Treatment Outcome ,Double-Blind Method ,Ambulatory Care ,Disease Progression ,Immunization, Passive ,COVID-19 ,Humans ,General Medicine ,United States ,COVID-19 Serotherapy - Abstract
Polyclonal convalescent plasma may be obtained from donors who have recovered from coronavirus disease 2019 (Covid-19). The efficacy of this plasma in preventing serious complications in outpatients with recent-onset Covid-19 is uncertain.In this multicenter, double-blind, randomized, controlled trial, we evaluated the efficacy and safety of Covid-19 convalescent plasma, as compared with control plasma, in symptomatic adults (≥18 years of age) who had tested positive for severe acute respiratory syndrome coronavirus 2, regardless of their risk factors for disease progression or vaccination status. Participants were enrolled within 8 days after symptom onset and received a transfusion within 1 day after randomization. The primary outcome was Covid-19-related hospitalization within 28 days after transfusion.Participants were enrolled from June 3, 2020, through October 1, 2021. A total of 1225 participants underwent randomization, and 1181 received a transfusion. In the prespecified modified intention-to-treat analysis that included only participants who received a transfusion, the primary outcome occurred in 17 of 592 participants (2.9%) who received convalescent plasma and 37 of 589 participants (6.3%) who received control plasma (absolute risk reduction, 3.4 percentage points; 95% confidence interval, 1.0 to 5.8; P = 0.005), which corresponded to a relative risk reduction of 54%. Evidence of efficacy in vaccinated participants cannot be inferred from these data because 53 of the 54 participants with Covid-19 who were hospitalized were unvaccinated and 1 participant was partially vaccinated. A total of 16 grade 3 or 4 adverse events (7 in the convalescent-plasma group and 9 in the control-plasma group) occurred in participants who were not hospitalized.In participants with Covid-19, most of whom were unvaccinated, the administration of convalescent plasma within 9 days after the onset of symptoms reduced the risk of disease progression leading to hospitalization. (Funded by the Department of Defense and others; CSSC-004 ClinicalTrials.gov number, NCT04373460.).
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- 2022
26. A Case Study of Two Rodent-Borne Viruses: Not Always the Same Old Suspects
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James E. Childs, Sabra L. Klein, and Gregory E. Glass
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lymphocytic choriomeningitis virus ,Seoul virus ,Rattus norvegicus ,Mus musculus ,zoonotic disease ,Evolution ,QH359-425 ,Ecology ,QH540-549.5 - Abstract
Two Old World rodents, house mice (Mus musculus) and Norway rats (Rattus norvegicus), were introduced into and established populations on every continent, save Antarctica. With their travels, they concomitantly introduced several zoonotic agents capable of causing human diseases. Two viruses—Lymphocytic choriomeningitis virus (LCMV; genus Arenavirus with mice) and Seoul virus (SEOV; genus Hantavirus with rats)—can cause chronic infections within their respective rodent hosts, resulting in persistent or life-long sporadic shedding of virus through secreta and excreta. Although the prevalence of infection within their wild rodent hosts can exceed 25% among mice infected with LCMV and 50% among rats infected with SEOV, acute human disease resulting from direct transmission from wild rodents is rarely reported even though both species live in close coexistence with humans. The usual “classic” zoonotic cycle of transmission from wild rodent reservoirs to humans now includes multiple unusual/unexpected routes. The largest described outbreaks of human disease caused by these viruses are linked to pet rodents. A novel reservoir host, the golden hamster, has supplanted house mice as the major source of LCMV infection, and SEOV outbreaks are linked to fancy rats kept as pets. Following LCMV, and to a lesser extent SEOV, outbreaks or infections associated with lab animals and/or cultured tissues derived from mice and hamsters have led to hundreds of cases of LCMV among laboratory workers, and SEOV has been detected among cell-cultured tissues. Additionally, LCMV is now a recognized source of severe congenital disease and is the unexpected source of severe and often fatal disease among solid organ recipients. Although the extensive usual and unusual routes of LCMV infection are exceptional there are many parallels with SEOV emergence.
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- 2019
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27. Antibody Correlates of Protection for COVID-19 Convalescent Plasma Associated with Reduced Outpatient Hospitalizations
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Han-Sol Park, Caelan Barranta, Anna Yin, John S. Lee, Christopher A. Caputo, Maggie Li, Steve Yoon, Ioannis Sitaras, Anne Jedlicka, Yolanda Eby, Malathi Ram, Reinaldo E. Fernandez, Owen R. Baker, Aarthi G. Shenoy, Giselle S. Mosnaim, Yuriko Fukuta, Bela Patel, Sonya L. Heath, Adam C. Levine, Barry R. Meisenberg, Emily S. Spivak, Shweta Anjan, Moises A. Huaman, Janis E. Blair, Judith S. Currier, James H. Paxton, Jonathan M. Gerber, Joann R. Petrini, Patrick B. Broderick, William Rausch, Marie Elena Cordisco, Jean Hammel, Benjamin Greenblatt, Valerie C. Cluzet, Daniel Cruser, Kevin Oei, Matthew Abinante, Laura L. Hammitt, Catherine G. Sutcliffe, Donald N. Forthal, Martin S. Zand, Edward R. Cachay, Jay S. Raval, Seble G. Kassaye, Christi E. Marshall, Anusha Yarava, Karen Lane, Nichol A. McBee, Amy L. Gawad, Nicky Karlen, Atika Singh, Daniel E. Ford, Douglas A. Jabs, Lawrence J. Appel, David M. Shade, Bryan Lau, Stephan Ehrhardt, Sheriza N. Baksh, Janna R. Shapiro, Jiangda Ou, Thomas J. Gniadek, Patrizio Caturegli, Jinke Wu, Nelson Ndahiro, Michael J. Betenbaugh, Alyssa Ziman, Daniel F. Hanley, Arturo Casadevall, Shmuel Shoham, Evan M. Bloch, Kelly A. Gebo, Aaron A.R. Tobian, Oliver Laeyendecker, Andrew Pekosz, Sabra L. Klein, and David J. Sullivan
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Article - Abstract
SARS-CoV-2 antibody levels associated with reduced hospitalization risk remain undefined. Our outpatient COVID-19 convalescent plasma (CCP), placebo-controlled trial observed SARS-CoV-2 antibody levels decreasing 22-fold from matched donor units into post-transfusion seronegative recipients. Unvaccinated recipients were jointly stratified by a) early or late transfusion (≤ 5 or >5 days from symptom onset) and b) high or low post-transfusion SARS-CoV-2 antibody levels (< or ≥ geometric mean). Early treatment with high post-transfusion antibody levels reduced hospitalization risk-0/102 (0%) compared to all other CCP recipients-17/370 (4.6%; Fisher exact p=0.03) and to all control plasma recipients-35/461 (7.6%; Fisher exact p=0.001). A similar donor upper/lower antibody level and early late transfusion stratified analyses indicated significant hospital risk reduction. Pre-transfusion nasal viral loads were similar in CCP and control recipients regardless of hospitalization outcome. Therapeutic CCP should comprise the upper 30% of donor antibody levels to provide effective outpatient use for immunocompromised and immunocompetent outpatients.
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- 2023
28. Adverse outcomes in SARS-CoV-2 infected pregnant mice are gestational age-dependent and resolve with antiviral treatment
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Patrick S. Creisher, Jamie L. Perry, Weizhi Zhong, Jun Lei, Kathleen R Mulka, Hurley Ryan, Ruifeng Zhou, Elgin H. Akin, Anguo Liu, Wayne Mitzner, Irina Burd, Andrew Pekosz, and Sabra L. Klein
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Article - Abstract
SARS-CoV-2 infection during pregnancy is associated with severe COVID-19 and adverse fetal outcomes, but the underlying mechanisms remain poorly understood. Moreover, clinical studies assessing therapeutics against SARS-CoV-2 in pregnancy are limited. To address these gaps, we developed a mouse model of SARS-CoV-2 infection during pregnancy. Outbred CD1 mice were infected at embryonic day (E) 6, E10, or E16 with a mouse adapted SARS-CoV-2 (maSCV2) virus. Outcomes were gestational age-dependent with greater morbidity, reduced pulmonary function, reduced anti-viral immunity, greater viral titers, and more adverse fetal outcomes occurring with infection at E16 (3rdtrimester-equivalent) than with infection at either E6 (1sttrimester-equivalent) or E10 (2ndtrimester-equivalent). To assess the efficacy of ritonavir-boosted nirmatrelvir (recommended for pregnant individuals with COVID- 19), we treated E16-infected dams with mouse equivalent doses of nirmatrelvir and ritonavir. Treatment reduced pulmonary viral titers, decreased maternal morbidity, and prevented adverse offspring outcomes. Our results highlight that severe COVID-19 during pregnancy and adverse fetal outcomes are associated with heightened virus replication in maternal lungs. Ritonavir- boosted nirmatrelvir mitigated adverse maternal and fetal outcomes of SARS-CoV-2 infection. These findings prompt the need for further consideration of pregnancy in preclinical and clinical studies of therapeutics against viral infections.
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- 2023
29. Reduced control of SARS-CoV-2 infection is associated with lower mucosal antibody responses in pregnant women
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Laura A. St Clair, Raghda E. Eldesouki, Jaiprasath Sachithanandham, Anna Yin, Amary Fall, C. Paul Morris, Julie M. Norton, Michael Forman, Omar Abdullah, Santosh Dhakal, Caelan Barranta, Hana Golding, Susan J. Bersoff-Matcha, Catherine Pilgrim-Grayson, Leah Berhane, Andrea L. Cox, Irina Burd, Andrew Pekosz, Heba H. Mostafa, Eili Y. Klein, and Sabra L. Klein
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Article - Abstract
ImportancePregnant women are at increased risk of severe COVID-19, but the contribution of viral RNA load, the presence of infectious virus, and mucosal antibody responses remain understudied.ObjectiveTo evaluate the association of COVID-19 outcomes following confirmed infection with vaccination status, mucosal antibody responses, infectious virus recovery and viral RNA levels in pregnant compared with non-pregnant women.DesignA retrospective observational cohort study of remnant clinical specimens from SARS-CoV-2 infected patients between October 2020-May 2022.SettingFive acute care hospitals within the Johns Hopkins Health System (JHHS) in the Baltimore, MD-Washington, DC area.ParticipantsParticipants included confirmed SARS-CoV-2 infected pregnant women and matched non-pregnant women (matching criteria included age, race/ethnicity, and vaccination status).ExposureSARS-CoV-2 infection, with documentation of SARS-CoV-2 mRNA vaccination.Main Outcome(s)The primary dependent measures were clinical COVID-19 outcomes, infectious virus recovery, viral RNA levels, and mucosal anti-spike (S) IgG titers from upper respiratory tract samples. Clinical outcomes were compared using odds ratios (OR), and measures of virus and antibody were compared using either Fisher’s exact test, two-way ANOVA, or regression analyses. Results were stratified according to pregnancy, vaccination status, maternal age, trimester of pregnancy, and infecting SARS-CoV-2 variant.Results(s)A total of 452 individuals (117 pregnant and 335 non-pregnant) were included in the study, with both vaccinated and unvaccinated individuals represented. Pregnant women were at increased risk of hospitalization (OR = 4.2; CI = 2.0-8.6), ICU admittance, (OR = 4.5; CI = 1.2-14.2), and of being placed on supplemental oxygen therapy (OR = 3.1; CI =1.3-6.9). An age-associated decrease in anti-S IgG titer and corresponding increase in viral RNA levels (P< 0.001) was observed in vaccinated pregnant, but not non-pregnant, women. Individuals in their 3rdtrimester had higher anti-S IgG titers and lower viral RNA levels (P< 0.05) than those in their 1stor 2ndtrimesters. Pregnant individuals experiencing breakthrough infections due to the omicron variant had reduced anti-S IgG compared to non-pregnant women (P< 0.05).Conclusions and RelevanceIn this cohort study, vaccination status, maternal age, trimester of pregnancy, and infecting SARS-CoV-2 variant were each identified as drivers of differences in mucosal anti-S IgG responses in pregnant compared with non-pregnant women. Observed increased severity of COVID-19 and reduced mucosal antibody responses particularly among pregnant participants infected with the Omicron variant suggest that maintaining high levels of SARS-CoV-2 immunity may be important for protection of this at-risk population.Key PointsQuestionIs greater COVID-19 disease severity during pregnancy associated with either reduced mucosal antibody responses to SARS-CoV-2 or increased viral RNA levels?FindingIn a retrospective cohort of pregnant and non-pregnant women with confirmed SARS-CoV-2 infection, we observed that (1) disease severity, including ICU admission, was greater among pregnant than non-pregnant women; (2) vaccination was associated with reduced recovery of infectious virus in non-pregnant women but not in pregnant women; (3) increased nasopharyngeal viral RNA levels were associated with reduced mucosal IgG antibody responses in pregnant women; and (4) greater maternal age was associated with reduced mucosal IgG responses and increased viral RNA levels, especially among women infected with the Omicron variant.MeaningThe findings of this study provide novel evidence that, during pregnancy, lower mucosal antibody responses are associated with reduced control of SARS-CoV-2, including variants of concern, and greater disease severity, especially with increasing maternal age. Reduced mucosal antibody responses among vaccinated pregnant women highlight the need for bivalent booster doses during pregnancy.
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- 2023
30. Persistent SARS-CoV-2–specific immune defects in kidney transplant recipients following third mRNA vaccine dose
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William A. Werbel, Andrew H. Karaba, Teresa Po-Yu Chiang, Allan B. Massie, Diane M. Brown, Natasha Watson, Maggie Chahoud, Elizabeth A. Thompson, Aileen C. Johnson, Robin K. Avery, Willa V. Cochran, Daniel Warren, Tao Liang, Miguel Fribourg, Christopher Huerta, Hady Samaha, Sabra L. Klein, Maria P. Bettinotti, William A. Clarke, Ioannis Sitaras, Nadine Rouphael, Andrea L. Cox, Justin R. Bailey, Andrew Pekosz, Aaron A.R. Tobian, Christine M. Durand, Nancy D. Bridges, Christian P. Larsen, Peter S. Heeger, and Dorry L. Segev
- Subjects
Transplantation ,Immunology and Allergy ,Pharmacology (medical) - Published
- 2023
31. The intersection of biological sex and gender in adverse events following seasonal influenza vaccination in older adults
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Janna R. Shapiro, Kumba Seddu, Han-Sol Park, John S. Lee, Patrick S. Creisher, Anna Yin, Patrick Shea, Helen Kuo, Huifen Li, Engle Abrams, Sean X. Leng, Rosemary Morgan, and Sabra L. Klein
- Abstract
Background Women/females report more adverse events (AE) following immunization than men/males for many vaccines, including the influenza and COVID-19 vaccines. This discrepancy is often dismissed as a reporting bias, yet the relative contributions of biological sex and gender are poorly understood. We investigated the roles of sex and gender in the rate of AE following administration of the high-dose seasonal influenza vaccine to older adults (≥ 75 years) using an AE questionnaire administered 5–8 days post-vaccination. Participant sex (male or female) was determined by self-report and a gender score questionnaire was used to assign participants to one of four gender categories (feminine, masculine, androgynous, or undifferentiated). Sex steroid hormones and inflammatory cytokines were measured in plasma samples collected prior to vaccination to elucidate a possible biological mechanism for the AE reported. Results A total of 423 vaccines were administered to 173 participants over four influenza seasons (2019-22) and gender data were available for 339 of these vaccinations (2020-22). At least one AE was reported following 105 vaccinations (25%), by 23 males and 82 females. The majority of AE occurred at the site of injection, were mild, and transient. The odds of experiencing an AE were 3-fold greater in females than males and decreased with age to a greater extent in females than males. The effects of gender, however, were not statistically significant, supporting a central role of biological sex in the occurrence of AE. In males, estradiol was significantly associated with IL-6 and with the probability of experiencing an AE. Both associations were absent in females, suggesting a sex-specific effect of estradiol on the occurrence of AE that supports the finding of a biological sex difference. Conclusions These data support a larger role for biological sex than for gender in the occurrence of AE following influenza vaccination in older adults and provide an initial investigation of hormonal mechanisms that may mediate this sex difference. This study highlights the complexities of measuring gender and the importance of assessing AE separately for males and females to better understand how vaccination strategies can be tailored to different subsets of the population.
- Published
- 2023
32. A Fourth Dose of COVID-19 Vaccine Does Not Induce Neutralization of the Omicron Variant Among Solid Organ Transplant Recipients With Suboptimal Vaccine Response
- Author
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Andrew H. Karaba, Trevor S. Johnston, Tihitina Y. Aytenfisu, Olivia Akinde, Yolanda Eby, Jessica E. Ruff, Aura T. Abedon, Jennifer L. Alejo, Joel N. Blankson, Andrea L. Cox, Justin R. Bailey, Sabra L. Klein, Andrew Pekosz, Dorry L. Segev, Aaron A.R. Tobian, and William A. Werbel
- Subjects
Transplantation ,COVID-19 Vaccines ,SARS-CoV-2 ,Immunoglobulin G ,Immunization, Secondary ,COVID-19 ,Humans ,Antibodies, Viral ,Antibodies, Neutralizing ,Transplant Recipients - Abstract
Humoral responses to coronavirus disease 2019 (COVID-19) vaccines are attenuated in solid organ transplant recipients (SOTRs), necessitating additional booster vaccinations. The Omicron variant demonstrates substantial immune evasion, and it is unknown whether additional vaccine doses increase neutralizing capacity versus this variant of concern (VOC) among SOTRs.Within an observational cohort, 25 SOTRs with low seroresponse underwent anti-severe acute respiratory syndrome coronavirus 2 spike and receptor-binding domain immunoglobulin (Ig)G testing using a commercially available multiplex ELISA before and after a fourth COVID-19 vaccine dose (D4). Surrogate neutralization (percent angiotensin-converting enzyme 2 inhibition [%ACE2i], range 0%-100% with20% correlating with live virus neutralization) was measured against full-length spike proteins of the vaccine strain and 5 VOCs including Delta and Omicron. Changes in IgG level and %ACE2i were compared using the paired Wilcoxon signed-rank test.Anti-receptor-binding domain and anti-spike seropositivity increased post-D4 from 56% to 84% and 68% to 88%, respectively. Median (interquartile range) anti-spike antibody significantly increased post-D4 from 42.3 (4.9-134.2) to 228.9 (1115.4-655.8) World Health Organization binding antibody units. %ACE2i (median [interquartile range]) also significantly increased against the vaccine strain (5.8% [0%-16.8%] to 20.6% [5.8%-45.9%]) and the Delta variant (9.1% [4.9%-12.8%] to 17.1% [10.3%-31.7%]), yet neutralization versus Omicron was poor, did not increase post-D4 (4.1% [0%-6.9%] to 0.5% [0%-5.7%]), and was significantly lower than boosted healthy controls.Although a fourth vaccine dose increases anti-spike IgG and neutralizing capacity against many VOCs, some SOTRs may remain at high risk for Omicron infection despite boosting. Thus, additional protective interventions or alternative vaccination strategies should be urgently explored.
- Published
- 2022
33. Female-biased effects of aging on a chimeric hemagglutinin stalk-based universal influenza virus vaccine in mice
- Author
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Sharvari Deshpande, Santosh Dhakal, Florian Krammer, Sabra L. Klein, Meagan McMahon, and Shirin Strohmeier
- Subjects
Male ,030231 tropical medicine ,Hemagglutinin (influenza) ,Hemagglutinin Glycoproteins, Influenza Virus ,Antibodies, Viral ,medicine.disease_cause ,Article ,Virus ,Mice ,03 medical and health sciences ,Influenza A Virus, H1N1 Subtype ,Sex Factors ,0302 clinical medicine ,Orthomyxoviridae Infections ,Immunity ,Influenza, Human ,Influenza A virus ,medicine ,Animals ,Humans ,030212 general & internal medicine ,Young adult ,Hemagglutination assay ,General Veterinary ,General Immunology and Microbiology ,biology ,business.industry ,Age Factors ,Public Health, Environmental and Occupational Health ,Antibodies, Neutralizing ,Mice, Inbred C57BL ,Disease Models, Animal ,Titer ,Hemagglutinins ,Infectious Diseases ,Influenza Vaccines ,Immunology ,biology.protein ,Molecular Medicine ,Female ,Antibody ,business - Abstract
To determine if biological sex and age intersect to affect universal influenza vaccine-induced immunity, adult and aged male and female C57BL/6 mice were sequentially immunized with a chimeric-hemagglutinin (cHA) stalk-based H1 vaccine. Adult mice developed greater quantity and quality of H1-stalk antibodies, that were more cross-reactive with other group 1, but not group 2, influenza viruses, than aged mice. The vaccine did not induce neutralizing or hemagglutination inhibition antibodies, but rather antibody-dependent cellular cytotoxicity, which was greater in adult than aged mice. Vaccinated adult mice were better protected than aged mice after challenge with 2009 H1N1 virus, experiencing less morbidity and having lower pulmonary virus titers. The age-associated decline in immunity and protection was consistently greater among females than males, with the reduction in immunity and protection for aged as compared with adult females often being the sole comparison driving the overall age-associated significant differences. The age-associated reduction in stalk-based immunity in females was not, however, associated with changes in estradiol. To determine if the better antibodies in adults could be utilized to protect aged mice, serum was passively transferred from vaccinated adult mice into naïve sex-matched aged mice. Even with transferred serum from young adult mice, aged females still suffered greater morbidity than aged males. These data suggest there are sex-dependent effects of aging on cHA-based universal influenza virus vaccine-induced immunity that cannot be reversed through transfer of serum from young animals. The lack of consideration of sex-specific effects of aging on immunity could hinder efforts toward universal vaccines.
- Published
- 2022
34. A bacterial extracellular vesicle-based intranasal vaccine against SARS-CoV-2 protects against disease and elicits neutralizing antibodies to wild-type and Delta variants
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Linglei Jiang, Tom A.P. Driedonks, Wouter S.P. Jong, Santosh Dhakal, H. Bart van den Berg van Saparoea, Ioannis Sitaras, Ruifeng Zhou, Christopher Caputo, Kirsten Littlefield, Maggie Lowman, Mengfei Chen, Gabriela Lima, Olesia Gololobova, Barbara Smith, Vasiliki Mahairaki, M. Riley Richardson, Kathleen R. Mulka, Andrew P. Lane, Sabra L. Klein, Andrew Pekosz, Cory F. Brayton, Joseph L. Mankowski, Joen Luirink, Jason S. Villano, Kenneth W. Witwer, Molecular Microbiology, AIMMS, and LaserLaB - Molecular Biophysics
- Subjects
Delta variant ,Histology ,COVID-19 Vaccines ,exosomes ,medicine.disease_cause ,Virus ,SDG 3 - Good Health and Well-being ,medicine ,Animals ,Humans ,Neutralizing antibody ,Coronavirus ,Mammals ,biology ,SARS-CoV-2 ,Bacterial extracellular vesicle ,COVID-19 ,Viral Vaccines ,Cell Biology ,vaccines ,biology.organism_classification ,Antibodies, Neutralizing ,Virology ,Vaccination ,Immunization ,Liposomes ,biology.protein ,Nanoparticles ,Antibody ,extracellular vesicles ,Mesocricetus ,outer membrane vesicles - Abstract
Several vaccines have been introduced to combat the coronavirus infectious disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current SARS-CoV-2 vaccines include mRNA-containing lipid nanoparticles or adenoviral vectors that encode the SARS-CoV-2 Spike (S) protein of SARS-CoV-2, inactivated virus, or protein subunits. Despite growing success in worldwide vaccination efforts, additional capabilities may be needed in the future to address issues such as stability and storage requirements, need for vaccine boosters, desirability of different routes of administration, and emergence of SARS-CoV-2 variants such as the Delta variant. Here, we present a novel, well-characterized SARS-CoV-2 vaccine candidate based on extracellular vesicles (EVs) of Salmonella typhimurium that are decorated with the mammalian cell culture-derived Spike receptor-binding domain (RBD). RBD-conjugated outer membrane vesicles (RBD-OMVs) were used to immunize the golden Syrian hamster (Mesocricetus auratus) model of COVID-19. Intranasal immunization resulted in high titers of blood anti-RBD IgG as well as detectable mucosal responses. Neutralizing antibody activity against wild-type and Delta variants was evident in all vaccinated subjects. Upon challenge with live virus, hamsters immunized with RBD-OMV, but not animals immunized with unconjugated OMVs or a vehicle control, avoided body mass loss, had lower virus titers in bronchoalveolar lavage fluid, and experienced less severe lung pathology. Our results emphasize the value and versatility of OMV-based vaccine approaches.
- Published
- 2022
35. Sex-specific effects of age and body mass index on antibody responses to seasonal influenza vaccines in healthcare workers
- Author
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Kathryn Shaw-Saliba, Janna R. Shapiro, Patrick Shea, Rebecca L. Ursin, Rosemary Morgan, Helen Kuo, Ashley L. Fink, Hsuan Lui, Andrew Pekosz, Kristyn E. Sylvia, Sabra L. Klein, Jason W. Westerbeck, Katherine J. Fenstermacher, Han Sol Park, Santosh Dhakal, and Richard E. Rothman
- Subjects
Male ,Influenza vaccine ,Health Personnel ,030231 tropical medicine ,Population ,Antibodies, Viral ,Article ,Body Mass Index ,03 medical and health sciences ,Influenza A Virus, H1N1 Subtype ,0302 clinical medicine ,Influenza, Human ,medicine ,Humans ,030212 general & internal medicine ,Seroconversion ,education ,education.field_of_study ,General Veterinary ,General Immunology and Microbiology ,business.industry ,Influenza A Virus, H3N2 Subtype ,Vaccination ,Public Health, Environmental and Occupational Health ,virus diseases ,medicine.disease ,Vaccine efficacy ,Obesity ,Titer ,Cross-Sectional Studies ,Infectious Diseases ,Influenza Vaccines ,Antibody Formation ,Molecular Medicine ,Female ,Seasons ,business ,Body mass index ,Demography - Abstract
Healthcare institutions with mandatory influenza vaccination policies have over 90% vaccination rates among healthcare workers (HCWs) resulting in a population that has received the influenza vaccine in many, consecutive years. This study explored the impact of sex and other host factors in pre- and post-vaccination neutralizing antibody (nAb) titers and seroconversion against the H1N1 and H3N2 influenza A viruses (IAVs) among HCWs enrolled into a cross-sectional serosurvey during the annual Johns Hopkins Hospital employee vaccination campaign in the 2017–18 and 2018–19 seasons. The study enrolled 111 participants (male = 38, female = 73) in 2017–18 and 163 (male = 44, female = 119) in 2018–19. Serum samples were collected immediately prior to vaccination and approximately 28 days later and nAb titers to vaccine strains determined. An intersectional approach was used to disaggregate the combined effects of sex with age and body mass index (BMI) in the nAb response. Differences between the pre- or post-vaccination geometric mean nAb titers between male and female HCWs were not observed. Male HCWs were 2.86 times more likely to seroconvert compared to female HCWs in 2017–2018, but the same trend was not observed in the following year. When data were disaggregated by age and sex, older female HCWs had higher H1N1 pre- and post-vaccination nAb titers compared to male HCWs in the same age group for both vaccination campaign seasons. In both years, the decline in H3N2 pre-vaccination titers with increasing BMI was greater in female than male HCW. The sex-specific effects of age and BMI on nAb responses to seasonal influenza vaccines require greater consideration.
- Published
- 2022
36. Methodological approaches to optimize multiplex oral fluid SARS-CoV-2 IgG assay performance and correlation with serologic and neutralizing antibody responses
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Nora Pisanic, Annukka A. R. Antar, Kate Kruczynski, Magdielis Gregory Rivera, Santosh Dhakal, Kristoffer Spicer, Pranay R. Randad, Andrew Pekosz, Sabra L. Klein, Michael J. Betenbaugh, Barbara Detrick, William Clarke, David L. Thomas, Yukari C. Manabe, and Christopher D. Heaney
- Subjects
Immunology ,Immunology and Allergy ,Article - Abstract
BackgroundOral fluid (hereafter, saliva) is a non-invasive and attractive alternative to blood for SARS-CoV-2 IgG testing; however, the heterogeneity of saliva as a matrix poses challenges for immunoassay performance.ObjectivesTo optimize performance of a magnetic microparticle-based multiplex immunoassay (MIA) for SARS-CoV-2 IgG measurement in saliva, with consideration of: i) threshold setting and validation across different MIA bead batches; ii) sample qualification based on salivary total IgG concentration; iii) calibration to U.S. SARS-CoV-2 serological standard binding antibody units (BAU); and iv) correlations with blood-based SARS-CoV-2 serological and neutralizing antibody (nAb) assays.MethodsThe salivary SARS-CoV-2 IgG MIA included 2 nucleocapsid (N), 3 receptor-binding domain (RBD), and 2 spike protein (S) antigens. Gingival crevicular fluid (GCF) swab saliva samples were collected before December, 2019 (n=555) and after molecular test-confirmed SARS-CoV-2 infection from 113 individuals (providing up to 5 repeated-measures; n=398) and used to optimize and validate MIA performance (total n=953). Combinations of IgG responses to N, RBD and S and total salivary IgG concentration (μg/mL) as a qualifier of nonreactive samples were optimized and validated, calibrated to the U.S. SARS-CoV-2 serological standard, and correlated with blood-based SARS-CoV-2 IgG ELISA and nAb assays.ResultsThe sum of signal to cutoff (S/Co) to all seven MIA SARS-CoV-2 antigens and disqualification of nonreactive saliva samples with ≤15 μg/mL total IgG led to correct classification of 62/62 positives (sensitivity [Se]=100.0%; 95% confidence interval [CI]=94.8%, 100.0%) and 108/109 negatives (specificity [Sp]=99.1%; 95% CI=97.3%, 100.0%) at 8-million beads coupling scale and 80/81 positives (Se=98.8%; 95% CI=93.3%, 100.0%] and 127/127 negatives (Sp=100%; 95% CI=97.1%, 100.0%) at 20-million beads coupling scale. Salivary SARS-CoV-2 IgG crossed the MIA cutoff of 0.1 BAU/mL on average 9 days post-COVID-19 symptom onset and peaked around day 30. Among n=30 matched saliva and plasma samples, salivary SARS-CoV-2 MIA IgG levels correlated with corresponding-antigen plasma ELISA IgG (N: ρ=0.67, RBD: ρ=0.76, S: ρ=0.82; allpppConclusionsA salivary SARS-CoV-2 IgG MIA produced consistently high Se (>98.8%) and Sp (>99.1%) across two bead coupling scales and correlations with nAb responses that were similar to blood-based SARS-CoV-2 IgG ELISA data. This non-invasive salivary SARS-CoV-2 IgG MIA could increase engagement of vulnerable populations and improve broad understanding of humoral immunity (kinetics and gaps) within the evolving context of booster vaccination, viral variants and waning immunity.
- Published
- 2022
37. Reconsideration of Antinucleocapsid IgG Antibody as a Marker of SARS-CoV-2 Infection Postvaccination for Mild COVID-19 Patients
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Santosh Dhakal, Tong Yu, Anna Yin, Nora Pisanic, Zoe O Demko, Annukka A R Antar, Andrea L Cox, Christopher D Heaney, Yukari C Manabe, and Sabra L Klein
- Subjects
Infectious Diseases ,Oncology ,Brief Report - Abstract
Antinucleocapsid (anti-N) immunoglobulin G antibody responses were lower in plasma and oral fluid after severe acute respiratory syndrome coronavirus 2 infection in vaccinated patients compared with patients infected before vaccination or infected without vaccination. This raises questions about the long-term use of anti-N antibodies as a marker for natural infection for surveillance.
- Published
- 2022
38. The Association between Hantavirus Infection and Selenium Deficiency in Mainland China
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Li-Qun Fang, Marco Goeijenbier, Shu-Qing Zuo, Li-Ping Wang, Song Liang, Sabra L. Klein, Xin-Lou Li, Kun Liu, Lu Liang, Peng Gong, Gregory E. Glass, Eric van Gorp, Jan H. Richardus, Jia-Qi Ma, Wu-Chun Cao, and Sake J. de Vlas
- Subjects
hemorrhagic fever with renal syndrome ,selenium ,hantavirus ,rodents ,environmental factors ,China ,Microbiology ,QR1-502 - Abstract
Hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses and transmitted by rodents is a significant public health problem in China, and occurs more frequently in selenium-deficient regions. To study the role of selenium concentration in HFRS incidence we used a multidisciplinary approach combining ecological analysis with preliminary experimental data. The incidence of HFRS in humans was about six times higher in severe selenium-deficient and double in moderate deficient areas compared to non-deficient areas. This association became statistically stronger after correction for other significant environment-related factors (low elevation, few grasslands, or an abundance of forests) and was independent of geographical scale by separate analyses for different climate regions. A case-control study of HFRS patients admitted to the hospital revealed increased activity and plasma levels of selenium binding proteins while selenium supplementation in vitro decreased viral replication in an endothelial cell model after infection with a low multiplicity of infection (MOI). Viral replication with a higher MOI was not affected by selenium supplementation. Our findings indicate that selenium deficiency may contribute to an increased prevalence of hantavirus infections in both humans and rodents. Future studies are needed to further examine the exact mechanism behind this observation before selenium supplementation in deficient areas could be implemented for HFRS prevention.
- Published
- 2015
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39. Influenza subtype-specific maternal antibodies protect offspring against infection but inhibit vaccine-induced immunity and protection in mice
- Author
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Patrick S. Creisher, Ariana D. Campbell, Jamie L. Perry, Katerina Roznik, Irina Burd, and Sabra L. Klein
- Subjects
Male ,General Veterinary ,General Immunology and Microbiology ,Public Health, Environmental and Occupational Health ,Antibodies, Viral ,Article ,Mice ,Infectious Diseases ,Influenza A Virus, H1N1 Subtype ,Orthomyxoviridae Infections ,Pregnancy ,Influenza Vaccines ,Influenza A virus ,Influenza, Human ,Molecular Medicine ,Animals ,Humans ,Female - Abstract
Following influenza A virus (IAV) infection or vaccination during pregnancy, maternal antibodies are transferred to offspring in utero and during lactation. The age and sex of offspring may differentially impact the transfer and effects of maternal immunity on offspring. To evaluate the effects of maternal IAV infection on immunity in offspring, we intranasally inoculated pregnant mice with sublethal doses of mouse-adapted (ma) H1N1, maH3N2, or media (mock) at embryonic day 10. In offspring of IAV-infected dams, maternal subtype-specific antibodies peaked at postnatal day (PND) 23, remained detectable through PND 50, and were undetectable by PND 105 in both sexes. When offspring were challenged with homologous IAV at PND 23, both male and female offspring had greater clearance of pulmonary virus and less morbidity and mortality than offspring from mock-inoculated dams. Inactivated influenza vaccination (IIV) against homologous IAV at PND 23 caused lower vaccine-induced antibody responses and protection following live virus challenge in offspring from IAV than mock-infected dams, with this effect being more pronounced among female than male offspring. At PND 105, there was no impact of maternal infection status, but vaccination induced greater antibody responses and protection against challenge in female than male offspring of both IAV-infected and mock-inoculated dams. To determine if maternal antibody or infection interfered with vaccine-induced immunity and protection in early life, offspring were vaccinated and challenged against a heterosubtypic IAV (i.e., different IAV group than dam) at PND 23 or 105. Heterosubtypic IAV maternal immunity did not affect antibody responses after IIV or protection after live IAV challenge of vaccinated offspring at either age. Subtype-specific maternal IAV antibodies, therefore, provide protection independent of offspring sex but interfere with vaccine-induced immunity and protection in offspring with more pronounced effects among females than males.
- Published
- 2022
40. Of mice, men, women, and cancer
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Alice L. Mueller and Sabra L. Klein
- Subjects
Male ,Mice ,Infectious Diseases ,Neoplasms ,Immunology ,Immunology and Allergy ,Animals ,Humans ,Cell Differentiation ,Female ,CD8-Positive T-Lymphocytes - Abstract
The prevalence and severity of cancers in non-reproductive tissues are greater in males than females, but the sex-specific factors contributing to this remain ill described. In this issue of Immunity, Yang et al. (2022) uncover a mechanism of androgen signaling leading to an exhausted, terminally differentiated CD8
- Published
- 2022
41. The immune phenotype of perinatal anxiety
- Author
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Morgan L. Sherer, Kristin M. Voegtline, Han-Sol Park, Kristen N. Miller, Lauren C. Shuffrey, Sabra L. Klein, and Lauren M. Osborne
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Behavioral Neuroscience ,Phenotype ,Endocrine and Autonomic Systems ,Pregnancy ,Immunology ,Leukocytes, Mononuclear ,Cytokines ,Humans ,Female ,Anxiety ,Biomarkers - Abstract
Immune dysregulation has been linked to both psychiatric illness and pregnancy morbidity, including perinatal depression, but little is known about the immune phenotype of perinatal anxiety. Here, we sought to identify the unique immune profile of antenatal anxiety.Pregnant women (n = 107) were followed prospectively at 2nd and 3rd trimesters (T2, T3) and 6 weeks postpartum (PP6). Each visit included a blood draw and psychological evaluation, with clinical anxiety assessed using the Spielberg State-Trait Anxiety Scale. We enrolled both healthy controls and participants with anxiety alone; those with comorbid depression were excluded. Multiplex cytokine assays and flow cytometry were used to examine the association of anxiety symptoms with secreted immune markers and PBMC-derived immune cells.K cluster means revealed three clusters of anxiety symptomatology; due to low numbers in the highest severity anxiety group, these were collapsed into two groups: Non-Anxiety and Anxiety. Principal components analysis revealed two distinct clusters of cytokine secretion including one cluster that consisted of many innate immune cytokines and differed between groups. Compared to women in the Non-Anxiety group, women in the Anxiety group had lower levels of cytokine expression during pregnancy and an increase in levels into the postpartum, whereas Non-Anxiety women experienced a time-dependent decline. Immune cell populations also differed between our two groups, with the Anxiety group showing a decrease in the ratio of B cells to T cells from pregnancy to postpartum, whereas the Non-Anxiety women showed an increase in this ratio over time. Women in the Anxiety group also demonstrated an increased ratio of cytotoxic to helper T cells throughout pregnancy, a modest increase in the Th1:Th2 ratio across pregnancy, and a lower ratio of Th17:TThese data suggest that the immune response throughout the antenatal period differs for women with anxiety symptoms compared to those without, suggestive of a unique immune phenotype of perinatal anxiety.
- Published
- 2022
42. Downregulation of transcriptional activity, increased inflammation, and damage in the placenta following
- Author
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Patrick S, Creisher, Jun, Lei, Morgan L, Sherer, Amanda, Dziedzic, Anne E, Jedlicka, Harish, Narasimhan, Anna, Chudnovets, Ariana D, Campbell, Anguo, Liu, Andrew, Pekosz, Irina, Burd, and Sabra L, Klein
- Abstract
Zika virus (ZIKV) infection during pregnancy causes serious adverse outcomes to the developing fetus, including fetal loss and birth defects known as congenital Zika syndrome (CZS). The mechanism by which ZIKV infection causes these adverse outcomes and specifically, the interplay between the maternal immune response and ZIKV replication has yet to be fully elucidated. Using an immunocompetent mouse model of transplacental ZIKV transmission and adverse pregnancy outcomes, we have previously shown that Asian lineage ZIKV disrupts placental morphology and induces elevated secretion of IL-1β. In the current manuscript, we characterized placental damage and inflammation during
- Published
- 2022
43. Editorial: Differential Efficacy of Immune Checkpoint Inhibitors due to Age and Sex Factors
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Pei Pei Chong, Joshua B. Rubin, Maha Abdullah, Fabio Conforti, Sabra L. Klein, and Wanli Liu
- Subjects
Antineoplastic Agents, Immunological ,Sex Factors ,Immunology ,Immunology and Allergy ,Immunotherapy ,Immune Checkpoint Inhibitors - Published
- 2022
44. Genetic and hormonal mechanisms underlying sex-specific immune responses in tuberculosis
- Author
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Manish Gupta, Geetha Srikrishna, Sabra L. Klein, and William R. Bishai
- Subjects
Male ,Immunology ,Immunity ,Immunology and Allergy ,Animals ,Humans ,Tuberculosis ,Female ,Disease Susceptibility ,Mycobacterium tuberculosis - Abstract
Tuberculosis (TB), the world's deadliest bacterial infection, afflicts more human males than females, with a male/female (M/F) ratio of 1.7. Sex disparities in TB prevalence, pathophysiology, and clinical manifestations are widely reported, but the underlying biological mechanisms remain largely undefined. This review assesses epidemiological data on sex disparity in TB, as well as possible underlying hormonal and genetic mechanisms that might differentially modulate innate and adaptive immune responses in males and females, leading to sex differences in disease susceptibility. We consider whether this sex disparity can be extended to the efficacy of vaccines and discuss novel animal models which may offer mechanistic insights. A better understanding of the biological factors underpinning sex-related immune responses in TB may enable sex-specific personalized therapies for TB.
- Published
- 2022
45. Impact of Seasonal Coronavirus Antibodies on SARS-CoV-2 Vaccine Responses in Solid Organ Transplant Recipients
- Author
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Andrew H, Karaba, Weiqiang, Zhou, Shuai, Li, Tihitina Y, Aytenfisu, Trevor S, Johnston, Olivia, Akinde, Yolanda, Eby, Aura T, Abedon, Jennifer L, Alejo, Caroline X, Qin, Elizabeth A, Thompson, Jacqueline M, Garonzik-Wang, Joel N, Blankson, Andrea L, Cox, Justin R, Bailey, Sabra L, Klein, Andrew, Pekosz, Dorry L, Segev, Aaron A R, Tobian, and William A, Werbel
- Abstract
Antibody responses to SARS-CoV-2 vaccination are reduced in solid organ transplant recipients (SOTRs). We report that increased levels of pre-existing antibodies to seasonal coronaviruses are associated with decreased antibody response to SARS-CoV-2 vaccination in SOTRs, supporting that antigenic imprinting modulates vaccine responses in this immunosuppressed population.
- Published
- 2022
46. Sex biases in infectious diseases research
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Santosh Dhakal, Sabal Chaulagain, and Sabra L. Klein
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Male ,Sex Characteristics ,Sex Factors ,Bias ,Immunology ,Immunology and Allergy ,Humans ,Female ,Communicable Diseases - Abstract
Reporting the distribution and inclusion of both males and females in immunology and infectious diseases research is improving, but rigorous analyses of differential outcomes between males and females, including mechanistic inquiries into the causes of sex differences, still lags behind.
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- 2022
47. Sex disparities matter in cancer development and therapy
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Franco Caramia, Ygal Haupt, Sue Haupt, Sabra L. Klein, and Joshua B. Rubin
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Male ,Sexual identity ,business.industry ,Incidence ,Applied Mathematics ,General Mathematics ,Incidence (epidemiology) ,MEDLINE ,Cancer ,Translational research ,Precision medicine ,medicine.disease ,Affect (psychology) ,Article ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Neoplasms ,030220 oncology & carcinogenesis ,Genetic predisposition ,medicine ,Humans ,Female ,business ,Demography - Abstract
Curing cancer through precision medicine is the paramount aim of the new wave of molecular and genomic therapies. Currently, whether patients with non-reproductive cancers are male or female according to their sex chromosomes is not adequately considered in patient standard of care. This is a matter of consequence because there is growing evidence that these cancer types generally initiate earlier and are associated with higher overall incidence and rates of death in males compared with females. Gender, in contrast to sex, refers to a chosen sexual identity. Hazardous lifestyle choices (notably tobacco smoking) differ in prevalence between genders, aligned with disproportionate cancer risk. These add to underlying genetic predisposition and influences of sex steroid hormones. Together, these factors affect metabolism, immunity and inflammation, and ultimately the fidelity of the genetic code. To accurately understand how human defences against cancer erode, it is crucial to establish the influence of sex. Our Perspective highlights evidence from basic and translational research indicating that including genetic sex considerations in treatments for patients with cancer will improve outcomes. It is now time to adopt the challenge of overhauling cancer medicine based on optimized treatment strategies for females and males.
- Published
- 2021
48. Sex- and Gender-Based Pharmacological Response to Drugs
- Author
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Ilaria Campesi, Mark L. Heiman, Heiner K. Berthold, Vera Regitz-Zagrosek, Anne Z. Murphy, Santosh Dakal, Ioanna Gouni-Berthold, Franck Mauvais-Jarvis, Karen Reue, Flavia Franconi, Juan Jesus Carrero, Joshua B. Rubin, Sabra L. Klein, and Alexandra Kautzky-Willer
- Subjects
Male ,0301 basic medicine ,Pharmacology ,Sex Characteristics ,business.industry ,MEDLINE ,Bioinformatics ,Precision medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Pharmaceutical Preparations ,Pharmacokinetics ,Humans ,Molecular Medicine ,Medicine ,Female ,Epigenetics ,Precision Medicine ,business ,030217 neurology & neurosurgery ,Organ system - Abstract
In humans, the combination of all sex-specific genetic, epigenetic, and hormonal influences of biologic sex produces different in vivo environments for male and female cells. We dissect how these influences of sex modify the pharmacokinetics and pharmacodynamics of multiple drugs and provide examples for common drugs acting on specific organ systems. We also discuss how gender of physicians and patients may influence the therapeutic response to drugs. We aim to highlight sex as a genetic modifier of the pharmacological response to drugs, which should be considered as a necessary step toward precision medicine that will benefit men and women. SIGNIFICANCE STATEMENT: This study discusses the influences of biologic sex on the pharmacokinetics and pharmacodynamics of drugs and provides examples for common drugs acting on specific organ systems. This study also discusses how gender of physicians and patients influence the therapeutic response to drugs.
- Published
- 2021
49. Short Communication: Genetic Variation in Human IL10 Proximal Promoter and Susceptibility to HIV-1 Infection in Mali, West Africa
- Author
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Souleymane Diallo, Sounkalo Dao, D Goita, Michael E. Urbanowski, Chad J. Achenbach, Bocar Baya, Yeya dit Sadio Sarro, Mamadou Dembele, Robert L. Murphy, Michael Belson, Djeneba Dabitao, Bourahima Kone, Jane L. Holl, Seydou Doumbia, William R. Bishai, Mahamadou Diakite, Jay H. Bream, Nadie Coulibaly, Mamadou Wague, and Sabra L. Klein
- Subjects
Genetics ,Proximal promoter ,Host (biology) ,Immunology ,Haplotype ,Human immunodeficiency virus (HIV) ,Single-nucleotide polymorphism ,Biology ,medicine.disease_cause ,West africa ,Interleukin 10 ,Infectious Diseases ,Virology ,Genetic variation ,medicine - Abstract
It is now recognized that to fully understand the role of host genetic variation on susceptibility to HIV-1 infection, investigations must be extended to African populations. We sought to determine...
- Published
- 2021
50. Mission, Organization, and Future Direction of the Serological Sciences Network for COVID-19 (SeroNet) Epidemiologic Cohort Studies
- Author
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Jane C Figueiredo, Fred R Hirsch, Lawrence H Kushi, Wendy N Nembhard, James M Crawford, Nicholas Mantis, Laurel Finster, Noah M Merin, Akil Merchant, Karen L Reckamp, Gil Y Melmed, Jonathan Braun, Dermot McGovern, Samir Parekh, Douglas A Corley, Namvar Zohoori, Benjamin C Amick, Ruofei Du, Peter K Gregersen, Betty Diamond, Emanuela Taioli, Carlos Sariol, Ana Espino, Daniela Weiskopf, Alba Gifoni, James Brien, William Hanege, Marc Lipsitch, David A Zidar, Ann Scheck McAlearney, Ania Wajnberg, Joshua LaBaer, E Yvonne Lewis, Raquel A Binder, Ann M Moormann, Catherine Forconi, Sarah Forrester, Jennifer Batista, John Schieffelin, Dongjoo Kim, Giulia Biancon, Jennifer VanOudenhove, Stephanie Halene, Rong Fan, Dan H Barouch, Galit Alter, Swetha Pinninti, Suresh B Boppana, Sunil K Pati, Misty Latting, Andrew H Karaba, John Roback, Rafick Sekaly, Andrew Neish, Ahnalee M Brincks, Douglas A Granger, Amy B Karger, Bharat Thyagarajan, Stefani N Thomas, Sabra L Klein, Andrea L Cox, Todd Lucas, Debra Furr-Holden, Kent Key, Nicole Jones, Jens Wrammerr, Mehul Suthar, Serre Yu Wong, Natalie M Bowman, Viviana Simon, Lynne D Richardson, Russell McBride, Florian Krammer, Meenakshi Rana, Joshua Kennedy, Karl Boehme, Craig Forrest, Steve W Granger, Christopher D Heaney, Maria Knight Lapinski, Shannon Wallet, Ralph S Baric, Luca Schifanella, Marcos Lopez, Soledad Fernández, Eben Kenah, Ashish R Panchal, William J Britt, Iñaki Sanz, Madhav Dhodapkar, Rafi Ahmed, Luther A Bartelt, Alena J Markmann, Jessica T Lin, Robert S Hagan, Matthew C Wolfgang, and Jacek Skarbinski
- Subjects
Pediatric ,SARS-CoV-2 ,Prevention ,COVID-19 ,cohort ,Pneumonia ,SeroNet ,Vaccine Related ,serosurveillance ,Emerging Infectious Diseases ,Infectious Diseases ,Oncology ,Clinical Research ,Biodefense ,Pneumonia & Influenza ,epidemiology ,Aetiology ,Digestive Diseases ,Lung ,Cancer ,2.4 Surveillance and distribution - Abstract
Background Global efforts are needed to elucidate the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the underlying cause of coronavirus disease 2019 (COVID-19), including seroprevalence, risk factors, and long-term sequelae, as well as immune responses after vaccination across populations and the social dimensions of prevention and treatment strategies. Methods In the United States, the National Cancer Institute in partnership with the National Institute of Allergy and Infectious Diseases, established the SARS-CoV-2 Serological Sciences Network (SeroNet) as the nation’s largest coordinated effort to study coronavirus disease 2019. The network comprises multidisciplinary researchers bridging gaps and fostering collaborations among immunologists, epidemiologists, virologists, clinicians and clinical laboratories, social and behavioral scientists, policymakers, data scientists, and community members. In total, 49 institutions form the SeroNet consortium to study individuals with cancer, autoimmune disease, inflammatory bowel diseases, cardiovascular diseases, human immunodeficiency virus, transplant recipients, as well as otherwise healthy pregnant women, children, college students, and high-risk occupational workers (including healthcare workers and first responders). Results Several studies focus on underrepresented populations, including ethnic minorities and rural communities. To support integrative data analyses across SeroNet studies, efforts are underway to define common data elements for standardized serology measurements, cellular and molecular assays, self-reported data, treatment, and clinical outcomes. Conclusions In this paper, we discuss the overarching framework for SeroNet epidemiology studies, critical research questions under investigation, and data accessibility for the worldwide scientific community. Lessons learned will help inform preparedness and responsiveness to future emerging diseases.
- Published
- 2022
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