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Background: Identifying genetic factors that influence poxvirus immunity across races may assist in the development of better vaccines and approaches for vaccine development.Methods: We performed an extensive candidate-gene genetic screen (across 32 cytokine and cytokine receptor genes) in a racially diverse cohort of 1056 healthy adults after a single dose of smallpox vaccine. Associations between single-nucleotide polymorphisms (SNPs)/haplotypes and vaccinia virus-specific neutralizing antibodies were assessed using linear regression methodologies.Results: The combined analysis identified 63 associations between candidate SNPs and antibody levels after smallpox vaccination with P < .05. Thirty-one of these were within the IL18R1 and IL18 genes. Five IL18R1 SNPs, including a coding synonymous polymorphism rs1035130 (Phe251Phe) and 2 promoter SNPs (rs6710885, rs2287037), all in linkage disequilibrium, were associated with significant variations in antibody levels in both Caucasians (P ≤ .016) and African Americans (P ≤ .025). Similarly, associations with 2 intronic IL18 SNPs (rs2043055 and rs5744280) were consistent in the Caucasian (P ≤ .023) and African American samples (P ≤ .014). Haplotype analysis revealed highly significant associations between IL18R1 haplotypes and vaccinia virus-specific antibody levels (P < .001, by combined analysis) that were consistent across races.Conclusions: Our study provides evidence for IL18 and IL18R1 genes as plausible genes regulating the humoral immune response to smallpox vaccine in both Caucasians and African Americans. [ABSTRACT FROM AUTHOR]

Context: In 1999, the US Congress directed the Centers for Disease Control and Prevention to conduct a pivotal safety and efficacy study of anthrax vaccine adsorbed (AVA).Objective: To determine the effects on serological responses and injection site adverse events (AEs) resulting from changing the route of administration of AVA from subcutaneous (s.q.) to intramuscular (i.m.) and omitting the week 2 dose from the licensed schedule.Design, Setting, and Participants: Assessment of the first 1005 enrollees in a multisite, randomized, double-blind, noninferiority, phase 4 human clinical trial (ongoing from May 2002).Intervention: Healthy adults received AVA by the s.q. (reference group) or i.m. route at 0, 2, and 4 weeks and 6 months (4-SQ or 4-IM; n = 165-170 per group) or at a reduced 3-dose schedule (3-IM; n = 501). A control group (n = 169) received saline injections at the same time intervals.Main Outcome Measures: Noninferiority at week 8 and month 7 of anti-protective antigen IgG geometric mean concentration (GMC), geometric mean titer (GMT), and proportion of responders with a 4-fold rise in titer (%4 x R). Reactogenicity outcomes were proportions of injection site and systemic AEs.Results: At week 8, the 4-IM group (GMC, 90.8 microg/mL; GMT, 1114.8; %4 x R, 97.7) was noninferior to the 4-SQ group (GMC, 105.1 microg/mL; GMT, 1315.4; %4 x R, 98.8) for all 3 primary end points. The 3-IM group was noninferior for only the %4 x R (GMC, 52.2 microg/mL; GMT, 650.6; %4 x R, 94.4). At month 7, all groups were noninferior to the licensed regimen for all end points. Solicited injection site AEs assessed during examinations occurred at lower proportions in the 4-IM group compared with 4-SQ. The odds ratio for ordinal end point pain reported immediately after injection was reduced by 50% for the 4-IM vs 4-SQ groups (P < .001). Route of administration did not significantly influence the occurrence of systemic AEs.Conclusions: The 4-IM and 3-IM regimens of AVA provided noninferior immunological priming by month 7 when compared with the 4-SQ licensed regimen. Intramuscular administration significantly reduced the occurrence of injection site AEs. Trial Registration clinicaltrials.gov Identifier: NCT00119067. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the immunogenicity, reactogenicity, and tolerability of a prototype human papillomavirus (HPV) 16 viruslike particle (VLP) vaccine directed against the L1 capsid protein. SUBJECTS AND METHODS: We enrolled healthy nonpregnant women aged 18 to 26 years into a 2-year, double-blind, dose-ranging multicenter trial (October 12, 1998, to September 30, 2001). Subjects were assigned to study groups to receive a 3-dose regimen (day 0, month 2, and month 6) of 1 of 4 vaccine doses: 10 microg, 20 microg, 40 microg, or 80 microg or placebo. Serum anti-HPV 16 L1 antibody (sL1Ab) geometric mean titers (GMTs) were measured at day 0, at month 3, at month 7, and every 6 months for a total of 2 years using a radioimmunoassay. The primary immunogenicity analyses evaluated GMTs at month 7 in L1Ab-seronegative subjects at baseline. Vaccine tolerability was also assessed. RESULTS: A total of 480 subjects were randomized to receive placebo (n=52) or 10 microg (n=112), 20 microg (n=105), 40 microg (n=104), or 80 microg (n=107) of HPV 16 L1 VLP vaccine. At baseline, 75% of subjects were L1Ab seronegative. All vaccine doses produced a statistically significant sL1Ab response vs placebo (P<.001). At the completion of the vaccination regimen, sL1Ab GMTs in baseline-seronegative subjects were 36- to 78-fold higher than the sL1Ab GMT at day 0 observed in subjects who had mounted an immune response to HPV 16 infection before enrollment. Serum L1Ab GMTs remained high throughout the 1.5-year postvaccination period. Postvaccination sL1Ab GMTs were 1.1- to 2.4-fold higher in women who had detectable sL1Ab levels at enrollment compared with those in baseline-seronegative subjects, particularly in the persistence phase. The vaccine was generally well tolerated with no statistically significant differences in injection site or systemic adverse experiences among treatment groups. CONCLUSION: Immunization with this novel HPV 16 L1 VLP vaccine was well tolerated and produced an immunogenic response that persisted for at least 1.5 years after the final dose. [ABSTRACT FROM AUTHOR]

The US measles epidemics of 1989-1991 included a series of outbreaks resulting from vaccine failure. A series of studies was launched aimed at elucidating the mechanisms of this vaccine failure. A meta-analysis of the literature examining epidemics in vaccinated populations was conducted, which showed that the secondary vaccine failure rate (development of the disease despite an initial or primary vaccine success) is no more than 0.2%. The overwhelming proportion of measles vaccine failure was due to primary vaccine failure (failure to ever generate antibody from antigenic stimulation). This comparison of two geographically distinct communities revealed that 10% of children previously vaccinated against measles lacked antibody on follow-up and that these vaccine failures clustered in families. A study of monozygotic and dizygotic twins revealed a high degree of heritability of measles vaccine antibody level. Subsequent studies found associations with both class I and class II alleles in these population-based studies. In the future, detection of the specific peptides that interact with human leukocyte antigen (HLA) molecules may serve as the basis for improved vaccines and address vaccine failure that results from cold-chain problems, immaturity of the immune system, malnutrition and maternal immunity. [ABSTRACT FROM AUTHOR]

Although influenza vaccine delivery strategies have improved coverage rates to unprecedented levels nationally among persons aged 65 years and older, influenza remains one of the greatest vaccine-preventable threats to public health among elderly in the US. A new, intranasal live attenuated influenza vaccine (LAIV) was recently approved by the US FDA for use in persons aged 5-49 years, which excludes the elderly population. Limitations of immune response to inactivated influenza vaccine (IAIV) and effectiveness of current influenza vaccination strategies among the elderly suggest that a combined approach using LAIV and/or the IAIV in various permutations might benefit this group. We explore characteristics of the LAIV, data regarding its utility in protecting against influenza in the elderly, and challenges and opportunities regarding potential combined inactivated/live attenuated vaccination strategies for the elderly. Although LAIV appears to hold promise either alone or in combination with IAIV, large well conducted randomised trials are necessary to define further the role of LAIV in preventing influenza morbidity and mortality among the elderly. We also suggest that innovative vaccine coverage strategies designed to optimise prevention and control of influenza and minimise viral transmission in the community must accompany, in parallel, the acquisition of clinical trials data to best combat morbidity and mortality from influenza. [ABSTRACT FROM AUTHOR]

New vaccines have been licensed for hepatitis A, varicella, and typhoid. This paper reviews these vaccines and their recommended uses in adults. Special attention is given to a new national policy establishing age 50 years as a time for review of preventive health measures with emphasis on evaluating risk factors that indicate a need for pneumococcal vaccine and the initiation of annual influenza immunization. [ABSTRACT FROM AUTHOR]

The authors make the case for mandatory vaccination. Also: Edie Brous looks at the legal aspects, and Douglas P. Olsen examines the ethics, online only:http://links.lww.com/A361. [ABSTRACT FROM AUTHOR]

Concern about side effects constitutes a major deterrent to patient compliance with influenza vaccination, yet there is a paucity of data about the occurrence of adverse reactions in the population targeted for immunization. We conducted a randomized, double-blind, crossover trial to compare the frequency of adverse reactions following administration of 1988-1989 trivalent split-antigen influenza vaccine and saline placebo. Outpatient veterans 65 years of age or over (n = 336) were recruited by mail and were randomly assigned to receive vaccine followed 2 weeks later by placebo injection or placebo followed 2 weeks later by vaccine. There was no significant difference between influenza vaccine and placebo with respect ot the proportion of subjects reporting disability or systemic symptoms. [ABSTRACT FROM AUTHOR]

Influenza is an important contributor to population and individual morbidity and mortality. The current influenza pandemic with novel H1N1 has highlighted the need for health care professionals to better understand the processes involved in creating influenza vaccines, both for pandemic as well as for seasonal influenza. This review presents an overview of influenza-related topics to help meet this need and includes a discussion of the burden of disease, virology, epidemiology, viral surveillance, and vaccine strain selection. We then present an overview of influenza vaccine-related topics, including vaccine production, vaccine efficacy and effectiveness, influenza vaccine misperceptions, and populations that are recommended to receive vaccination. English-language articles in PubMed published between January 1, 1970, and October 7, 2009, were searched using key words human influenza, influenza vaccines, influenza A, and influenza B. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the variability of parental interest in the depth of detail provided regarding vaccine information. PARTICIPANTS AND METHODS: We performed a cross-sectional, observational study in a primary care pediatric practice from September 1 to September 30, 1995. We provided each participant an opportunity to use a self-directed, computer-based information system using the varicella vaccine as a prototype. The system covered 7 topics regarding the vaccine and offered 5 stages of information, ranging from general, indisputable information at stage 1 to less common, potentially unresolved details at stage 5. Parents viewed stage 1 information for each topic. Parents would then choose to either view more stages or view the next topic. RESULTS: Of 130 parents visiting the pediatric practice, 112 (86%) agreed to participate. We found substantial variability in the amount of information sought. Some parents stopped with stage 1 information (15%-45%, depending on the topic), whereas others indicated they would seek more information beyond the fifth stage (2%-14%). Overall, parents reported high satisfaction with the system. CONCLUSION: Quantifiable variability exists in parents' requirements for vaccine information, and our information system addresses this issue. [ABSTRACT FROM AUTHOR]

Within 2 months of its discovery last spring, a novel influenza A (H1N1) virus, currently referred to as 2009 H1N1, caused the first influenza pandemic in decades. The virus has caused disproportionate disease among young people with early reports of virulence similar to that of seasonal influenza. This clinical review provides an update encompassing the virology, epidemiology, clinical manifestations, diagnosis, treatment, and prevention of the 2009 H1N1 virus. Because information about this virus, its prevention, and treatment are rapidly evolving, readers are advised to seek additional information. We performed a literature search of PubMed using the following keywords: H1N1, influenza, vaccine, pregnancy, children, treatment, epidemiology, and review. Studies were selected for inclusion in this review on the basis of their relevance. Recent studies and articles were preferred. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To determine the seroprevalence of varicella antibody among recent Somali refugees living in Olmsted County, Minnesota, and to estimate the risk of varicella-zoster virus (VZV) infection in this group. SUBJECTS AND METHODS: We obtained blood samples from the study subjects, along with demographic information, immunization records, and vaccine-preventable disease history. Serum samples were tested using a whole-virus IgG VZV-specific commercial enzyme-linked immunosorbent assay kit. This study was completed in 1998. RESULTS: Overall, 200 Somali refugees, comprising 33 extended families, were interviewed, with 193 providing adequate blood samples. Thirty-five subjects (18%) were seronegative for varicelia. Males had a significantly higher seronegativity rate (25% [n = 23]) compared with females (12% [n = 12]; P = .02); however, this association disappeared after adjustment for age and varicella infection history. Five percent (5/92) of adults were seronegative compared with 30% (30/101) of all children (P < .001). Eight percent (5/61) of the adult females were seronegative, whereas none (0/31) of the adult males were seronegative. Conversely, 38% (23/60) of male children were seronegative compared with 17% (7/41) of female children (P < .001). CONCLUSION: These results demonstrate a high prevalence of varicella seronegativity among Somali refugees who have immigrated to an endemic area. We recommend instituting improved education regarding varicella among Somali communities and increasing vaccine uptake or routine testing for serum varicella antibody to prevent VZV-related morbidity and mortality, particularly in adolescents, adult refugees, and women of childbearing age. [ABSTRACT FROM AUTHOR]

Older age (≥ 65 years) is associated with impaired responses to influenza vaccination, leading to the preferential recommendation of MF59-adjuvanted (MF59Flu) or high-dose (HDFlu) influenza vaccines for this age group in the United States. Herein, we characterized transcriptomic profiles of CD4 + T cells isolated from 234 recipients (≥ 65 years) of either MF59Flu or HDFlu vaccine, prior to vaccination and 28 days thereafter. We identified 412 and 645 differentially expressed genes (DEGs) in CD4 + T cells of older adults after receiving MF59Flu and HDFlu, respectively. DEGs in CD4 + T cells of MF59Flu recipients were enriched in 14 KEGG pathways, all of which were downregulated. DEGs in CD4 + T cells of HDFlu recipients were enriched in 11 upregulated pathways and 20 downregulated pathways. CD4 + T cells in both vaccine groups shared 50 upregulated genes and 75 downregulated genes, all of which were enriched in 7 KEGG pathways. The remaining 287 and 520 DEGs were specifically associated with MF59Flu and HDFlu, respectively. Unexpectedly, none of these DEGs was significantly correlated with influenza A/H3N2-specific HAI titers, suggesting these DEGs at the individual level may have a limited role in protection against influenza. Our findings emphasize the need for further investigation into other factors influencing immunity against influenza in older adults., (© 2024. The Author(s).)

Objectives: This study aims to identify COVID-19 breakthrough infections among people with HIV (PWH) across different phases of the pandemic and explore whether differential immune dysfunctions are associated with breakthrough infections., Design and Methods: This retrospective population-based cohort study used data from an integrated electronic health record (EHR) database in South Carolina (SC). Breakthrough infection was defined as the first COVID-19 diagnosis documented in the state agency after the date an individual was fully vaccinated (ie, 2 doses of Pfizer/BNT162b2 or Moderna/mRNA-1273, or 1 dose of Janssen/Ad26.COV2.S) through June 14, 2022. We analyzed the risk and associated factors of the outcome using Cox proportional hazards models., Results: Among 7596 fully vaccinated PWH, the overall rate of breakthrough infections was 118.95 cases per 1000 person-years. When compared with the alpha-dominant period, the breakthrough infection rate was higher during both delta-dominant (HR: 1.50; 95% CI: 1.25 to 1.81) and omicron-dominant (HR: 2.86; 95% CI: 1.73 to 4.73) periods. Individuals who received a booster dose had a lower likelihood of breakthrough infections (HR: 0.19; 95% CI: 0.15 to 0.24). There was no association of breakthrough infections with degree of HIV viral suppression, but a higher CD4 count was significantly associated with fewer breakthroughs among PWH (>500 vs <200 cells/mm3: HR: 0.68; 95% CI: 0.49 to 0.94)., Conclusions: In our PWH population, the incidence of breakthrough infections was high (during both delta-dominant and omicron-dominant periods) and mainly associated with the absence of a booster dose in patients older than 50 years, with comorbidities and low CD4 count., Competing Interests: Dr. G.A.P. is the chair of a Safety Evaluation Committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. Dr. G.A.P. provides consultative advice to AiZtech; Emergent Biosolutions; GlaxoSmithKline; Invivyd; Janssen Global Services, LLC; Merck & Co. Inc.; Moderna; Novavax; and Syneos Health. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies. Dr. G.A.P. holds patents related to vaccinia, influenza, and measles peptide vaccines. Dr. G.A.P. has received grant funding from ICW Ventures for preclinical studies on a peptide-based COVID-19 vaccine. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policies. Dr. G.A.P. is an adviser to the White House and World Health Organization on COVID-19 vaccines and monkeypox, respectively., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Although neutralizing antibody is an established correlate of protection for measles, T cell-mediated responses play at least two critical roles in immunity to measles: first, through provision of 'help' enabling robust humoral immune responses; and second, through clearance of measles virus-infected cells. Previously, we identified 13 measles-derived peptides that bound to human leukocyte antigen (HLA) molecules in Priess cells infected with measles virus. In this study, we evaluated the immunogenicity of these peptides in a transgenic mouse model. Our results demonstrated that these peptides induced Th1-biased immune responses at varying levels. Of the 13 peptides, the top four immunogenic peptides were further selected for a viral challenge study in mice. A vaccine based on a combination of these four peptides reduced morbidity and weight loss after viral challenge compared to placebo. Our results emphasize the potential of T cell-mediated, peptide-based vaccines against measles., (© 2024. The Author(s).)

For many rare disease (RD) patients, allogenic transplantation represents an effective therapy, improving overall survival rates and quality of life (QoL). Globally, ∼1% of liver transplants are performed for RDs and rare indications. However, patients and carers report unmet needs on their pathway toward treatment-in education and therapeutic measures, oftentimes shouldering expertise-building responsibility themselves. These issues are exacerbated in child patients. Estimates indicate that 6% to 8% of Poland's population (2.3-3 million persons) are burdened by RDs and potentially face such issues. This work aims to identify shortcomings of Polish policy in the field of educational and therapeutic measures for RD transplant candidates and recipients. Based on solutions introduced by pioneers, recommendations are formulated regarding priority actions. An analysis of national, transnational, and individual-center programs, directed at patients during their path from diagnosis to life post-transplant, was conducted. The investigation uncovered measure gaps not addressed by the National Plan for Rare Diseases-in fields of patient and stakeholder education (pre- and post-transplant), psychological care provision, specialized center creation, integration of data scattered among registries with the national insurer's database, and artificial intelligence (AI) tool implementation to support both early diagnostic efforts and tailoring of patient treatment. Programs directed at RD transplant candidates and recipients must aim to ensure that a satisfactory psychosomatic condition of the patient is maintained before and following the procedure, therefore lending credence to success. This necessitates early diagnosis schemes, and personalized medicine, multidisciplinary approaches to the individual, achievable only through big data system creation and AI introduction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Warsaw Medical University, Dept. of General and Transplantation Surgery , Warsaw PL. Published by Elsevier Inc. All rights reserved.)

B cell transcriptomic signatures hold promise for the early prediction of vaccine-induced humoral immunity and vaccine protective efficacy. We performed a longitudinal study in 232 healthy adult participants before/after a 3 rd dose of MMR (MMR3) vaccine. We assessed baseline and early transcriptional patterns in purified B cells and their association with measles-specific humoral immunity after MMR vaccination using two analytical methods ("per gene" linear models and joint analysis). Our study identified distinct early transcriptional signatures/genes following MMR3 that were associated with measles-specific neutralizing antibody titer and/or binding antibody titer. The most significant genes included: the interleukin 20 receptor subunit beta/ IL20RB gene (a subunit receptor for IL-24, a cytokine involved in the germinal center B cell maturation/response); the phorbol-12-myristate-13-acetate-induced protein 1/ PMAIP1 , the brain expressed X-linked 2/ BEX2 gene and the B cell Fas apoptotic inhibitory molecule/ FAIM , involved in the selection of high-affinity B cell clones and apoptosis/regulation of apoptosis; as well as IL16 (encoding the B lymphocyte-derived IL-16 ligand of CD4), involved in the crosstalk between B cells, dendritic cells and helper T cells. Significantly enriched pathways included B cell signaling, apoptosis/regulation of apoptosis, metabolic pathways, cell cycle-related pathways, and pathways associated with viral infections, among others. In conclusion, our study identified genes/pathways linked to antigen-induced B cell proliferation, differentiation, apoptosis, and clonal selection, that are associated with, and impact measles virus-specific humoral immunity after MMR vaccination., Competing Interests: Dr. GP offers consultative advice to Johnson & Johnson/Janssen Global Services LLC, and is the chair of a Safety Evaluation Committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. Dr. GP also offers consultative advice on vaccine development to Merck & Co., Medicago, GlaxoSmithKline, Sanofi Pasteur, Emergent Biosolutions, Dynavax, Genentech, Eli Lilly and Company, Kentucky Bioprocessing Inc, Bavarian Nordic, AstraZeneca, Exelixis, Regeneron, Janssen, Vyriad, Moderna, and Genevant Sciences, Inc. Drs. GP and IO hold patents related to vaccinia and measles peptide vaccines. Drs. RK, GP, and IO hold a patent related to vaccinia peptide vaccines. Drs. GP, RK, IO and IH hold a patent related to the impact of single nucleotide polymorphisms on measles vaccine immunity. Drs. GP, RK, and IO have received grant funding from ICW Ventures for preclinical studies on a peptide-based COVID-19 vaccine. Dr. RK has received funding from Merck Research Laboratories to study waning immunity to mumps vaccine. Dr. RK also offers consultative advice on vaccine development to Merck & Co. and Sanofi Pasteur. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Haralambieva, Chen, Quach, Ratishvili, Warner, Ovsyannikova, Poland and Kennedy.)

Vaccination is one of the most important public health tools in the prevention of infectious diseases, and in preserving life and health. While vaccines are generally safe and usually produce only transient side effects, other types of vaccine-associated adverse events do occur. Some of these reactions are immediate and easily observable or measurable, such as swelling at the injection site or a transient fever. Others however are not immediately obvious, or are even clinically "silent" or cryptic, making them challenging to identify and link directly to a vaccine. It is critical to be vigilant about rare, silent, or subtle reactions. Public health agencies and healthcare providers can play a much more favorable and vital role in establishing vaccine trust by enlarging the current vaccine safety paradigm, and in publishing and communicating, in full, these risks and benefits transparently to the public. While there are challenges in collecting and studying cryptic adverse events characterized by subjective symptoms without biomarkers, rigorous pharmacovigilance, continued research, and high-quality study designs can assist in better understanding and addressing these concerns - and in building public trust about vaccines and vaccine safety surveillance completeness., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Steven Black is a consultant for GSK on program planning and also to CEPI regarding vaccine safety. Dr. Greg Poland Dr. Poland is the chair of a Safety Evaluation Committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. Dr. Poland provides consultative advice to AiZtech; Atria; GlaxoSmithKline; Invivyd; Janssen Global Services, LLC; Merck & Co. Inc.; Moderna; Novavax; Pfizer, Syneos Health; and Valneva. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies. Dr. Poland holds patents related to vaccinia, influenza, and measles peptide vaccines. Dr. Poland has received grant funding from ICW Ventures for preclinical studies on a peptide-based COVID-19 vaccine. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policies. Dr. Poland is an adviser to the White House and World Health Organization on COVID-19 vaccines and monkeypox, respectively., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: C Raina MacIntyre currently receives funding from Sanofi for research on seasonal influenza and pertussis; and is on the WHO COVID-19 Vaccine Composition Technical Advisory Group. Dr. Poland is the chair of a Safety Evaluation Committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. Dr. Poland provides consultative advice to 3D Communications; AiZtech; AstraZeneca; Dynavax; Emergent; Exelixis; GlaxoSmithKline; Invivyd; Johns Hopkins; Johnson & Johnson/Janssen; Laura Lee Hall; Medicago; Medscape/WebMD; Merck & Co. Inc.; Moderna; NovaSource/NorthStar Energy; Novavax; Ocugen; Regeneron; Sanofi; Syneos Health; and Valneva. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies. Dr. Poland holds patents related to vaccinia, influenza, and measles peptide vaccines. Dr. Poland has received grant funding from ICW Ventures for preclinical studies on a peptide-based COVID-19 vaccine. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policies. Dr. Poland is an adviser to the White House and World Health Organization on COVID-19 vaccines and monkeypox, respectively.

The responsiveness/cross-binding of vaccine-induced memory B cells/MBCs to previous and emerging divergent SARS-CoV-2 variants (e.g., Omicron) is understudied. In this longitudinal study subjects receiving two or three doses of monovalent ancestral strain-containing COVID-19 mRNA vaccine were evaluated. In contrast to others, we observed significantly lower frequencies of MBCs reactive to the receptor-binding domain/RBD, the N-terminal domain/NTD, and the S1 of Omicron/BA.1, compared to Wuhan and Delta, even after a 3rd vaccine dose/booster. Our study is a proof of concept that MBC cross-reactivity to variants with greater sequence divergence from the vaccine strain may be overestimated and suggests that these variants may exhibit immune escape with reduced recognition by circulating pre-existing MBCs upon infection., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rick Kennedy reports financial support was provided by Mayo Clinic for SARS-CoV-2 research. Gregory Poland reports financial support was provided by National Institutes of Health (R01 AI48793: Poland PI). Dr. Poland is the chair of a Safety Evaluation Committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. Dr. Poland provides consultative advice to AiZtech; Atria; GlaxoSmithKline; Invivyd; Janssen Global Services, LLC; Merck & Co. Inc.; Moderna; Novavax; and Syneos Health. Drs. Poland and Ovsyannikova hold patents related to vaccinia and measles peptide vaccines. Drs. Kennedy, Poland, and Ovsyannikova hold a patent related to vaccinia peptide vaccines. Drs. Poland, Kennedy, and Ovsyannikova have received grant funding and royalties from ICW Ventures for pre-clinical studies on a peptide-based COVID-19 vaccine. Drs. Poland, Kennedy, Ovsyannikova and Haralambieva hold a patent related to the impact of single nucleotide polymorphisms on measles vaccine immunity. Dr. Kennedy has received funding from Merck Research Laboratories to study waning immunity to mumps vaccine. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policy. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: This study aims to characterize and compare COVID-19 breakthrough infections between people living with and without HIV across different phases of the pandemic., Methods: Using statewide HIV cohort data, the study population included adult residents in South Carolina (SC) (>18 years old) who were fully vaccinated between January 02, 2021 and April 14, 2022 when Alpha, Delta, and Omicron variants were circulating in SC. We used the Cox proportional hazard model to investigate the association between HIV infection and breakthrough infection, adjusting for relevant covariates., Results: Among 2,144,415 vaccinated individuals, 8,335 were people living with HIV (PLWH) and 2,136,080 were people without HIV (PWoH). After propensity score matching, HIV infection was not significantly associated with breakthrough infection rate. However, when comparing breakthrough infections among individuals without any booster dose, PLWH had a higher risk of breakthrough infections (adjusted Hazard Ration: 1.19; 95% confidence interval: 1.03-1.39). Compared to PWoH, PLWH with high levels of clusters of differentiation 4 (CD4) count or viral suppression were not associated with breakthrough infections., Conclusions: Our findings do not support a broad conclusion that COVID-19 vaccine effectiveness is lower among PLWH, while we did find that PLWH had a higher risk of breakthrough infection compared to PWoH if they did not receive a booster dose., Competing Interests: Declaration of competing interest Dr. Poland is the chair of a Safety Evaluation Committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. Dr. Poland provides consultative advice to AiZtech; Atria; GlaxoSmithKline; Invivyd; Janssen Global Services, LLC; Merck & Co. Inc.; Moderna; Novavax; and Syneos Health. Dr. Poland holds patents related to vaccinia, influenza, and measles peptide vaccines. Dr. Poland has received grant funding from ICW Ventures for preclinical studies on a peptide-based COVID-19 vaccine. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policies. Dr. Poland is an adviser to the White House and World Health Organization on COVID-19 vaccines and monkeypox, respectively., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

SARS-CoV-2 remains a major global public health concern. Antibody waning and immune escape variant emergence necessitate the development of next generation vaccines that induce cross-reactive durable immune responses. T cell responses to SARS-CoV-2 demonstrate higher conservation, antigenic breadth, and longevity than antibody responses. Therefore, we sought to identify pathogen-derived T cell epitopes for a potential peptide-based vaccine. We pursued an approach leveraging: 1) liquid chromatography and tandem mass spectrometry (LC-MS/MS)-based identification of peptides from ancestral SARS-CoV-2-infected cell lines, 2) epitope prediction algorithms, and 3) overlapping peptide libraries. From this strategy, we identified 380 unique SARS-CoV-2-derived peptide sequences, including 53 antigenic HLA class I and class II peptides from multiple structural and non-structural/accessory viral proteins. These peptide sequences were highly conserved across variants of concern/interest (VoC/VoIs), and are estimated to achieve coverage of >96% of the world population. Our findings validate this discovery pipeline for peptide identification and immunogenicity testing, and are a crucial step toward the development of a next-generation multi-epitope SARS-CoV-2 peptide vaccine, and a novel vaccine platform methodology., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Dr. Poland is the chair of a Safety Evaluation Committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. Dr. Poland provides consultative advice to AiZtech; Atria; GlaxoSmithKline; Invivyd; Janssen Global Services, LLC; Merck & Co. Inc.; Moderna; Novavax; and Syneos Health. Dr. Poland is an adviser to the White House and World Health Organization on COVID-19 vaccines and monkeypox, respectively. Drs. Poland and Ovsyannikova hold patents related to vaccinia and measles peptide vaccines. Drs. Kennedy, Poland, and Ovsyannikova hold a patent related to vaccinia peptide vaccines. Drs. Poland, Kennedy, and Ovsyannikova have received grant funding and royalties from ICW Ventures for pre-clinical studies on a peptide-based COVID-19 vaccine. Drs. Poland, Kennedy, Ovsyannikova and Haralambieva hold a patent related to the impact of single nucleotide polymorphisms on measles vaccine immunity. Dr. Kennedy has received funding from Merck Research Laboratories to study waning immunity to mumps vaccine. Dr. Kennedy also offers consultative advice on vaccine development to Merck & Co. and Sanofi Pasteur. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policy.]., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The reduced effectiveness of standard-dose influenza vaccines in persons ≥65 years of age led to the preferential recommendation to use high-dose (HDFlu) or MF59-adjuvanted (MF59Flu) vaccines for this age group. Sleep is an important modulator of immune responses to vaccines and poor sleep health is common in older adults. However, potential effects of poor sleep health on immune responses to influenza vaccination in older adults remain largely unknown., Methods: We conducted a cohort study of 210 healthy participants age ≥65 years, who received either seasonal high-dose (HDFlu) or MF59-adjuvanted (MF59Flu) influenza vaccine. We assessed sleep characteristics in this cohort by standardized questionnaires and measured the antibody titer against influenza A/H3N2 virus in serum of study participants by hemagglutination inhibition assay on the day of immunization and 28 days thereafter. We then assessed the association between sleep characteristics and antibody titers., Results: Our results demonstrated that male, but not female, study participants with excessive daytime sleepiness had an impaired influenza A/H3N2-specific antibody response at Day 28 post-vaccination. No other associations were found between antibody titer and other sleep characteristics, including sleep quality and obstructive sleep apnea., Conclusion: Our results provide an additional and easily measured variable explaining poor vaccine effectiveness in older adults. Our results support that gaining sufficient sleep is a simple non-vaccine interventional approach to improve influenza immune responses in older adults. Our findings extend the literature on the negative influence of excessive daytime sleepiness on immune responses to influenza vaccination in older male adults., Competing Interests: Author GP is the chair of a Safety Evaluation Committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. Author GP also provides consultative advice on vaccine development to Merck & Co Keniworth, NJ., Medicago Quebec City, Quebec, GlaxoSmithKline Brentford, United Kingdom, Sanofi Pasteur Lyon, France, Emergent Biosolutions Gaithersburg, MD, AstraZeneca Cambridge, United Kingdom, Janssen Beerse, Belgium, and Moderna Cambridge, MA. Authors GP and IO hold patents related to vaccinia and measles peptide vaccines. Authors RK, GP, and IO hold a patent related to vaccinia peptide vaccines. Authors GP, RK, and IO have received grant funding and royalties from ICW Ventures for pre-clinical studies on a peptide-based COVID-19 vaccine. Author RK has received funding from Merck Research Laboratories to study waning immunity to mumps vaccine. Author VS serves as a consultant for Bayer, Lilly, Jazz Pharmaceuticals, Zoll, Huxley Medical, Wesper and ApniMed and is on the Scientific Advisory Board of Sleep Number. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policy. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Quach, Warner, Ovsyannikova, Covassin, Poland, Somers and Kennedy.)

The measles-mumps-rubella (MMR) vaccine has been widely used in the US, but measles and mumps outbreaks remain a public health issue in the US and elsewhere, even among individuals immunized with 2 doses of the vaccine. Immune correlates of vaccine-elicited protection against disease are typically assessed with serum antibody assays, but in some cases, these correlates fail to predict immunity, with the complexity and heterogeneity of the immune response. We used multicolor flow cytometry to evaluate changes in the frequency of peripheral T and B cell subsets in 82 study participants after receipt of a third dose of the M- M -R II vaccine (Merck & Co, Inc). We assessed correlations between flow cytometry variables and measles virus (MV), mumps virus (MuV), or rubella virus (RV)-specific immune response outcomes. Following a third vaccine dose, major changes were observed in the T-cell compartment. CD4 + T cell subsets were significantly increased from baseline to day 28, whereas CD8 + T cell subsets were predominantly decreased. Changes in regulatory T cells (Tregs) correlated with RV- and MV-specific immune outcomes and with high- and low-RV antibody responder groups, implicating the importance of Tregs in regulating MMR vaccine-induced immune responses. This information may help define additional correlates of protection and aid in the design of improved vaccines., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Poland is the chair of a Safety Evaluation Committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. Dr. Poland provides consultative advice on vaccine development to AiZtech, AstraZeneca UK Limited, Eli Lilly and Company, Emergent Biosolutions, Exelixis, Inc., Genevant Sciences, Inc., GlaxoSmithKline, Janssen Global Services, LLC., Medicago USA, Merck & Co. Inc., Moderna, Novavax, Regeneron Pharmaceuticals, Inc., Syneos Health, Valneva and Vyriad. Drs. Poland and Ovsyannikova hold patents related to measles, vaccinia, and influenza peptide vaccines. Drs. Poland and Kennedy hold a patent on vaccinia peptide research. Dr. Kennedy has received funding from Merck Research Laboratories to study waning immunity to measles and mumps after immunization with the MMR-II® vaccine. Drs. Poland, Kennedy, and Ovsyannikova have received grant funding from ICW Ventures for preclinical studies on a peptide-based COVID-19 vaccine. All other authors declare no competing financial interests. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policies., (© 2023 Published by Elsevier Ltd.)

Background: We have previously described genetic polymorphisms in candidate genes that are associated with inter-individual variations in antibody responses to mumps vaccination. To expand upon our previous work, we performed a genome-wide association study (GWAS) to discover host genetic variants associated with mumps vaccine-induced cellular immune responses., Methods: We performed a GWAS of mumps-specific immune response outcomes (11 secreted cytokines/chemokines) in a cohort of 1,406 subjects., Results: Among the 11 cytokine/chemokines we studied, four (IFN-γ, IL-2, IL-1β, and TNFα) demonstrated GWAS signals reaching genome-wide significance (p < 5 × 10 -8 ). A genomic region (encoding Sialic acid-binding immunoglobulin-type lectins/SIGLEC) located on chromosome 19q13 (p < 5 × 10 -8 ) was associated with both IL-1β and TNFα responses. The SIGLEC5/SIGLEC14 region contained 11 statistically significant single nucleotide polymorphisms (SNPs), including the intronic SIGLEC5 rs872629 (p = 1.3E-11) and rs1106476 (p = 1.32E-11) whose alternate alleles were significantly associated with decreased levels of mumps-specific IL-1β (rs872629, p = 1.77E-09; rs1106476, p = 1.78E-09) and TNFα (rs872629, p = 1.3E-11; rs1106476, p = 1.32E-11) production., Conclusions: Our results suggest that SNPs in the SIGLEC5/SIGLEC14 genes play a role in cellular and inflammatory immune responses to mumps vaccination. These findings motivate further research into the functional roles of SIGLEC genes in the regulation of mumps vaccine-induced immunity., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Poland is the chair of a Safety Evaluation Committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. Dr. Poland provides consultative advice on vaccine development to AiZtech, AstraZeneca UK Limited, Eli Lilly and Company, Emergent Biosolutions, Exelixis, Inc., Genevant Sciences, Inc., GlaxoSmithKline, Janssen Global Services, LLC., Medicago USA, Merck & Co. Inc., Moderna, Novavax, Regeneron Pharmaceuticals, Inc., Syneos Health, Valneva and Vyriad. Drs. Poland and Ovsyannikova hold patents related to measles, vaccinia, and influenza peptide vaccines. Drs. Poland and Kennedy hold a patent on vaccinia peptide research. Dr. Kennedy has received funding from Merck Research Laboratories to study waning immunity to measles and mumps after immunization with the MMR-II® vaccine. Drs. Poland, Kennedy, and Ovsyannikova have received grant funding from ICW Ventures for preclinical studies on a peptide-based COVID-19 vaccine. All other authors declare no competing financial interests. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policies. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Copyright © 2023. Published by Elsevier Ltd.)

Background: In the vaccine era, individuals receive multiple vaccines in their lifetime. Host gene expression in response to antigenic stimulation is usually virus-specific; however, identifying shared pathways of host response across a wide spectrum of vaccine pathogens can shed light on the molecular mechanisms/components which can be targeted for the development of broad/universal therapeutics and vaccines., Method: We isolated PBMCs, monocytes, B cells, and CD8 + T cells from the peripheral blood of healthy donors, who received both seasonal influenza vaccine (within <1 year) and smallpox vaccine (within 1 - 4 years). Each of the purified cell populations was stimulated with either influenza virus or vaccinia virus. Differentially expressed genes (DEGs) relative to unstimulated controls were identified for each in vitro viral infection, as well as for both viral infections (shared DEGs). Pathway enrichment analysis was performed to associate identified DEGs with KEGG/biological pathways., Results: We identified 2,906, 3,888, 681, and 446 DEGs in PBMCs, monocytes, B cells, and CD8 + T cells, respectively, in response to influenza stimulation. Meanwhile, 97, 120, 20, and 10 DEGs were identified as gene signatures in PBMCs, monocytes, B cells, and CD8 + T cells, respectively, upon vaccinia stimulation. The majority of DEGs identified in PBMCs were also found in monocytes after either viral stimulation. Of the virus-specific DEGs, 55, 63, and 9 DEGs occurred in common in PBMCs, monocytes, and B cells, respectively, while no DEGs were shared in infected CD8 + T cells after influenza and vaccinia. Gene set enrichment analysis demonstrated that these shared DEGs were over-represented in innate signaling pathways, including cytokine-cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptor, Toll-like receptor signaling, RIG-I-like receptor signaling pathways, cytosolic DNA-sensing pathways, and natural killer cell mediated cytotoxicity., Conclusion: Our results provide insights into virus-host interactions in different immune cells, as well as host defense mechanisms against viral stimulation. Our data also highlights the role of monocytes as a major cell population driving gene expression in ex vivo PBMCs in response to viral stimulation. The immune response signaling pathways identified in this study may provide specific targets for the development of novel virus-specific therapeutics and improved vaccines for vaccinia and influenza. Although influenza and vaccinia viruses have been selected in this study as pathogen models, this approach could be applicable to other pathogens., Competing Interests: Dr. GP offers consultative advice to Johnson & Johnson/Janssen Global Services LLC, and is the chair of a Safety Evaluation Committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. Dr. GP also offers consultative advice on vaccine development to Merck & Co Keniworth, NJ., Medicago Quebec City, Quebec, GlaxoSmithKline Brentford, United Kingdom, Sanofi Pasteur Lyon, France, Emergent Biosolutions Gaithersburg, MD, AstraZeneca Cambridge, United Kingdom, Janssen Beerse, Belgium, Vyriad Rochester, MN, Moderna Cambridge, MA. Drs. GP and IO hold patents related to vaccinia and measles peptide vaccines. Drs. RK, GP, and IO hold a patent related to vaccinia peptide vaccines. Drs. GP, RK, and IO have received grant funding and royalties from ICW Ventures for pre-clinical studies on a peptide-based COVID-19 vaccine. Drs. GP, RK, IO and IH hold a patent related to the impact of single nucleotide polymorphisms on measles vaccine immunity. Dr. RK has received funding from Merck Research Laboratories to study waning immunity to mumps vaccine. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policy. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Quach, Goergen, Grill, Haralambieva, Ovsyannikova, Poland and Kennedy.)

Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Hamburg reports no competing interests. Dr. Poland declares the following interests: Dr. Poland offers consultative advice on COVID-19 vaccine development to AstraZeneca, Pfizer, Medicago, Johnson&Johnson/Janssen, Novavax, and Moderna. Dr. Poland also has received grant funding from ICW Ventures for preclinical studies on a peptide-based COVID-19 vaccine for which he holds a patent. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies.