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The ethical debate over mandatory healthcare worker (HCW) influenza vaccination is a heated one. Our study hospital instituted a mandatory employee influenza vaccination policy for the 2009-2010 influenza season during the highly publicized pandemic of the H1N1 "Swine Flu." Under this mandate there was no informed declination option, and termination of employment was the consequence for noncompliance. Our objective was to examine HCW perceptions of the H1N1 influenza virus, the vaccine, and the strict mandated vaccination policy. A survey was designed, distributed, and anonymously collected. In total, 202 completed questionnaires were obtained via accidental sampling by the investigators achieving a 100% response rate. Data analysis showed that 31.7% of surveyed HCWs felt the mandate was an infringement on their rights and 3.5% of HCWs would electively seek employment elsewhere. Significantly more nurses and clerks/technicians were opposed to the mandate compared to other types of employees. 96% felt that the mandating hospital should be liable should a significant adverse effect occur from receiving the vaccine. While the mandate helped to increase HCW influenza vaccination rates dramatically, the strict consequence of employment termination created negative feelings of coercion. Adopting a policy that includes a declination option with mandatory masking during influenza season might be a more widely acceptable and still adequate approach., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

• Vaccination acceptability decreased from 91.1% in 2000 to 61.2% in 2010. • Vaccination acceptability increased during the COVID-19 pandemic. • Higher acceptability among persons with higher incomes and education levels. • Widening social and economic gap in terms of vaccine acceptability over time. This study describes the evolution of vaccination acceptability and associated determinants in the French general population between 2000 and 2021, and vaccinations with the highest vaccine hesitancy between 2010 and 2021. Data were collected from the nine national 'Health Barometer' cross-sectional surveys conducted between 2000 and 2021. These surveys included French-speaking individuals aged 18–75 years old who were selected through randomly generated landline and mobile phone numbers. Participants were asked about their acceptability of vaccination in general and their vaccine hesitancy toward any particular vaccinations. Determinants of vaccination acceptability were studied using univariate and multivariate Poisson regressions. The proportion of persons who found vaccination acceptable in general (i.e., answering "very" or "somewhat" favourable in the survey interview) decreased from 91.1% in 2000 to 61.2% in 2010 (the latter year coinciding with the 2009 H1N1 influenza pandemic), increased in 2014 (78.8%), slightly fluctuated until 2019 (74.2%), and increased again in both 2020 (80.0%) and 2021 (82.5%) during the COVID-19 pandemic. Irrespective of the year, acceptability was higher among persons with higher incomes, those with a higher education level, and individuals not living alone. In 2021, for the first time, vaccination acceptability was higher among persons over 44 years old (versus 18–24 year-olds) and among retired persons (versus workers). The highest hesitancy rate for a vaccine was for the 2009 H1N1 influenza virus in 2010 (41% answering "somewhat" or "very" unfavourable). In 2021, the highest rate was for the COVID-19 vaccine (21%). Unlike the experience of the 2009 AH1N1 influenza pandemic, which led to a collapse in vaccination acceptability among the French general population, acceptability continued to increase during the COVID-19 pandemic. However, the pre-2010 level was not reached. Our results show a tendency towards a widening social and economic gap in terms of vaccine acceptability over time. [ABSTRACT FROM AUTHOR]

• Acute and past helminth infection suppress antibody responses to influenza vaccination. • Vaccine-induced protection against an influenza challenge infection is abrogated in helminth-infected mice. • Suppressed vaccination efficacy is associated with a systemic and sustained expansion of Tr1 cells. • Implementation of adjuvanted or prime-boost vaccination does not restore vaccination efficacy. • Drug induced deworming does not restore vaccination efficacy. Helminth parasites infect more than a quarter of the human population and inflict significant changes to the immunological status of their hosts. Several human studies report impaired responses to vaccinations in helminth-infected individuals. Analysing the impact of helminth infections on the efficacy of influenza vaccinations in the mouse system helps to elucidate the underlying immunological processes. Concurrent infection with the parasitic nematode Litomosoides sigmodontis reduced the quantity and quality of antibody responses to vaccination against seasonal influenza in BALB/c and C57BL/6 mice. This led to impaired vaccination-induced protection against challenge infections with the human pathogenic 2009 pandemic H1N1 influenza A virus in helminth-infected mice. Impaired responses were also observed if vaccinations were performed after immune-driven or drug-induced clearance of a previous helminth infection. Mechanistically, the suppression was associated with a systemic and sustained expansion of IL-10-producing CD4+CD49b+LAG-3+ type 1 regulatory T cells and partially abrogated by in vivo blockade of the IL-10 receptor. In summary, these findings raise the concern that individuals in helminth-endemic areas may not always benefit from vaccinations, even in the absence of an acute and diagnosable helminth infection. [ABSTRACT FROM AUTHOR]

The influenza neuraminidase (NA) is a promising target for next-generation vaccines. Protection induced by vaccination with the computationally optimized broadly reactive NA antigen (N1-I COBRA NA) was characterized in both influenza serologically naive and pre-immune ferret models following H1N1 (A/California/07/2009, CA/09) or H5N1 (A/Vietnam/1203/2004, Viet/04) influenza challenges. The N1-I COBRA NA vaccine elicited antibodies with neutralizing ELLA activity against both seasonal and pandemic H1N1 influenza, as well as the H5N1 influenza virus. In both models, N1-I COBRA NA-vaccinated ferrets that were challenged with CA/09 virus had similar morbidity (weight loss and clinical symptoms) as ferrets vaccinated with the CA/09 HA control vaccine. There were significantly reduced viral titers compared to the mock-vaccinated control animals. Ferrets vaccinated with N1-I COBRA NA or Viet/04 NA vaccines were protected against the H5N1 virus infection with minimal clinical symptoms and negligible weight loss. In contrast, ferrets vaccinated with the CA/09 NA vaccine lost ~10% of their original body weight with 25% mortality. Vaccination with either HA or NA vaccines did not inhibit contact transmission of CA/09 virus to naïve cage mates. Overall, the N1-I COBRA vaccine elicited protective immune responses against both H1N1 and H5N1 infections and partially mitigated disease in contact-transmission receiving ferrets. These results indicate that the N1-I COBRA NA performed similarly to the CA/09 HA and NA positive controls. Therefore, the N1-I COBRA NA alone induces protection against viruses from both H5N1 and H1N1 subtypes, indicating its value as a vaccine component in broadly protective influenza vaccines. [ABSTRACT FROM AUTHOR]

This report surveyed vaccination decisions during pregnancy based on the package inserts of vaccines approved in Japan, the USA, and Europe. Furthermore, it evaluates vaccination decision-making factors based on the characteristics of the target infections and the modality of the vaccines. Live vaccines known to cause fetal abnormalities are contraindicated for pregnant women, whereas vaccines for life-threatening infectious diseases are authorized for administration during pregnancy when the need is recognized, even for live vaccines. We compared the World Health Organization and European Medicines Agency guidelines on the development of vaccines for pregnant women and surveyed the details of the studies to collect information on SARS-CoV-2 vaccination during pregnancy. In compliance with the guidelines, for all SARS-CoV-2 vaccines, non-clinical reproductive and developmental toxicity studies and clinical trials including non-pregnant women of childbearing age were conducted prior to the vaccination of pregnant women. For all vaccines, information from registries on vaccination during pregnancy are used for post-marketing surveillance. While it is desirable to vaccinate women before pregnancy through planned immunization, whenever possible, pandemics such as H1N1 influenza and COVID-19 may require vaccination even during pregnancy. Necessary and sufficient studies for the decision of vaccination during pregnancy should be carried out promptly. [ABSTRACT FROM AUTHOR]

Swine influenza viruses (SIV) produce a highly contagious and worldwide distributed disease that can cause important economic losses to the pig industry. Currently, this virus is endemic in farms and, although used limitedly, trivalent vaccine application is the most extended strategy to control SIV. The presence of pre-existing immunity against SIV may modulate the evolutionary dynamic of this virus. To better understand these dynamics, the viral variants generated in vaccinated and nonvaccinated H3N2 challenged pigs after recovery from a natural A(H1N1) pdm09 infection were determined and analyzed. In total, seventeen whole SIV genomes were determined, 6 from vaccinated, and 10 from nonvaccinated animals and their inoculum, by NGS. Herein, 214 de novo substitutions were found along all SIV segments, 44 of them being nonsynonymous ones with an allele frequency greater than 5%. Nonsynonymous substitutions were not found in NP; meanwhile, many of these were allocated in PB2, PB1, and NS1 proteins. Regarding HA and NA proteins, higher nucleotide diversity, proportionally more nonsynonymous substitutions with an allele frequency greater than 5%, and different domain allocations of mutants, were observed in vaccinated animals, indicating different evolutionary dynamics. This study highlights the rapid adaptability of SIV in different environments. [ABSTRACT FROM AUTHOR]

Aims: To study incident narcolepsy in first‐ and second‐generation immigrant groups using Swedish‐born individuals and native Swedes as referents. Methods: The study population included all individuals registered and alive in Sweden at baseline. Narcolepsy was defined as having at least one registered diagnosis of narcolepsy in the Swedish National Patient Register. The incidence of narcolepsy in different immigrant groups was assessed by Cox regression, with hazard ratios (HRs) and 95% confidence intervals (CI). The models were stratified by sex and adjusted for age, geographical residence in Sweden, educational level, marital status, co‐morbidities, and neighbourhood socioeconomic status. Results: In the first‐generation study, 1225 narcolepsy cases were found; 465 males and 760 females, and in the second‐generation study, 1710 cases, 702 males and 1008 females. Fully adjusted HRs (95% CI) in the first‐generation study was for males 0.83 (0.61–1.13) and females 0.83 (0.64–1.07), and in the second‐generation study for males 0.76 (0.60–0.95) and females 0.91 (95% CI 0.76–1.09). Statistically significant excess risks of narcolepsy were found in first‐generation males from North America, and second‐generation males with parents from North America, and second‐generation females with parents from Latin America. Conclusions: There were only significant differences in incident narcolepsy between native Swedes and second‐generation male immigrants. The observed differences can partly be explained by differences in Pandemrix® vaccinations and are probably not attributable to genetic differences between immigrants and natives. [ABSTRACT FROM AUTHOR]

To evaluate class suspension and mass vaccination implemented among Taipei schoolchildren during the 2009 influenza pandemic and investigate factors affecting antibody responses. We conducted 2 cohort studies on: (1) 972 schoolchildren from November 2009–March 2010 to evaluate pandemic policies and (2) 935 schoolchildren from November 2011–March 2012 to verify factors in antibody waning. Anti-influenza H1N1pdm09 hemagglutination inhibition antibodies (HI-Ab) were measured from serum samples collected before vaccination, and at 1 and 4 months after vaccination. Factors affecting HI-Ab responses were investigated through logistic regression and generalized estimating equation. Seroprevalence of H1N1pdm09 before vaccination was significantly higher among schoolchildren who experienced class suspensions than those who did not (59.6% vs 47.5%, p<0.05). Participating in after-school activities (adjusted odds ratio [aOR]=2.47, p=0.047) and having ≥3 hours per week of exercise (aOR=2.86, p=0.019) were significantly correlated with H1N1pdm09 infection. Two doses of the H1N1pdm09 vaccine demonstrated significantly better antibody persistence than 1 dose (HI-Ab geometric mean titer: 132.5 vs 88.6, p=0.047). Vaccine effectiveness after controlling for preexisting immunity was 86% (32%-97%). Exercise ≥3 hours per week and preexisting immunity were significantly associated with antibody waning/maintenance. This study is the first to show that exercise and preexisting immunity may affect antibody waning. Further investigation is needed to identify immune correlates of protection. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and seasonal influenza viruses are cocirculating in the human population. However, only a few cases of viral coinfection with these two viruses have been documented in humans with some people having severe disease and others mild disease. To examine this phenomenon, ferrets were coinfected with SARS-CoV-2 and human seasonal influenza A viruses (IAVs; H1N1 or H3N2) and were compared to animals that received each virus alone. Ferrets were either immunologically naive to both viruses or vaccinated with the 2019 to 2020 split-inactivated influenza virus vaccine. Coinfected naive ferrets lost significantly more body weight than ferrets infected with each virus alone and had more severe inflammation in both the nose and lungs compared to that of ferrets that were single infected with each virus. Coinfected, naive animals had predominantly higher IAV titers than SARS-CoV-2 titers, and IAVs were efficiently transmitted by direct contact to the cohoused ferrets. Comparatively, SARS-CoV-2 failed to transmit to the ferrets that cohoused with coinfected ferrets by direct contact. Moreover, vaccination significantly reduced IAV titers and shortened the viral shedding but did not completely block direct contact transmission of the influenza virus. Notably, vaccination significantly ameliorated influenza-associated disease by protecting vaccinated animals from severe morbidity after IAV single infection or IAV and SARS-CoV-2 coinfection, suggesting that seasonal influenza virus vaccination is pivotal to prevent severe disease induced by IAV and SARS-CoV-2 coinfection during the COVID-19 pandemic. IMPORTANCE Influenza A viruses cause severe morbidity and mortality during each influenza virus season. The emergence of SARS-CoV-2 infection in the human population offers the opportunity to potential coinfections of both viruses. The development of useful animal models to assess the pathogenesis, transmission, and viral evolution of these viruses as they coinfect a host is of critical importance for the development of vaccines and therapeutics. The ability to prevent the most severe effects of viral coinfections can be studied using effect coinfection ferret models described in this report. [ABSTRACT FROM AUTHOR]

Helminths still infect a quarter of the human population. They manage to establish chronic infections by downmodulating the immune system of their hosts. Consequently, the immune response of helminth-infected individuals to vaccinations may be impaired as well. Here we study the impact of helminth-induced immunomodulation on vaccination efficacy in the mouse system. We have previously shown that an underlying Litomosoides sigmodontis infection reduced the antibody (Ab) response to anti-influenza vaccination in the context of a systemic expansion of type 1 regulatory T cells (Tr1). Most important, vaccine-induced protection from a challenge infection with the 2009 pandemic H1N1 influenza A virus (2009 pH1N1) was impaired in vaccinated, L. sigmodontis- infected mice. Here, we aim at the restoration of vaccination efficacy by drug-induced deworming. Treatment of mice with Flubendazole (FBZ) resulted in elimination of viable L. sigmodontis parasites in the thoracic cavity after two weeks. Simultaneous FBZ-treatment and vaccination did not restore Ab responses or protection in L. sigmodontis- infected mice. Likewise, FBZ-treatment two weeks prior to vaccination did not significantly elevate the influenza-specific Ig response and did not protect mice from a challenge infection with 2009 pH1N1. Analysis of the regulatory T cell compartment revealed that L. sigmodontis- infected and FBZ-treated mice still displayed expanded Tr1 cell populations that may contribute to the sustained suppression of vaccination responses in successfully dewormed mice. To outcompete this sustained immunomodulation in formerly helminth-infected mice, we finally combined the drug-induced deworming with an improved vaccination regimen. Two injections with the non-adjuvanted anti-influenza vaccine Begripal conferred 60% protection while MF59-adjuvanted Fluad conferred 100% protection from a 2009 pH1N1 infection in FBZ-treated, formerly L. sigmodontis- infected mice. Of note, applying this improved prime-boost regimen did not restore protection in untreated L. sigmodontis- infected mice. In summary our findings highlight the risk of failed vaccinations due to helminth infection. [ABSTRACT FROM AUTHOR]

Background: In 2009, a novel influenza A/H1N1pdm09 emerged and caused a pandemic. This strain continued to circulate and was therefore included in the seasonal vaccines up to the 2016/2017-season. This provided a unique opportunity to study the long-term antibody responses to H1N1pdm09 in healthcare workers (HCW) with a different vaccination history. Methods: HCW at Haukeland University Hospital, Bergen, Norway were immunized with the AS03-adjuvanted H1N1pdm09 vaccine in 2009 (N=55) and divided into groups according to their vaccination history; one vaccination (N=10), two vaccinations (N=15), three vaccinations (N=5), four vaccinations (N=15) and five vaccinations (N=10). HCW are recommended for influenza vaccination to protect both themselves and their patients, but it is voluntary in Norway. Blood samples were collected pre- and at 21 days, 3, 6, and 12 months after each vaccination, or annually from 2010 HCW without vaccination. ELISA, haemagglutination inhibition (HI) and microneutralization (MN) assays were used to determine the antibody response. Results: Pandemic vaccination induced a significant increase in the H1N1-specific antibodies measured by ELISA, HI and MN. Seasonal vaccination boosted the antibody response, both in HCW with only the current vaccination and those with prior and current vaccination during 2010/11-2013/14. We observed a trend of increased antibody responses in HCW with only the current vaccination in 2013/14. A two- and three-year gap before vaccination in 2013/14 provided a more potent antibody response compared to annually vaccinated HCW. Conclusions: Our long term follow up study elucidates the antibody response in HCW with different vaccination histories. Our findings contribute to our understanding of the impact of repeated vaccination upon antibody responses. [ABSTRACT FROM AUTHOR]

Interleukin-33 (IL-33) is a multifunctional cytokine that mediates type 2-dominated immune responses. In contrast, the role of IL-33 during viral vaccination, which often aims to induce type 1 immunity, has not been fully investigated. Here, we examined the effects of IL-33 on influenza vaccine responses. We found that intranasal coadministration of IL-33 with an inactivated influenza virus vaccine increases vaccine efficacy against influenza virus infection, not only with the homologous strain but also with heterologous strains, including the 2009 H1N1 influenza virus pandemic strain. Cross-protection was dependent on group 2 innate lymphoid cells (ILC2s), as the beneficial effect of IL-33 on vaccine efficacy was abrogated in ILC2-deficient C57BL/6 Il7rCre/+ Rorafl/fl mice. Furthermore, mechanistic studies revealed that IL-33-activated ILC2s potentiate vaccine efficacy by enhancing mucosal humoral immunity, particularly IgA responses, potentially in a Th2 cytokine-dependent manner. Our results demonstrate that IL-33-mediated activation of ILC2s is a critical early event that is important for the induction of mucosal humoral immunity, which in turn is responsible for cross-strain protection against influenza. Thus, we reveal a previously unrecognized role for the IL-33-ILC2 axis in establishing broadly protective and long-lasting humoral mucosal immunity against influenza, knowledge that may help in the development of a universal influenza vaccine. [ABSTRACT FROM AUTHOR]

Gene expression data is commonly used in vaccine studies to characterize differences between treatment groups or sampling time points. Group-wise comparisons of the transcriptional perturbations induced by vaccination have been applied extensively for investigating the mechanisms of action of vaccines. Such approaches, however, may not be sensitive enough for detecting changes occurring within a minority of the population under investigation or in single individuals. In this study, we developed a data analysis framework to characterize individual subject response profiles in the context of repeated measure experiments, which are typical of vaccine mode of action studies. Following the definition of the methodology, this was applied to the analysis of human transcriptome responses induced by vaccination with a subunit influenza vaccine. Results highlighted a substantial heterogeneity in how different subjects respond to vaccination. Moreover, the extent of transcriptional modulation experienced by each individual subject was found to be associated with the magnitude of vaccine-specific functional antibody response, pointing to a mechanistic link between genes involved in protein production and innate antiviral response. Overall, we propose that the improved characterization of the intersubject heterogeneity, enabled by our approach, can help driving the improvement and optimization of current and next-generation vaccines. [ABSTRACT FROM AUTHOR]

Study Objectives: Evidence suggests a cell-mediated autoimmune pathogenesis for narcolepsy type 1 (NT1), but it is not clear whether the disease is associated with overall changes in T cell subsets. The increase in NT1 incidence after H1N1 vaccination campaign with the Pandemrix™ vaccine suggests that disease-relevant changes in the immune system following this vaccination were important. In this study, we aimed to investigate differentiated T cell subsets and levels of CD25 and CD69 activation markers in a cohort of mainly Pandemrix™-vaccinated NT1 patients compared with their vaccinated and unvaccinated siblings.Methods: Peripheral blood mononuclear cells were collected in parallel and analysed with flow cytometry in 31 NT1 patients with disease onset after the 2009 influenza A (H1N1) pandemic and/or Pandemrix™ vaccination and 45 of their non-narcoleptic siblings (29/31 and 34/45 vaccinated, respectively).Results: We observed significantly lower effector memory CD4+ T cell levels in NT1 patients compared to their siblings, when controlling for HLA DQB1∗06:02 and vaccination status. Further, within the sibling group, vaccination status significantly affected frequencies of central memory and CD8+CD25+ T cells, and HLA DQB1∗06:02 status significantly affected frequencies of CD4+CD25+ T cells.Conclusion: We confirm that NT1 is associated with lower levels of effector memory CD4+ T cells in peripheral blood. Importantly, this finding was only significant when controlling for vaccination and HLA status in both patients and controls. We thus demonstrate the importance of characterizing such factors (eg HLA and vaccination) when studying T cell subsets in NT1. This might explain earlier conflicting results. [ABSTRACT FROM AUTHOR]

Management of novel viral respiratory disease outbreak on-board a ship with person-to-person transmission can be a public health challenge because of close proximity of inhabitants due to confined space and air-conditioned environment. It has a potential to be explosive, with high secondary attack rate (SAR) and cause significant morbidity and mortality. This study compares control measures instituted on-board two ships with similar outbreaks and recommends a standardized evidence-based outbreak response against them. This is a descriptive study, showing comparative analysis of control measures instituted on-board two ships, a cruise ship in case of COVID-19 and a warship in case of H1N1 influenza, with novel viral respiratory disease outbreak, at different span of time. Data of the date of onset, clinical details, laboratory results, history of travel, history of contact with positive case and control measures initiated were collected, analysed and compared. Of the two ships compared, one was a cruise ship with 712 COVID-19 cases, with an attack rate (AR) of 19.2% and 13 deaths, and other a warship with 14 cases of H1N1 influenza and an AR of 4.83%. The epidemic curve for both the outbreaks was plotted to study time distribution. Active surveillance, early self-reporting and immediate disembarkation of the suspects, along with strict compliance of hand hygiene, cough etiquettes and disinfection enhancement, will help in early mitigation of the outbreak. Health education should be undertaken to impart evidence-based knowledge and alleviate fear of the unknown. Vaccination may not be present but if available should only be administered after strict risk–benefit, cost–benefit and effectiveness analysis. [ABSTRACT FROM AUTHOR]

The modulation of the transcriptome is among the earliest responses to infection. However, defining the transcriptomic signatures of disease is challenging because logistic, technical, and cost factors limit the size and representativeness of samples in clinical studies. These limitations lead to a poor performance of signatures when applied to new datasets. Although the study focuses on infection, the central hypothesis of the work is the generalization of sets of signatures across diseases. We use a machine learning approach to identify common elements in datasets and then test empirically whether they are informative about a second dataset from a disease or process distinct from the original dataset. We identify sets of genes, which we name transfer signatures, that are predictive across diverse datasets and/or species (e.g., rhesus to humans). We demonstrate the usefulness of transfer signatures in two use cases: the progression of latent to active tuberculosis and the severity of COVID-19 and influenza A H1N1 infection. This indicates that transfer signatures can be deployed in settings that lack disease-specific biomarkers. The broad significance of our work lies in the concept that a small set of archetypal human immunophenotypes, captured by transfer signatures, can explain a larger set of responses to diverse diseases. [ABSTRACT FROM AUTHOR]

Prior research has highlighted racial and ethnic disparities in H1N1 vaccination in the United States. Our study adds to this literature by utilizing an intersectionality framework to examine the joint influence of race and sex on H1N1 vaccination beliefs and behaviors among non-Hispanic blacks and non-Hispanic whites (hereafter blacks and whites). Using data from the National H1N1 Flu Survey of U.S. adults, we measured differences in beliefs about the safety and efficacy of the H1N1 vaccine among black women, black men, white women, and white men. We then estimated a series of nested logistic regression models to examine how race/sex vaccination disparities were influenced by health beliefs, socioeconomic status (SES), pre-existing conditions, and healthcare. Black respondents were more likely than white respondents to express reservations about the safety and efficacy of the H1N1 vaccine. Consistent with those beliefs, white females reported the highest rate of H1N1 vaccination (28.4%), followed by white males (26.3%), black males (21.6%), and black females (17.5%). Differences in health beliefs, SES, pre-existing conditions, and healthcare explained lower odds of H1N1 vaccination among white men and black men, relative to white women. However, black women experienced 35–45% lower odds of vaccination than white women across all models, highlighting the intersectional nature of these associations. The 2009 H1N1 influenza pandemic provides a cautionary tale about the distribution of new vaccines across large populations with diverse racial, sex, and socioeconomic characteristics. Despite differences between the H1N1 and COVID-19 pandemics, our study warns that many black Americans will forego COVID-19 vaccines unless swift action is taken to address black-white disparities in access to vital resources. Public health stakeholders can also encourage widespread adoption of COVID-19 vaccines by tailoring health promotion messages for different groups of racial minorities, especially groups like black women who face intersecting disadvantages. [ABSTRACT FROM AUTHOR]

Influenza is a highly contagious, acute respiratory viral infection responsible for annual epidemics causing severe morbidity and mortality. Vaccination remains the most effective, live-saving preventative strategy, especially amongst populations at high risk of developing influenza-related complications. The inactivated trivalent seasonal influenza vaccine contains two World Health Organization (WHO)-recommended influenza A and one influenza B strains, while the quadrivalent vaccine contains an additional B strain, providing broader protection against co-circulating influenza B lineages. Healthcare workers are instrumental in ensuring effective communication about the benefits of influenza vaccination to achieve optimal seasonal influenza vaccination coverage. This article provides an updated overview of the influenza vaccines with special consideration of the current COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

• About two thirds of caregivers intend to vaccinate their children against COVID-19. • Most common reason for acceptance was to protect the child. • Most common reason for refusal was the vaccine's novelty. • Child age, chronic illness, vaccination history affects willingness. • Caregiver gender, vaccination history, concern about infection affect willingness. More than 100 COVID-19 vaccine candidates are in development since the SARS-CoV-2 genetic sequence was published in January 2020. The uptake of a COVID-19 vaccine among children will be instrumental in limiting the spread of the disease as herd immunity may require vaccine coverage of up to 80% of the population. Prior history of pandemic vaccine coverage was as low as 40% among children in the United States during the 2009 H1N1 influenza pandemic. To investigate predictors associated with global caregivers' intent to vaccinate their children against COVID-19, when the vaccine becomes available. An international cross sectional survey of 1541 caregivers arriving with their children to 16 pediatric Emergency Departments (ED) across six countries from March 26 to May 31, 2020. 65% (n = 1005) of caregivers reported that they intend to vaccinate their child against COVID-19, once a vaccine is available. A univariate and subsequent multivariate analysis found that increased intended uptake was associated with children that were older, children with no chronic illness, when fathers completed the survey, children up-to-date on their vaccination schedule, recent history of vaccination against influenza, and caregivers concerned their child had COVID-19 at the time of survey completion in the ED. The most common reason reported by caregivers intending to vaccinate was to protect their child (62%), and the most common reason reported by caregivers refusing vaccination was the vaccine's novelty (52%). The majority of caregivers intend to vaccinate their children against COVID-19, though uptake will likely be associated with specific factors such as child and caregiver demographics and vaccination history. Public health strategies need to address barriers to uptake by providing evidence about an upcoming COVID-19 vaccine's safety and efficacy, highlighting the risks and consequences of infection in children, and educating caregivers on the role of vaccination. [ABSTRACT FROM AUTHOR]

Objective: H1N1/09 was the first pandemic flu ever responded to with mass vaccinations. Public health nurses (PHNs) were pivotal in implementing the H1N1/09 vaccination clinics. With the ongoing threat of pandemic influenza and other viral outbreaks, much can be learned from these PHNs' H1N1/09 experiences. This study's purpose was to explore PHNs' experiences in the H1N1/09 mass vaccination clinics. Design and Sample: In a qualitative interpretive description, 23 PHNs (16 immunizers, seven supervisors) who worked in a large Canadian municipal public health agency, participated in semistructured interviews. Results: Three overarching themes were identified. 'Anticipating an Emergency' discusses participants' experiences learning about the pandemic response and their role preparation. 'Surviving the Chaos' reflects the challenges of the clinics, particularly during the first few hectic weeks of the response. 'Persevering Over Time' encompasses participants' experiences as they became familiar with clinics' operations and their own responsibilities. Conclusions: Participants' experiences have implications for future public health pandemic planning and research. Key recommendations include to communicate with PHNs in a timely manner about their clinic roles, and to provide PHNs with appropriate training to optimize clinics' operations. This will help support PHNs in their roles to protect the public and provide quality population care. [ABSTRACT FROM AUTHOR]

Background Although high-dose (HD) vaccines have been reported to stimulate higher antibody responses compared with standard-dose (SD) influenza vaccines, there have been limited studies on the impact of frailty on such responses. Methods We conducted a randomized, double-blind trial (2014/2015 to 2017/2018) of SD versus HD trivalent split-virus vaccine (Fluzone) in 612 study participants aged 65+ over 4 influenza seasons. Hemagglutination inhibition antibody titers for influenza H1N1, H3N2, and B vaccine subtypes were measured at baseline and at 4, 10, and 20 weeks postvaccination and frailty was measured using a validated frailty index. Results Geometric mean antibody titers were significantly higher in HD compared with SD vaccine recipients for all influenza subtypes at all time points postvaccination. However, frailty was positively correlated with 4-week titers and was associated with increased odds of being a vaccine responder. For influenza A subtypes, this was mostly limited to HD recipients. Conclusions Frailty was associated with higher titers and increased antibody responses at 4 weeks after influenza vaccination, which was partially dependent on vaccine dosage. Chronic inflammation or dysregulated immunity, both of which are commonly observed with frailty, may be responsible, but it requires further investigation. [ABSTRACT FROM AUTHOR]

• National survey of obstetricians' experiences with influenza-related media reports. • Decreased effectiveness, purported risk of miscarriage, and severe influenza season. • Many unaware of purported increased risk of miscarriage study. • Most continued to strongly recommend influenza vaccine despite negative reports. In 2017, three media stories regarding influenza vaccine may have impacted obstetricians' (OB) influenza vaccination practices: reports of reduced influenza vaccine effectiveness, a severe influenza season, and a possible increased risk of miscarriage among pregnant women receiving 2009 H1N1 vaccine in the 1st trimester who had received H1N1 vaccine the previous season (later disproven). Describe OB's: (1) awareness of; (2) attitudes and experiences related to; and (3) reported alterations in practice as a result of these reports. A survey among a nationally representative sample of OBs April to June 2018. Response rate was 65% (302/468). 88% of OBs were "very aware" of the severe season, 74% of lower effectiveness, and 25% of the miscarriage study (47% "completely unaware" of miscarriage study). Among those aware, 58%, 57%, and 16% reported ≥10% of pregnant patients initiated discussions about the severe season, lower effectiveness, and miscarriage study, respectively. Most (83%) agreed reports about increased severity increased their enthusiasm for recommending influenza vaccine; fewer agreed reports about the miscarriage study (18%) and lower vaccine effectiveness (12%) decreased their enthusiasm for recommending influenza vaccine. Providers were more likely to initiate discussion with patients about increased severity of the season than the other reports. However, 35% agreed the miscarriage study reports increased their concerns about influenza vaccine safety; 18% (n = 48) reported changing the way they recommended influenza vaccine. Of those, 17 (6% of all respondents) reported not recommending influenza vaccine to women during the 1st trimester and 26 (10% of all respondents) recommended it but were willing to delay until the 2nd trimester. During a season in which media stories could have influenced OB influenza vaccination behaviors in different directions, reports underscoring importance of influenza vaccine may have had more impact on OBs' recommendations than reports questioning vaccine safety or effectiveness. [ABSTRACT FROM AUTHOR]

In light of the limited protection conferred by current influenza vaccines, immunisation using universal influenza vaccines has been proposed for protection against all or most influenza sub-types. The fundamental principle of universal influenza vaccines is based on conserved antigens found in most influenza strains, such as matrix 2, nucleocapsid, matrix 1 and stem of hemagglutinin proteins. These antigens trigger cross-protective immunity against different influenza strains. Many researchers have attempted to produce the conserved epitopes of these antigens in the form of peptides in the hope of generating universal influenza vaccine candidates that can broadly induce cross-reactive protection against influenza viral infections. However, peptide vaccines are poorly immunogenic when applied individually owing to their small molecular sizes. Hence, strategies, such as combining peptides as multi-epitope vaccines or presenting peptides on vaccinia virus particles, are employed. This review discusses the clinical and laboratory findings of several multi-epitope peptide vaccine candidates and vaccinia-based peptide vaccines. The majority of these vaccine candidates have reached the clinical trial phase. The findings in this study will indeed shed light on the applicability of universal influenza vaccines to prevent seasonal and pandemic influenza outbreaks in the near future. [ABSTRACT FROM AUTHOR]

This article discusses a study of flu vaccine uptake and hesitancy in a rural community during the 2009–2010 H1N1 pandemic flu season. In it, we explore study participants' understanding of the relationship between vaccines, illness, and immunity, as well as parent intentionality in accepting or forgoing flu vaccines for their children. Our research offers novel conclusions about how people respond to the development and implementation of vaccines for newly emerging flu strains and establishes a warrant for qualitative research on vaccination practices that attends to participants' views about vaccines in the context of their overall ideas about health. Our findings suggest that more accurate understandings of people's beliefs and experiences of vaccination can be developed through qualitative research that values vernacular discourse. Our findings also suggest that influenza vaccination provides a fruitful context in which to study vaccine hesitancy and refusal. Finally, our study demonstrates that vaccine concerns are more demographically widespread than is presumed by current research. [ABSTRACT FROM AUTHOR]

Background: Human influenza virus infections cause a considerable burden of morbidity and mortality worldwide each year. Understanding regional influenza‐associated outpatient burden is crucial for formulating control strategies against influenza viruses. Methods: We extracted the national sentinel surveillance data on outpatient visits due to influenza‐like‐illness (ILI) and virological confirmation of sentinel specimens from 30 provinces of China from 2006 to 2015. Generalized additive regression models were fitted to estimate influenza‐associated excess ILI outpatient burden for each individual province, accounting for seasonal baselines and meteorological factors. Results: Influenza was associated with an average of 2.5 excess ILI consultations per 1000 person‐years (py) in 30 provinces of China each year from 2006 to 2015. Influenza A(H1N1)pdm09 led to a higher number of influenza‐associated ILI consultations in 2009 across all provinces compared with other years. The excess ILI burden was 4.5 per 1000 py among children aged below 15 years old, substantially higher than that in adults. Conclusions: Human influenza viruses caused considerable impact on population morbidity, with a consequent healthcare and economic burden. This study provided the evidence for planning of vaccination programs in China and a framework to estimate burden of influenza‐associated outpatient consultations. [ABSTRACT FROM AUTHOR]

Background: Several European countries have observed an association between narcolepsy and H1N1 vaccines containing AS03® adjuvant in children/adolescents. In Taiwan, a nationwide campaign starting November 2009 administered H1N1 vaccines without adjuvant or with MF59® adjuvant to 67% of children and 12% of adults.Methods: For those registered in the 2000-2012 National Health Insurance (NHI) databases, we compared age-stratified (0-4, 5-18, 19-59, and ≥60 years) incidence of first referral for a diagnostic MSLT for the pre-pandemic, pandemic/pre-vaccination, and vaccination/post-pandemic period. We also compared the odds of H1N1 vaccination in each chart-ascertained narcolepsy patient, whoever had an onset of excessive daytime sleepiness between April 2009 and December 2012, with 10 population-based controls from the NHI databases on year of birth, sex, and index date, using conditional logistic regressions.Results: Incidence of MSLT referral for narcolepsy was highest and significantly increased in the pandemic/pre-vaccination period in the age group 5-18 (IRR 3.40, 95% confidence intervals (CI) 2.12-5.45) and 19-59 (IRR 2.90, 95% CI 1.62-5.02) years. Among 137 confirmed narcolepsy cases (86 adults and 51 children), the odds ratios (ORs) were 1.67 (95% CI 0.81-3.45) (adults) and 1.22 (95% CI 0.62-2.39) (children) for H1N1 vaccination without adjuvant, and 1.39 (95% CI 0.17-11.48) (adults) and 3.66 (95% CI 0.37-36.02) (children) with MF59® adjuvant.Conclusion: No substantial association between the use of H1N1 vaccines and narcolepsy was identified in Taiwan. Instead, the H1N1 infection itself could have played a role in triggering narcolepsy in children and young adults. [ABSTRACT FROM AUTHOR]

To assess the immunogenicity and safety of vaccination against seasonal influenza in psoriatic arthritis (PsA) patients treated with secukinumab versus healthy controls (HC). PsA patients administered secukinumab for ≥3 months and HC received the Sanofi Pasteur vaccine composed of 3 antigens (H3N3, H1N1, and B) and underwent clinical and laboratory assessments on the day of vaccination and 4–6 weeks later. Immunogenicity of the vaccine was evaluated by hemagglutination inhibition assay against those 3 antigens. Responders to each antigen were defined by a 4-fold increase in the antigen titer or by seroconversion in patients whose baseline level was <1/40. Thirty-two consecutive PsA patients treated with secukinumab for ≥3 months comprised the study group, 10 of whom received concomitant conventional synthetic disease-modifying drugs, mostly methotrexate. There were 17 age- and gender-matched HC (median age 48.5 years, 6 females). The geometric mean titers of each antigen increased significantly in both groups. The number of responders in each group was similar for H3N2 and H1N1, and significantly higher for B/Brisbane in the PsA group. The proportion of patients with a seroprotective level (a titer >1/40) was high and similar in both groups. There was no correlation between the response rate and age, gender, or selected parameters of disease activity (tender/swollen joint counts, Leeds enthesitis index, physician and patient global assessment, psoriasis area severity index, and C-reactive protein). No disease exacerbation was observed following the vaccination. No serious adverse effects were observed in both groups during the study period. Secukinumab treatment does not affect the humoral response to influenza vaccine of patients with PsA. [ABSTRACT FROM AUTHOR]

Introduction: This study evaluates a large cohort of college students after the 2009-2010 pandemic H1N1 influenza season. The objective was to assess influenza vaccination status, influenzalike illnesses (ILIs), and other characteristics associated with attaining immunizations.Methods: This study was conducted during the summer 2010 the Reserve Officer Training Corps Leadership Development and Assessment Course involving 6272 college students. A voluntary, anonymous questionnaire was administered to assess study objectives.Results: Vaccination rates were 39.9% for pandemic H1N1, 40.6% for seasonal influenza, and 32.6% for receiving both vaccinations. Age less than 25 and having a Reserve Officer Training Corps scholarship were associated with lower odds of receiving vaccinations, whereas entering the nursing field and simultaneous membership in the Army reserve forces were associated with higher odds of vaccination. There are 11.2% of respondents reported having an ILI, including 4.3% with severe ILI. There were 4184 reasons indicated for not attaining influenza vaccinations, which are listed in categorical groupings.Conclusions: A historical anchor for vaccination rates and ILI is provided in a large cohort of college students following the 2009 H1N1 influenza pandemic. Influenza immunization locations were determined, as was self-reported obstacles to receiving vaccinations. These are important results for public health leaders seeking to increase vaccination rates during future influenza seasons. [ABSTRACT FROM AUTHOR]

Ataxia-telangiectasia (A-T), caused by mutations in the A-T mutated (ATM) gene, is a neurodegenerative disorder affecting ~1 in 40,000 -100,000 children. Recurrent respiratory infections are a common and challenging comorbidity, often leading to the development of bronchiectasis in individuals with A-T. The role of ATM in development of immune memory in response to recurrent respiratory viral infections is not well understood. Here, we infect wild-type (WT) and Atm-null mice with influenza A virus (IAV; HKx31, H3N2) and interrogate the immune memory with secondary infections designed to challenge the B cell memory response with homologous infection (HKx31) and the T cell memory response with heterologous infection (PR8, H1N1). Although Atm-null mice survived primary and secondary infections, they lost more weight than WT mice during secondary infections. This enhanced morbidity to secondary infections was not attributed to failure to effectively clear virus during the primary IAV infection. Instead, Atm-null mice developed persistent peribronchial inflammation, characterized in part by clusters of B220+ B cells. Additionally, levels of select serum antibodies to hemagglutinin-specific IAV were significantly lower in Atm-null than WT mice. These findings reveal that Atm is required to mount a proper memory response to a primary IAV infection, implying that vaccination of children with A-T by itself may not be sufficiently protective against respiratory viral infections. [ABSTRACT FROM AUTHOR]

Introduction: In confined afloat settings, the threat of an acceleration of the Influenza outbreak is substantial, causing high morbidity of the personnel on board, disrupting daily activities, and leading to low crew morale. In this study, H1N1 Influenza outbreak in a Naval Warship and its control measures are described. Materials and Methods: It is a study of 21 clinically suspected cases of H1N1 Influenza. Cases were reported within 3 weeks from a ship company, all of whom were susceptible. They have been described on the basis of demography, clinical features, recent travel history, and history of contact. Results: Mean age of the clinically suspected cases was 26.71 years. Of 21 suspected cases, 14 were found positive for the disease. Nine cases were admitted to the hospital and two developed complications. Attack rate of the disease was 4.83%. Conclusion: In confined afloat settings, prompt public health measures of active case finding, strict isolation, and adherence to hand hygiene, following cough etiquettes and disinfection enhancement, can effectively mitigate the outbreak. Vaccination may not have a role to play if preventive measures are instituted effectively.

Respiratory infections like influenza infections have been found to increase the risk of coronary artery disease and precipitate cardiac failure. However, Indian data is lacking. A retrospective observational study was done to describe patients with influenza infection who had concomitant heart failure (HF) requiring admission over 5 years (January 2013-December 2017). A total of 93 influenza cases were hospitalised during this time, of which 14 (15%) also had features of HF. Among them, the types of influenza infection were AH1N1 (6,43%), BH1N1 (4,29%), AH3N2 (3,21%) with one patient having both strains. Two-thirds of the HF were new onset (10, 71%), whereas rest were due to acute worsening of pre-existing HF (4, 29%). Ten (64.3%) of the patients had HF with reduced ejection fraction (HFrEF). The average hospital stay was 10 days with 2 (14%) deaths. The peak of influenza in August and September preceded the peak admission for HF. A total of 15% of influenza admissions have concomitant HF. They are predominantly due to influenza A H1N1 (43%), influenza A H3N2 (21%) and influenza B (29%). Only 7% had preceding influenza vaccination. Influenza during August and September appears to precede the peak of HF admissions which happen in October and November. Overall mortality was 14% [ABSTRACT FROM AUTHOR]

Various serosurveys and studies were conducted globally on pandemic influenza. H1N1 virus reported so far provides ample evidence of differing perspectives, regarding its epidemiology especially with regard to prevalence, populations groups, and behaviour related to vaccine acceptance. A multigroup, cross-sectional survey among 658 healthy subjects was carried out, in Pune among students, health-care workers (HCWs), and soldiers to assess the seroprevalence of pandemic influenza H1N1 virus and its associated factors. The total sample size, based on forecasted prevalence of 33%, worked out to be 640. We studied 658 subjects including 103 students, 201 HCWs, and 354 serving soldiers. The sample for each group was selected from the respective study population by simple random sampling using a random number table. Haemagglutination inhibition test was carried out at the National Institute of Virology. The overall seroprevalence of pandemic influenza H1N1 (2009) virus was found to be 46.5% (95% confidence interval 42.6–50.4) which was adjusted to 39.4% after excluding those vaccinated. The availability of vaccine for high-risk group such as HCWs did not find much favour with the HCWs who did not accept vaccine for various reasons. Whereas only one student was vaccinated, 21.4% of HCWs and 32.5% of soldiers were vaccinated. Based on high seroprevalence of antibodies against H1N1 virus during pandemic, vaccination of general population is not recommended. However, high-risk groups and HCWs need to be protected with flu vaccine. There is a need to encourage HCWs for accepting vaccination. [ABSTRACT FROM AUTHOR]

Background Prior influenza immunity influences the homologous neutralizing antibody responses elicited by inactivated influenza vaccines (IIV), but neutralizing antibody responses to heterologous strains have not been extensively characterized. Methods We analyzed neutralizing antibody titers in individuals aged 1–88 who received the 2009–2010 season IIV before infection by or vaccination against the 2009 pandemic H1N1 virus. Neutralization titers to homologous and heterologous past, recent, and advanced H1 and H3 strains, as well as H2, H5, and H7 strains, were measured using influenza hemagglutinin pseudoviruses. We performed exploratory analyses based on age, prior-year IIV, and prevaccination titer, without controlling for Type I errors. Results IIV elicited neutralizing antibodies to past and advanced H1 and H3 strains, as well as to an H2 strain in individuals who were likely infected early in life. The neutralization of avian subtype viruses was rare, and there was no imprinting of neutralization responses to novel avian subtype viruses based on the influenza group. Compared to adults, children had higher seroresponse rates to homologous and heterologous strains, and their sera generated larger antigenic distances among strains. Seroresponse rates to homologous and heterologous strains were lower in subjects vaccinated with prior-year IIV, though postimmunization titers were generally high. Conclusions IIV elicited neutralizing antibodies to heterologous H1 and H3 strains in all ages groups, but titers and seroresponse rates were usually higher in children. Prior-year vaccination with the same strains tended to blunt IIV neutralization responses to all strains in young and old age groups, yet postimmunization titers were high. [ABSTRACT FROM AUTHOR]

Background In 2009, a novel influenza A (pH1N1) was identified, resulting in a pandemic with significant morbidity and mortality. A monovalent pH1N1 vaccine was separately produced in addition to the seasonal trivalent influenza vaccine. Formulation of the seasonal influenza vaccine (injectable trivalent inactivated influenza vaccine [TIV] vs. intranasal live, attenuated influenza vaccine [LAIV]) was postulated to have impacted the efficacy of the pH1N1 vaccination. Methods We reviewed electronic health and databases, which included vaccination records, and healthcare encounters for influenza-like illness (ILI), influenza, and pneumonia among US military members. We examined rates by vaccination type to identify factors associated with the risk for study outcomes. Results Compared with those receiving the seasonal influenza vaccine alone, subjects receiving the pH1N1 vaccine, either alone (RR, 0.49) or in addition to the seasonal vaccine (RR, 0.51), had an approximately 50% reduction in ILI, 88% reduction in influenza (RR, 0.11 and 0.12, respectively), and 63% reduction in pneumonia (RR, 0.37 and 0.35, respectively). There was no clinically significant difference in ILI, influenza, or pneumonia attack rates among those receiving the pH1N1 vaccine with or without presence of the seasonal vaccine. Similarly, there was no clinically relevant difference in pH1N1 effectiveness between seasonal TIV and LAIV recipients. Conclusions During the 2009–2010 pandemic, the pH1N1 vaccination was effective in reducing rates of ILI, influenza, and pneumonia. Administration of the seasonal vaccine should continue without concern of potential interference with a novel pandemic vaccine, though more studies are needed to determine if this is applicable to other influenza seasons. [ABSTRACT FROM AUTHOR]

Abstract Background Antenatal influenza vaccination (AIV) is an effective intervention for protecting pregnant women and their newborns against influenza. Although the World Health Organization recommends AIV at any stage of pregnancy, in low- and middle-income countries, including India, it is rarely provided. Research suggests that antenatal care (ANC) provider practices explain much of this limited coverage. Our study in urban Pune, India, assessed the feasibility of a two-stage clinician-engagement strategy to reduce missed opportunities for AIV in urban private-practice ANC clinics. Methods Clinicians were randomized to intervention and control groups in slum and middle-class study sites. Intervention-group clinicians (active clinicians) were assessed on vaccination-related views and practices, and were presented with authoritative AIV recommendations from global, academic and professional medical organizations. In a second meeting after a community survey, findings concerning vaccination-related views and experiences were explained to active clinicians. Assessments of community vaccination views were not provided to control-group clinicians. Both groups maintained logs of ANC clinic visit vaccination status throughout the 11-month study period to enable identification of missed and taken opportunities for vaccination. Analyses were restricted to visits of women in their third trimester without previous AIV in the current pregnancy. Results Overall, 30 clinicians participated. After first and second interactions, active clinicians in middle-class communities vaccinated at 12.2% and 37.8%, respectively. Middle-class control clinicians vaccinated at <0.2% throughout the study. This difference in AIV taken opportunities between middle-class active and control clinics was statistically significant (p < 0.05) after first and second interactions. In slum-community sites, active clinicians' AIV activity was minimal throughout. Conclusions Our approach for engaging clinicians effectively reduced missed opportunities for AIV in urban middle-class settings of Pune. It may also improve maternal vaccination for other conditions. The absence of any similar effect in slum-based clinics likely reflects critical limitations of vaccine access. [ABSTRACT FROM AUTHOR]

Background: A population‐based pregnancy cohort was established in Norway to study potential effects of exposure to the 2009 influenza pandemic or pandemic vaccination during pregnancy. Objectives: We studied maternal A(H1N1)pdm09‐specific hemagglutination inhibition (HI)‐titer levels and waning in women with influenza‐like illness (ILI) in pregnancy compared to vaccinated women. Moreover, we studied the association between HI‐titers and self‐reported severity and duration of ILI. Methods: HI‐titers against the pandemic virus were measured in maternal blood samples obtained at birth, 3‐9 months after exposure, and linked with information about pregnancy, influenza and vaccination from national registries and a cohort questionnaire. Results: Among 1821 pregnant women included, 43.7% were unvaccinated and 19.3% of these had ILI. HI‐titers were low (geometric mean titer (GMT) 11.3) in the unvaccinated women with ILI. Higher HI‐titers (GMT 37.8) were measured in the vaccinated women. Estimated HI‐titer waning was similar for vaccinated women and women with ILI. Most ILI episodes were moderate and lasted 3‐5 days. Women with ILI reporting specific influenza symptoms such as fever or cough had higher HI‐titers than women without these symptoms. Women who reported being "very ill" or illness duration of >5 days had higher HI‐titers than women reporting less severe illness or illness of shorter duration, respectively. Conclusions: Antibody waning was similar in vaccinated women and women with ILI. More severe ILI or longer duration of illness was associated with higher HI‐titers. Most unvaccinated pregnant women with ILI had low HI‐titers, probably due to moderate illness and HI‐titer waning between exposure and sampling. [ABSTRACT FROM AUTHOR]

Background: Although ferret antisera used in influenza surveillance did not detect antigenic drift of A(H1N1)pdm09 viruses during the 2015-2016 season, low vaccine effectiveness was reported in adults. We investigated the immune basis of low responses to circulating A(H1N1)pdm09 viruses after vaccination.Methods: Prevaccination and postvaccination serum samples collected from >300 adults (aged 18-49 years) in 6 seasons (2010-2011 to 2015-2016) were analyzed using hemagglutination inhibition assays to evaluate the antibody responses to 13 A(H1N1) viruses circulated from 1977 to 2016. Microneutralization and serum adsorption assays were used to verify the 163K and 223R specificity of antibodies.Results: Individual antibody profiles to A(H1N1) viruses revealed 3 priming patterns: USSR/77, TW/86, or NC/99 priming. More than 20% of adults had reduced titers to cell-propagated circulating 6B.1 and 6B.2 A(H1N1)pdm09 viruses compared with the A/California/07/2009 vaccine virus X-179A. Significantly reduced antibody reactivity to circulating viruses bearing K163Q was observed only in the USSR/77-primed cohort, whereas significantly lower reactivity caused by egg-adapted Q223R change was detected across all 3 cohorts.Conclusion: Both 163K specificity driven by immune priming and 223R specificity from egg-adapted changes in the vaccine contributed to low responses to circulating A(H1N1)pdm09 viruses after vaccination. Our study highlights the need to incorporate human serology in influenza surveillance and vaccine strain selection. [ABSTRACT FROM AUTHOR]

Objective To assess the possible effect of therapy, disease subtype and severity on H1N1 immunogenicity in patients with SSc. Methods Ninety-two patients and 92 age- and gender-matched healthy controls received adjuvant-free influenza A/California/7/2009 (pH1N1) vaccine. Blood samples were collected immediately before and 3 weeks after vaccination to evaluate antibody responses to the H1N1 virus. Efficacy was assessed by seroprotection (SP) and seroconversion (SC) rates and the factor increase in geometric mean antibody titre. Participants received a 21-day symptom diary card and were instructed to report local and systemic adverse events. Results SSc patients were predominantly females (91%) and 61% had limited SSc, 12% had severe skin involvement and 57.6% were on immunosuppressive (IS) therapy. SSc patients and controls presented comparable overall SP (P = 0.20) and SC (P = 0.61) rates. Further evaluation of the possible effect of disease and therapy revealed similar rates of SP and SC in patients with dcSSc vs lcSSc (SP P = 0.62 and SC P = 0.66), severe vs mild/moderate skin involvement (SP P = 1 and SC P = 0.45) and with vs without IS (SP P = 0.26 and SC P = 0.10). The frequency of mild local and minor systemic reactions was similar in patients with dcSSC vs lcSSc (P = 0.70 vs 0.32) and in those with and without severe skin involvement (P = 0.59 vs 0.28). Conclusion The non-adjuvanted influenza H1N1 virus vaccine proved to be safe and effective, independent of SSc clinical subtype, disease severity or therapy. These latter factors do not seem to contribute to mild adverse events observed in SSc. Our data support the annual influenza vaccination recommendation for these patients. Trial registration ClinicalTrials.gov (http://clinicaltrials.gov), NCT01151644 [ABSTRACT FROM AUTHOR]

Objective: Cross-sectional studies show a lower health-related quality of life (HRQoL) in individuals with narcolepsy. We aimed to describe changes in HRQoL after two years of multidisciplinary follow-up in a cohort of mainly post-H1N1 vaccination narcolepsy type-1 (NT1) patients in Norway.Methods: Prospective-cohort study. Narcolepsy diagnosis was based on the International Classification of Sleep Disorders (third edition). Psychiatric comorbidity was assessed using the Achenbach System of Empirically Based Assessment (ASEBA). HRQoL was evaluated with the Pediatric Quality of Life Inventory (PedsQL™ Generic Core Scales 4.0) at baseline and follow-up. Mean follow-up time was 20.7 (2.7) months.Results: Thirty one patients (18 females) with NT1, mean age 14.6 (SD = 4.8) years answered questionnaires at baseline and follow-up. On a group level, the PedsQL Total Health Summary score significantly improved by a mean of 5.9 (95%CI = 0.4, 11.9), p = 0.038; this was mainly driven by improvements in the Physical Health Summary score by 9.8 (3.0, 16.5) points, p = 0.006 and the School Functioning Scale score by 7.5 (1.0, 13.9) points p = 0.025. The Total ASEBA score was correlated with PedsQL Total Health Summary score at baseline, but not with changes in HRQoL. Sodium oxybate (Xyrem®) treatment at follow up was positively associated with changes in PedsQL Total Health Summary score, after adjusting for age and gender, p = 0.027.Conclusion: HRQoL in NT1 patients improved after two years of follow-up. The use of sodium oxybate (Xyrem®) at follow-up was associated with increases in HRQoL. Psychiatric comorbidity was correlated with HRQoL at baseline but did not predict changes in HRQoL at follow-up. [ABSTRACT FROM AUTHOR]

This report describes 4 narcolepsy cases that were developed after Influenza A/H1N1 infection or vaccination. The durations from Influenza A/H1N1 infection or vaccination to the symptom onset were 10 days, 2 weeks, 3 months, 6 months respectively. Among the four, two were teenagers or younger. One of them developed symptoms after Influenza A/H1N1 infection while three of them developed after vaccination. All went through polysomnography followed by multiple sleep latency tests for accurate diagnosis. All suffered from cataplexy. However, one of them presented with negative results in the human leukocyte antigen DQB1*0602 study. These cases suggest a possibility an association between H1N1/Influenza A virus and narcolepsy development via immune mechanism.

Rapid medical countermeasure (MCM) dispensing is an important intervention during a public health emergency. In the United States, MCM planning and exercising efforts have largely focused on dispensing therapeutics, with less emphasis on mass vaccination operations that would require additional specialized staff and infrastructure. Difficulties in distributing vaccines during the 2009 H1N1 influenza pandemic highlighted the need for enhanced planning and exercising of plans for conducting mass vaccination campaigns. In Taiwan, seasonal influenza mass vaccination campaigns are conducted annually, which both mitigate the effects of seasonal influenza and serve as functional exercises for mass vaccination operations during a pandemic. To identify lessons that can be applied to mass vaccination planning in the United States and elsewhere, we conducted an in-person observation and data review of Taiwan's annual seasonal influenza mass vaccination efforts in October 2017. We offer findings and recommendations for enhancing preparedness for seasonal and pandemic influenza and other public health emergencies that would require mass vaccination. [ABSTRACT FROM AUTHOR]

H1N1, one of the most prevalent influenza A virus subtypes affecting the human population, can cause infections varying from mild respiratory syndrome to severe pneumonia. The current H1N1 vaccine needs to be updated annually and does not protect against future outbreaks. Here, we downloaded 2,656 HA protein sequences of human H1N1 viruses from the NCBI influenza database (up to the date of Aug. 2012) and constructed a phylogenetic tree of these H1 proteins via the neighbor-joining method using MEGA 5.0 software. A consensus H1 protein (CH1) was generated and was further modified with published conserved T-cell and B-cell epitopes. Interestingly, this CH1 protein is genetically similar to an H1 isolate obtained during the 1980s (A/Memphis/7/1980), indicating that a universal HA antigen may exist in nature. Vaccination with a DNA vaccine expressing CH1 elicited broadly reactive T-cell and B-cell responses to heterologous H1N1 viruses, though this vaccine did not successfully neutralize pdm09 H1N1 viruses. A combination of CH1 and pdm09 HA in a DNA vaccination neutralized pdm09 H1N1 viruses and protected mice from lethal infections by all representative H1N1 viruses. Moreover, a recombinant chimeric PR8-CH1 virus carrying HA sequence of the consensus H1 and all other seven genes from the PR8 strain was highly attenuated in mice, with a lethal dose (LD 50 ) of more than 10 6 pfu. Vaccination with PR8-CH1 virus provided complete protection against infections by heterologous H1N1 strains. Taken together, a universal H1 antigen, CH1, was developed by constructing a consensus HA sequence, and the PR8-CH1 virus containing this consensus sequence elicited broadly protective immunity against heterologous H1N1 viruses. [ABSTRACT FROM AUTHOR]

To investigate a potential risk for multiple sclerosis (MS) after vaccination with Arepanrix, the GlaxoSmithKline AS03-adjuvanted influenza A(H1N1)pdm09 vaccine, we used the provincewide immunization registry for Manitoba, Canada, to match 341,347 persons vaccinated during the 2009 pandemic to 485,941 unvaccinated persons on age, sex, address, and a propensity score measuring the probability of vaccination. We used a previously validated algorithm to identify MS cases from provincial hospital, physician, and prescription drug claims databases. After 12 months of follow-up, the age-adjusted incidence rate of MS was 17.7 cases per 100,000 person-years in the Arepanrix cohort and 24.2 per 100,000 in the unvaccinated cohort. The corresponding adjusted hazard ratio was 0.9. We observed similar patterns when we measured incidence over the entire follow-up period. The AS03 adjuvant, a candidate for inclusion in future pandemic vaccines, does not appear to increase the short-term risk for MS when included in influenza vaccines. [ABSTRACT FROM AUTHOR]

Previous research suggests Hispanic vaccination rates for H1N1 were similar to non-Hispanic whites. These previous estimates do not take into account nativity status. Using the 2010 National Health Interview Survey, we estimate adult H1N1 vaccination rates for non-Hispanic whites (n = 8780), U.S.-born Hispanics (n = 1142), and foreign-born Hispanics (n = 1912). To test Fundamental Cause Theory, we estimate odds of H1N1 vaccination while controlling for flexible resources (e.g., educational and economic capital), ethnicity, and nativity status. Foreign-born Hispanics experienced the lowest rates of H1N1 vaccination (15%), followed by U.S.-born Hispanics (18%) and non-Hispanic whites (21%). Regression models show odds of H1N1 vaccination did not differ among these three groups after controlling for sociodemographic characteristics. Insufficient access to flexible resources and healthcare coverage among foreign-born Hispanics was responsible for relatively low rates of H1N1 vaccination. Addressing resource disparities among Hispanics could increase vaccination uptake in the future, reducing inequities in disease burden. [ABSTRACT FROM AUTHOR]