Safety and immunogenicity of 2010-2011 H1N12009-containing trivalent inactivated influenza vaccine in children 12-59 months of age previously given AS03-adjuvanted H1N12009 pandemic vaccine: a PHAC/CIHR Influenza Research Network (PCIRN) study

Background

Concern arose in 2010 that reactogenicity, particularly febrile seizures, to influenza A/H1N1-containing 2010–2011 trivalent seasonal inactivated influenza vaccine (TIV) could occur in young children who had been previously immunized and/or infected with the pandemic strain. We conducted a pre-season study of 2010–2011 TIV safety and immunogenicity in children 12–59 months of age to inform public health decision making.

Methods

Children immunized with 1 or 2 doses of the pandemic vaccine, with or without the 2009–10 TIV, received 1 or 2 doses of 2010–11 TIV in an observational, multicentre Canadian study. Standard safety monitoring was enhanced by a telephone call at ∼24 h post-TIV when adverse events were expected to peak. Summary safety reports were rapidly reported to public health before the launch of public programs. TIV immunogenicity was assessed day 0, and 21 days after final vaccination. Clinical Trials Registration NCT01180621.

Results

Among 207 children, a general adverse event was reported by 60.9% of children post-dose one and by 58.3% post-dose two. Only severe fever (>38.5 °C) was more common in two-dose compared to one dose recipients (16.7%, n = 4 v. 1.0%, n = 2). At baseline 99.0% of participants had A/H1N1 hemagglutinin inhibition (HAI) titers ≥10, and 85.5% had a protective titer of ≥40 (95% CI 80.0, 90.0). Baseline geometric mean titers (GMT) were higher in recipients of a 2-dose schedule of pandemic vaccine compared to one-dose recipients: 153.1 (95% CI 126.2, 185.7) v. 78.8 ((58.1, 106.8, p < 0.001). At 21 days, all regulatory criteria for influenza vaccine immunogenicity were exceeded for A/H1N1 and H3N2, but responses to the B antigen were poor. No correlations between reactogenicity and either baseline high influenza titers or serologic response to revaccination were evident.

Conclusions

Infants and toddlers who received AS03-adjuvanted A/H1N1 2009 vaccine up to 11 months earlier retained high titers in the subsequent season but re-exposure to A/H1N1 2009 antigen in TIV resulted in no unusual adverse effects and 100% were sero-protected for A/H1N1 after receipt of the 2010–11 TIV.     

Enhancing the reproducibility of serological methods used to evaluate immunogenicity of pandemic H1N1 influenza vaccines-an effective EU regulatory approach

Haemagglutination-inhibition (HI) and virus neutralisation (VN) assays are routinely applied to evaluate influenza vaccine immunogenicity for regulatory approval. Despite their frequent use both assays are currently only poorly standardised causing considerable inter-laboratory variation of serological results that is particularly evident for pandemic influenza vaccines. The present study was conducted in association with the European Medicines Agency (EMA) to directly compare assay variability between vaccine manufacturer's and European regulatory agency's laboratories in an influenza pandemic scenario. To this end, a defined subset of H1N1 pdm clinical trial sera from all manufacturers that had applied at EMA for approval of pandemic H1N1 vaccines were re-tested by the National Institute for Biological Standards and Control (for HI) and the Paul Ehrlich Institute (for VN). Comparative analysis of test results determined for almost 2000 serum samples revealed a marked inter-laboratory variation for HI titres (up to 5.8-fold) and even more for neutralisation titres (up to 7.0-fold). When the absolute titres were adjusted relative to the calibrated International Antibody Standard 09/194 variation was drastically reduced and acceptable agreement of results from different laboratories could be achieved. Hence, inclusion of an appropriate calibrated antibody standard for adjustment of original titres is a powerful tool to substantially increase reproducibility of serological results from different laboratories and to significantly improve regulatory evaluation of influenza vaccine efficacy.     

Nurses' vaccination against pandemic H1N1 influenza and their knowledge and other factors

This study aimed to estimate the vaccination coverage against the pandemic H1N1 influenza in a group of nurses and determine the factors associated with their vaccination behaviours. An anonymous, self-administered questionnaire was distributed to a convenience sample of nurses who were enrolled on continuing professional education courses in a university in London. The survey response rate was 77.7% (n=522). A total of 172 (35.2%) nurses reported receiving the pandemic H1N1 vaccine in the 2009-2010 influenza season and only 22.3% of them had the intent to accept the vaccine in the next season. Compared to nurses with low knowledge scores, those with high knowledge scores were more likely to receive the pandemic H1N1 vaccine (p=0.017), recommend the vaccine to their patients (p=0.003), and have the willingness to recommend vaccination to patients in the future (p=0.009). There was a higher vaccination rate among nurses with higher risk perception scores than with lower scores (p=0.001). A small, positive correlation between H1N1 knowledge and risk perception scores was identified (p<0.001) indicating that a high knowledge level was associated with high levels of risk perception. More male nurses received the H1N1 vaccine than females (p<0.001) and there were a significant differences in the uptake among nurses from different clinical specialty groups (p<0.001). About half of the vaccinated nurses reported the intent to be vaccinated again but only 8.1% of the unvaccinated nurses had the intent to receive the vaccine in the next season (p<0.001). The pandemic H1N1 2009 influenza vaccination coverage among this nurse sample was sub-optional. Lack of knowledge and risk perception were predictors associated with the nurses' vaccination behaviours. The identified knowledge items should be addressed in future vaccination campaigns. The hindrances associated with continuing vaccination decision-making and factors contributing to the different vaccination coverage among clinical specialty groups require further exploration.     

Vaccine-related standard of care and willingness to respond to public health emergencies: A cross-sectional survey of California vaccine providers

Introduction

Responding to a vaccine-related public health emergency involves a broad spectrum of provider types, some of whom may not routinely administer vaccines including obstetricians, pharmacists and other specialists. These providers may have less experience administering vaccines and thus less confidence or self-efficacy in doing so. Self-efficacy is known to have a significant impact on provider willingness to respond in emergency situations.

Methods

We conducted a survey of 800 California vaccine providers to investigate standard of care, willingness to respond, and how vaccine-related standard of care impacts willingness to respond among these providers. We used linear regression to examine how willingness to respond was impacted by vaccine-related standard of care.

Results

Forty percent of respondents indicated that they had participated in emergency preparedness training, actual disaster response, or surge capacity initiatives with significant differences among provider types for all measures (p = 0.007). When asked to identify barriers to responding to a public health emergency, respondents indicated that staff size or capacity, training and resources were the top concerns. Respondents in practices with a higher vaccine-related standard of care had a higher willing to respond index (β = 0.190, p = 0.001). Respondents who had participated in emergency training or actual emergency response had a higher willing to respond index (β = 1.323, p < 0.0001).

Conclusion

Our study suggests that concerns about staff size and surge capacity need to be more explicitly addressed in current emergency preparedness training efforts. In the context of boosting response willingness, larger practice environments stand to benefit from self-efficacy focused training and exercise efforts that also incorporate standard of care.     

新型禽源人流感病毒（H7N9）的小鼠感染模型和传播模型建立

目的建立新型禽源人流感病毒（H7N9）小鼠模型和可能的H7N9致病性和传播力研究。方法H7N9病毒感染小鼠,并与同居小鼠合笼,研究同居小鼠的临床指征变化,病毒复制情况,病毒在组织中的分布,以及病理变化。通过观察同居小鼠的发病情况等方面研究H7N9病毒在同笼小鼠中的传播能力。结果研究表明H7N9病毒能有效地感染小鼠并造成致死,可以通过直接接触传播感染小鼠并引起病理等改变。结论建立了H7N9小鼠模型,并对小鼠通过接触传播感染进行了初步研究,为深入研究传播力奠定了基础。     

Using automation to manage donor engagement and fine-tune supply and demand during the first year of the COVID-19 pandemic

BackgroundCOVID-19 disrupted blood center operations starting March 2020 and continues to affect donor presentation and blood availability today. The industry mobilized significant resources to collect COVID-19 convalescent plasma (CCP) to treat COVID-19 patients. At the same time, blood centers continued to collect platelets, plasma, and red blood cells (RBCs) to meet the needs of non-COVID-19 patients. The purpose of this study was to quantify how automation was used to fine-tune supply and demand and increase donor engagement during the first year of the pandemic.MethodsThis was a single-center retrospective study of blood collection and donor presentation at a mid-sized US blood center. Data was evaluated from January 1, 2020 through March 31, 2021. Parameters evaluated included donor presentation, platelets per procedure, concurrent RBC and plasma collections per procedure, operator compliance, total donor appointment count, and donor frequency.ResultsWith the cancelation of mobile blood drives, fixed sites increased total apheresis procedures by 37% and increased turns per bed by 46% whereas less products were collected per donor. By collecting only what was needed, platelet expiration rate decreased from 6.8% (pre-pandemic) to less than 4%. Donor engagement as measured by donor frequency increased from 1.6 in January 2020 to 1.8 in March 2021.ConclusionsUsing technological advances such as automated blood collection and information systems, the blood center improved donor engagement and avoided collecting a surplus of any one type of blood product over the course of the pandemic     

Blood shortages and changes to massive transfusion protocols: Survey of hospital practices during the COVID-19 pandemic

IntroductionThe COVID-19 pandemic has resulted in severe ongoing blood shortages across the US, despite employment of numerous blood-conservation measures. Massive transfusion protocols (MTP) are one resource-intensive practice that utilize significant amounts of blood products. Alterations to the composition of MTP parameters to conserve scarce biologic resources have hitherto not been examined during the pandemic.MethodsAn anonymous 18-question survey was administered to 115 hospitals with valid email contact information. Survey questions addressed whether institutions have altered their MTPs due to the COVID-19 pandemic and blood shortages, and if so, what adjustments they have made. Additional details concerning potential differences in the number and cycles of MTPs and blood product wastage during the COVID-19 pandemic compared to the year prior were assessed.Results50 responses were received (43 % response rate). 10 % (5/50) of institutions altered their MTPs utilizing a variety of approaches in attempt to conserve blood during the COVID-19 pandemic. Four additional institutions intend to alter them if it becomes necessary. Following onset of the COVID-19 pandemic, 24 % of institutions (12/50) reported an increase in monthly MTP activations, while 16 % (8/50) reported decreased activations compared to prior to the pandemic. 22 % (11/50) of institutions experienced increased blood wastage, whereas 16 % (8/50) reported decreased waste compared to pre-pandemic.DiscussionThe results of this survey highlight a variety of mechanisms by which institutions have attempted to conserve blood via altering MTPs. Whether an institution adjusted their MTP does not correlate with changes in blood product wastage compared to pre-pandemic.     

Pandemic influenza threat and preparedness

The threat of a human influenza pandemic has greatly increased over the past several years with the emergence of highly virulent avian influenza viruses, notably H5N1 viruses, which have infected humans in several Asian and European countries. Previous influenza pandemics have arrived with little or no warning, but the current widespread circulation of H5N1 viruses among avian populations and their potential for increased transmission to humans and other mammalian species may afford us an unprecedented opportunity to prepare for the next pandemic threat. The US Department of Health and Human Services is coordinating a national strategy to respond to an influenza pandemic that involves multiple agencies, including the Centers for Disease Control and Prevention, the Food and Drug Administration, and the National Institutes of Health (NIH). Within NIH, the National Institute of Allergy and Infectious Diseases (NIAID) conducts basic and clinical research to develop new vaccine technologies and antiviral drugs against influenza viruses. We describe recent research progress in preparing for pandemic influenza.