A computer simulation of vaccine prioritization,allocation, and rationing during the 2009 H1N1 influenza pandemic

In the fall 2009, the University of Pittsburgh Models of Infectious Disease Agent Study (MIDAS) team employed an agent-based computer simulation model (ABM) of the greater Washington, DC, metropolitan region to assist the Office of the Assistant Secretary of Public Preparedness and Response, Department of Health and Human Services, to address several key questions regarding vaccine allocation during the 2009 H1N1 influenza pandemic, including comparing a vaccinating children (i.e., highest transmitters)—first policy versus the Advisory Committee on Immunization Practices (ACIP)—recommended vaccinating at-risk individuals-first policy. Our study supported adherence to the ACIP (instead of a children-first policy) prioritization recommendations for the H1N1 influenza vaccine when vaccine is in limited supply and that within the ACIP groups, children should receive highest priority.     

Safety and immunogenicity of whole-virus,alum-adjuvanted whole-virus,virosomal, and whole-virus intradermal influenza A/H9N2 vaccine formulations

Avian influenza H9N2 viruses are considered as a pandemic threat. We assessed the safety and immunogenicity of fourteen H9N2 vaccine formulations. A randomized, phase I trial was done in 353 adults, aged 18–82 years. Subjects received two doses of A/Hong Kong/1073/99 (H9N2) whole-virus, alum-adjuvanted whole-virus, virosomal, or intradermal whole-virus vaccine at four doses (1.7, 5, 15 or 45 μg haemagglutinin). Sera were obtained before and three weeks after each vaccination (days 0, 21, and 42) for haemagglutination–inhibition (HAI) and neutralization assays. All formulations were well tolerated. Pre-vaccination sera from subjects aged below or above 40 years had baseline antibody to H9N2 in 1% and 16% of samples. Compared to intramuscular whole-virus vaccine, alum-adjuvanted vaccine was more immunogenic, intradermal vaccine was comparable, and virosomal vaccine less immunogenic. Among subjects under 40 years, two doses (45, 15, and 5 μg) of alum-adjuvanted vaccine achieved seroprotective HAI titres in 50%, 41%, and 39% respectively, and neutralization seroconversions in 83%, 82%, and 78% of recipients. Among subjects over 40 years, one dose (45, 15, and 5 μg) of alum-adjuvanted vaccine achieved seroprotective HAI titres in 50%, 25% and 0% respectively, and neutralization seroconversions in 88%, 63% and 63% of recipients. Among immunologically naive subjects under 40 years, two doses of vaccine are required and alum-adjuvanted vaccines were most immunogenic. Among immunologically primed subjects over 40 years, one dose of whole-virus or alum-adjuvanted vaccine induced immune responses; the second dose provided less additional benefit. However, no vaccine formulation satisfied all European regulatory criteria for pandemic vaccines.     

Extensive Mammalian Ancestry of Pandemic (H1N1) 2009 Virus

We demonstrate that the novel pandemic influenza (H1N1) viruses have human virus–like receptor specificity and can no longer replicate in aquatic waterfowl, their historic natural reservoir. The biological properties of these viruses are consistent with those of their phylogenetic progenitors, indicating longstanding adaptation to mammals.     

The influence of the multi-basic cleavage site of the H5 hemagglutinin on the attenuation, immunogenicity and efficacy of a live attenuated influenza A H5N1 cold-adapted vaccine virus

A recombinant live attenuated influenza virus ΔH5N1 vaccine with a modified hemagglutinin (HA) and intact neuraminidase genes from A/Vietnam/1203/04 (H5N1) and six remaining genome segments from A/Ann Arbor/6/60 (H2N2) cold-adapted (AA ca) virus was previously shown to be attenuated in chickens, mice and ferrets. Evaluation of the recombinant H5N1 viruses in mice indicated that three independent factors contributed to the attenuation of the ΔH5N1 vaccine: the attenuating mutations specified by the AA ca loci had the greatest influence, followed by the deletion of the H5 HA multi-basic cleavage site (MBS), and the constellation effects of the AA genes acting in concert with the H5N1 glycoproteins. Restoring the MBS in the H5 HA of the vaccine virus improved its immunogenicity and efficacy, likely as a consequence of increased virus replication, indicating that removal of the MBS had a deleterious effect on the immunogenicity and efficacy of the ΔH5N1 vaccine in mice.     

墨西哥甲型H1N1流感防控策略及其经验

墨西哥是最早出现甲型H1N1流感疫情的国家,面对疫情的诸多不确定因素,墨西哥政府在出现甲型H1N1流感疫情后依据《国家流感大流行应急准备计划》,发布了全国范围内的流感流行预警,宣布进入卫生紧急状态,同时积极开展广泛的国际交流与合作,采取了关闭学校、取消集会、停止商业活动等一系列非药物干预措施,这对于遏制、消灭甲型H1N1流感大流行发挥了重要的积极作用,也提供了较好的国际经验。本文在对墨西哥甲型H1N1流感防控调研的基础上,对其疫情各阶段采取的主要防控措施进行梳理,并对其经验和不足进行总结,以期为我国今后有效应对流感大流行提供宝贵的可借鉴的经验。     

Which factors are important in adults’ uptake of a (pre)pandemic influenza vaccine?

Since 2008, (pre)pandemic vaccines against H5N1 influenza have been available and pandemic vaccines against new influenza H1N1 are currently produced. In The Netherlands, the vaccination call for seasonal influenza among the recommended groups approximates 70%. These statistics raise the question if adults in Western societies are willing to get a (pre)pandemic influenza vaccination, for example, against avian H5N1 or swine-like H1N1 virus. A questionnaire was performed to determine the predictors of a negative intention to be immunized against pandemic influenza among adults. Demographical, behavioural and organisational determinants were studied. Thirty-four and five percent of the respondents were negatively intended to get a pandemic influenza vaccination in a pre-pandemic or pandemic phase, respectively. On the basis of six behavioural determinants negative intention to get a pandemic influenza vaccination can be predicted correctly in almost 80% of the target group. These determinants should be targeted in pandemic preparedness plans.     

Willingness of healthcare workers to accept voluntary stockpiled H5N1 vaccine in advance of pandemic activity

Healthcare workers may be at risk during the next influenza pandemic. Priming with stockpiled vaccine may protect staff and reduce nosocomial transmission. Despite campaigns to increase seasonal influenza vaccine coverage, uptake among healthcare workers is generally low; creating uncertainty whether they would participate in pre-pandemic vaccine programmes. We conducted a cross-sectional questionnaire survey of healthcare workers in a UK hospital during, and 6 months after, a period of media reporting of an H5N1 outbreak at a commercial UK poultry farm. A total of 520 questionnaires were returned, representing 20% of frontline workforce. More respondents indicated willingness to accept stockpiled H5N1 vaccine during the period of media attention than after (166/262, 63.4% vs. 134/258, 51.9%; p = 0.009). Following multivariate analysis, factors associated with willingness to accept H5N1 vaccine included: previous seasonal vaccine (OR 6.2, 95% CI 3.0–12.8, p < 0.0001), awareness of occupational seasonal vaccine campaigns (OR 2.2, 95% CI 1.4–3.5, p = 0.001), belief that seasonal vaccine benefits themselves (OR 2.5, 95% CI 1.6–4.0, p < 0.0001) or the hospital (OR 3.6, 95% CI 2.3–5.8, p < 0.0001), belief that pandemic risk is high/moderate (OR 14.1, 95% CI 7.6–26.1, p < 0.0001) and would threaten healthcare workers (OR 2.9, 95% CI 1.8–4.5, p < 0.0001). Those who would not accept vaccine (220 respondents, 42.7%) if offered before the pandemic do not perceive pandemic influenza as a serious threat, and have concerns regarding vaccine safety. A majority of healthcare workers are amenable to accept stockpiled H5N1 vaccine if offered in advance of pandemic activity.