Effect of Aluminum Hydroxide Adjuvant on the Immunogenicity of the 2009 Pandemic Influenza A/H1N1 Vaccine:Multi-level Modeling of Data with Repeated Measures

Objective To evaluate the effect of the aluminum hydroxide （Al-OH） adjuvant on the 2009 pandemic influenza A/H1N1 （pH1N1） vaccine. Methods In a multicenter, double-blind, randomized, placebo-controlled trial, participants received two doses of split-virion formulation containing 15 ug hemagglutinin antigen, with or without aluminum hydroxide （N-OH）. We classified the participants into six age categories （〉61 years, 41-60 years, 19-40 years, 13-18 years, 8-12 years, and 3-7 years） and obtained four blood samples from each participant on days 0, 21, 35, and 42 following the first dose of immunization. We assessed vaccine immunogenicity by measuring the geometric mean titer （GMT） of hemagglutination inhibiting antibody. We used a two-level model to evaluate the fixed effect of aluminum Al-OH and other factors, accounting for repeated measures. Results The predictions of repeated measurement on GMTs of formulations with or without Al-OH, were 80.35 and 112.72, respectively. Al-OH significantly reduced immunogenicity after controlling for time post immunization, age-group and gender. Conclusion The Al-OH adjuvant does not increase but actually reduces the immunogenicity of the split-virion pH1N1 vaccine.

Comparing the transmission potential from sequence and surveillance data of 2009 North American influenza pandemic waves

Technological advancements in phylodynamic modeling coupled with the accessibility of real-time pathogen genetic data are increasingly important for understanding the infectious disease transmission dynamics.In this study,we compare the transmission potentials of North American influenza A(H1N1)pdm09 derived from sequence data to that derived from surveillance data.The impact of the choice of tree-priors,informative epidemiological priors,and evolutionary parameters on the transmission potential estimation is evaluated.North American Influenza A(H1N1)pdm09 hemagglutinin(HA)gene sequences are analyzed using the coalescent and birth-death tree prior models to estimate the basic reproduction number(R_(0)).Epidemiological priors gathered from published literature are used to simulate the birth-death skyline models.Path-sampling marginal likelihood estimation is conducted to assess model fit.A bibliographic search to gather surveillancebased R_(0)values were consistently lower(mean≤1.2)when estimated by coalescent models than by the birth-death models with informative priors on the duration of infectiousness(mean≥1.3 to≤2.88 days).The user-defined informative priors for use in the birth-death model shift the directionality of epidemiological and evolutionary parameters compared to non-informative estimates.While there was no certain impact of clock rate and tree height on the R_(0)estimation,an opposite relationship was observed between coalescent and birth-death tree priors.There was no significant difference(p=0.46)between the birth-death model and surveillance R0 estimates.This study concludes that treeprior methodological differences may have a substantial impact on the transmission potential estimation as well as the evolutionary parameters.The study also reports a consensus between the sequence-based R_(0)estimation and surveillanceased R_(0)stimates.Altogether,these outcomes shed light on the potential role of phylodynamic modeling to augment existing surveillance and epidemiological activities to better assess and respond to emerging infectious diseases.

Detection and pathogenesis of a novel swine H3N2 influenza virus containing three genes from the 2009 pandemic H1N1 influenza viruses in Korea in 2015

Dear Editor,Influenza A viruses cause pandemics at an interval of approximately 10-40 years,and pigs are regarded as a＂mixing vessel＂because they are easily infected with avian and human influenza viruses（Ito et al.,1998）.According to previous studies,H3N2,H1N2,and H1N1 subtypes o（swine influenza viruses have been detected in Korean pigs （Pascua et al., 2013; Kim et al., 2014; Song et al., 2007）. Moreover, a novel H3N2 influenza virus containing the matrix （34） gene from a 2009 pandemic influenza virus was detected in Korean pigs in 2013 （Pascua et al., 2013）, an H1N2 influenza virus con- taining the internal genes from a 2009 pandemic influ- enza virus was found in Korean pigs in 2014 （Kim et al., 2014）, and an H1N1 influenza virus containing all genes from the classical swine influenza viruses was isolated from Korean pigs in 2007 （Song et al., 2007）.