Dataset Information

Effects of Prior Influenza Exposure on Immunogenicity of Influenza Vaccine.

ABSTRACT:

Background

In this study, we investigated the effects of prior influenza exposure on vaccine-elicited humor immune responses to circulating influenza variants.

Method

We randomly selected 360 participants in previous clinical trials stratified by age. Blood samples were collected and tested by hemagglutination-inhibition tests during the 2015-2016 influenza seasons in China. The antigenic map was plotted and antigenic distance was calculated.

Results

Subjects with H1-priming had higher cross-reactive antibodies titers against A/JiangsuTinghu/11019/2015(H3N2) compared with subjects with B-priming did (P _adjusted = .038). Subjects with H1-priming also had higher cross-reactive antibodies titers against A/Jiangsu Qinhuai/11059/2015(H3N2) than subjects with both H1 and B priming (P _adjusted = .036). Nevertheless, subjects with no H1 and B-priming had higher cross-reactive antibodies titers against A/Jiangsu Qinhuai/11059/2015(H3N2) than subjects with both H1 and B priming (P _adjusted = .012). Antigenic distance was well matched with serological results. Moeover, age-specific differences in human postvaccination responses against the identical circulating strain was noted. In addition, children had the most cross-reactive response to both H3N2 and B-yamagata subtypes.

Conclusions

Our results suggest that prior exposure to H1 or B influenza virus may influence cross-reactivity of H3-specific postvaccination responses and consequently could influence the vaccine effectiveness. Our findings also support that there are age-specific differences in human postvaccination responses.

SUBMITTER: Cao JQ

PROVIDER: S-EPMC7423295 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

Effects of Prior Influenza Exposure on Immunogenicity of Influenza Vaccine.

Cao Jia-Qian JQ Jin Peng-Fei PF Li Jing-Xin JX Zeng Zhao-Zhun ZZ Zhang Li L Meng Fan-Yue FY Chu Kai K Wang Yuan-Yuan YY Zhu Feng-Cai FC

Open forum infectious diseases 20200526 8

<h4>Background</h4>In this study, we investigated the effects of prior influenza exposure on vaccine-elicited humor immune responses to circulating influenza variants.<h4>Method</h4>We randomly selected 360 participants in previous clinical trials stratified by age. Blood samples were collected and tested by hemagglutination-inhibition tests during the 2015-2016 influenza seasons in China. The antigenic map was plotted and antigenic distance was calculated.<h4>Results</h4>Subjects with H1-primin ...[more]

PMID: 32818136

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Project description:BackgroundExisting methods to measure influenza vaccine immunogenicity prohibit detailed analysis of epitope determinants recognized by immunoglobulins. The development of highly multiplex proteomics platforms capable of capturing a high level of antibody binding information will enable researchers and clinicians to generate rapid and meaningful readouts of influenza-specific antibody reactivity.MethodsWe developed influenza hemagglutinin (HA) whole-protein and peptide microarrays and validated that the arrays allow detection of specific antibody reactivity across a broad dynamic range using commercially available antibodies targeted to linear and conformational HA epitopes. We derived serum from blood draws taken from 76 young and elderly subjects immediately before and 28±7 days post-vaccination with the 2008/2009 trivalent influenza vaccine and determined the antibody reactivity of these sera to influenza array antigens.ResultsUsing linear regression and correcting for multiple hypothesis testing by the Benjamini and Hochberg method of permutations over 1000 resamplings, we identified antibody reactivity to influenza whole-protein and peptide array features that correlated significantly with age, H1N1, and B-strain post-vaccine titer as assessed through a standard microneutralization assay (p<0.05, q <0.2). Notably, we identified several peptide epitopes that were inversely correlated with regard to age and seasonal H1N1 and B-strain neutralization titer (p<0.05, q <0.2), implicating reactivity to these epitopes in age-related defects in response to H1N1 influenza. We also employed multivariate linear regression with cross-validation to build models based on age and pre-vaccine peptide reactivity that predicted vaccine-induced neutralization of seasonal H1N1 and H3N2 influenza strains with a high level of accuracy (84.7% and 74.0%, respectively).ConclusionOur methods provide powerful tools for rapid and accurate measurement of broad antibody-based immune responses to influenza, and may be useful in measuring response to other vaccines and infectious agents.

Project description:In young children, infrequent antigen exposure, which is partly characterized by fewer vaccinations, may be a factor impairing the immunogenicity of inactivated influenza vaccine.We assessed the effects of prior vaccinations on age-specific immune responses in Japanese children aged 6 months to 3 years, using data from a cohort study with 266 children who had received 2 doses (0.25?mL/dose for < 3 years old, 0.5?mL/dose for 3 years old) in the 2006/2007 season. Serological measures, primarily seroprotection rates, between previously vaccinated and vaccine-naïve children were compared within 1-year age strata. The seroprotection rate was defined in 2 ways as the proportion of subjects who achieved an antibody titer of 1:40 or 1:160. Multivariate logistic regression was also performed to estimate the independent effect of prior vaccination on seroprotection rate.After the first dose, seroprotection rates with the threshold of 1:40 in vaccine-naïve 1-year-olds remained low (28% for AH1, 26% for AH3, 2% for B), similar to those of 0-year-olds. In contrast, seroprotection rates in previously vaccinated 1-year-olds (77% for AH1, 86% for AH3, 18% for B) were significantly higher than those in vaccine-naïve 1-year-olds. These seroprotection rates for AH1 and AH3 were comparable with those in previously vaccinated 2- and 3-year-olds. Although seroprotection rates for B remained low in every age stratum even after the second dose, seroprotection rate in previously vaccinated 1-year-olds (50%) was similar to that in 3-year-olds. After adjustment for age, baseline antibody titer and experience of acute febrile respiratory illness in the preceding season, odds ratios showed a significant independent positive effect of prior vaccination on seroprotection rate for every strain. After the seroprotection threshold was changed from 1:40 to 1:160, the results of the effects of prior vaccinations on immunogenicity were similar or became more evident, which demonstrate the robustness of our findings.Our study found that prior vaccinations improved poor immunogenicity among young children, especially in 1-year-olds.

Dataset Information

Effects of Prior Influenza Exposure on Immunogenicity of Influenza Vaccine.

Background

Method

Results

Conclusions

Publications

Effects of Prior Influenza Exposure on Immunogenicity of Influenza Vaccine.

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