Effects of Prior Influenza Exposure on Immunogenicity of Influenza Vaccine

Abstract
In this study, we investigated the effects of prior influenza exposure on vaccine-elicited humor immune responses to circulating influenza variants. 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. Subjects with H1-priming had higher cross-reactive antibodies titers against A/JiangsuTinghu/11019/2015(H3N2) compared with subjects with B-priming did (Padjusted = .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 (Padjusted = .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 (Padjusted = .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. 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.