Effects Of Prior Influenza Exposure On Immunogenically Responses To Influenza Vaccine

【Objective】The effectiveness of seasonal flu vaccines varies greatly in different flu seasons.Although influenza vaccine strains are evaluated and updated annually by the World Health Organization（WHO）,the vaccine effect is sometimes unavoidably unsatisfactory.Many factors may contribute to it.Our study was designed to investigate the effects of prior influenza exposure on the vaccine-elicited humor immune responses to the circulating influenza variants,and to improve the effectiveness of influenza vaccines and provide a scientific basis for influenza vaccination.【Methods】From January 2016 to August 2016,a randomized,parallel-controlled,double-blind,non-inferiority Phase III clinical trial of a novel QIV was conducted in Lianyungang City,Jiangsu province,China.We randomly selected 720 participants in this clinical trials stratified by age,including 120 children（3-17 years）,120 adults（18-59 years）and 120 elderly people（≥60 years）in the experimental QIV group,60children（3-17 years）,60 adults（18-59 years）and 60 elderly people（≥60 years）in the TIV-Victoria group,and 60 children（3-17 years）,60 adults（18-59 years）and 60elderly people（≥60 years）in the TIV-Yamagata group.They were vaccinated with one-dose split-virus quadrivalent or trivalent influenza vaccines in 2015 winter.Blood samples before and 28 days after the vaccination were collected,and tested by using hemagglutination inhibition tests against both the vaccine strains and the irculating influenza variants during the 2015–2016 influenza seasons,in Jiangsu Province,China.The antigen map was plotted and the antigen distance was alculated.The previous exposure was defined as seroprotective HAI titer of≥40before vaccination.Geometric mean titers and Geometric mean titers ratio was aucalated,Kruskal-Wallis rank sum test was used to compare the difference of GMT ratio across the different exposure groups and age groups.【Results】1.In the experimental group,subjects with H1-priming had higher cross-reactive antibodies titers against A/Jiangsu Tinghu/11019/2015（H3N2）compared with subjects with B-priming did(P_adjusted=0.038).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 did(P_adjusted=0.036).While,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 did(P_adjusted==0.012).2.In the control group 2,subjects with H1-priming had higher cross-reactive antibodies titers against A/Jiangsu Tinghu/11925/2016（H3N2）compared with subjects with B-priming did(P_adjusted=0.025).3.Antigenic distance was well-matched with serological results.Besides,age-specific differences in human post-vaccination responses against the identical circulating strain was noted.4.In the experimental group,children had higher cross-reactive antibodies titers against A/Jiangsu Tinghu/SWL144/2016（H1N1）compared with adults did(P_adjusted=0.038),but adults had higher cross-reactive antibodies titers against A/Jiangsu Gaoyou/SWL1118/2016（H1N1）compared with children did(P_adjusted=0.007).Both children(P_adjusted<0.001)and adults(P_adjusted=0.01)had higher cross-reactive antibodies titers against A/Jiangsu Tinghu/11019/2015（H3N2）than the elderly did,so did in B/Jiangsu Tianning/16/2016（BY）(P_adjusted=0.001and P_adjusted=0.002,respectively).Moreover,Children had higher cross-reactive antibodies titers against B/Jiangsu Nanjing Gulou/16/2016（BY）than the elderly did(P_adjusted=0.033).5.In the control group 1,the elderly had higher cross-reactive antibodies titers against A/Jiangsu Qinhuai/11059/2015（H3N2）than children(P_adjusted<0.001)and adults(P_adjusted=0.003)did.Children had higher cross-reactive antibodies titers against A/Jiangsu Tinghu/11019/2015（H3N2）than the elderly did(P_adjusted=0.027).6.In the control group 2,Both children(P_adjusted=0.022)and the elderly(P_adjusted=0.001)had higher cross-reactive antibodies titers against A/Jiangsu Quanshan/SWL124/2016（H1N1）than adults did.Both children(P_adjusted<0.001)and adults(P_adjusted=0.001)had higher cross-reactive antibodies titers against A/Jiangsu Qinhuai/11059/2015（H3N2）than the elderly did.In addition,children had higher cross-reactive antibodies titers against A/Jiangsu Haizhou/19/2016（H3N2）than adults did(P_adjusted<0.001).【Conclusions】Our results suggest that prior exposure to H1 or B influenza virus may influence cross-reactivity of H3-specific postvaccination responses and onsequently could influence the vaccine effectiveness.Our findings also support that there are age-specific differences in human postvaccination responses.