复旦大学徐建青课题组揭示流感病毒感染后抗体应答新规律
2013年H7N9禽流感病毒出现以来，一直持续威胁人类健康。复旦大学徐建青、张晓燕课题组近日在国际权威学术期刊Journal of Infectious Disease发表题为Inductionof Broadly Cross-Reactive Stalk-Specific Antibody ResponsestoInfluenzaGroup 1 andGroup 2 Hemagglutinins by Natural H7N9 Virus Infection in Humans.的文章，揭示了流感病毒感染后抗体应答新规律。为了更科学设计疫苗，徐建青课题组在国际上首次同步利用涵盖流感两大组的三十多个流感HA膜蛋白，观察H7N9感染者不同时相的抗体应答，发现感染者早期快速升高的以广谱识别流感的抗体为主，H7特异性抗体升高晚于广谱识别抗体；广谱识别流感的抗体以针对流感颈部位点为主，且与中和活性成正比，血凝抑制应答与中和活性相关性不显著。此项研究首次揭示针对流感病毒颈部保守表位免疫应答可通过不同流感先后感染获得快速提升，且早于特异性抗体，这一现象为解释流感领域“抗原原罪（Original Antigen Sin）”（即之前流感感染可干扰后续流感的免疫应答）之谜提供科学依据，也为未来设计广谱抗流感疫苗提供科学依据。
该工作得到国家自然科学基金委员会、上海市申康医院发展中心及美国国立卫生研究院支持。
Induction of Broadly Cross-Reactive Stalk-Specific Antibody Responses to Influenza Group 1 and Group 2 Hemagglutinins by Natural H7N9 Virus Infection in Humans
Abstract
BACKGROUND.:
The outbreak of novel avian H7N9 influenza virus infections in China in 2013 has demonstrated the continuing threat posed by zoonotic pathogens. Deciphering the immune response during natural infection will guide future vaccine development.
METHODS.:
We assessed the induction of heterosubtypic cross-reactive antibodies induced by H7N9 infection against a large panel of recombinant hemagglutinins and neuraminidases by quantitative enzyme-linked immunosorbent assay, and novel chimeric hemagglutinin constructs were used to dissect the anti-stalk or -head humoral immune response.
RESULTS.:
H7N9 infection induced strong antibody responses against divergent H7 hemagglutinins. Interestingly, we also found induction of antibodies against heterosubtypic hemagglutinins from both group 1 and group 2 and a boost in heterosubtypicneutralizing activity in the absence of hemagglutination inhibitory activity. Kinetic monitoring revealed thatheterosubtypic binding /neutralizing antibody responses typically appeared and peaked earlier than intrasubtypic responses, likely mediated by memory recall responses.
CONCLUSIONS.:
Our results indicate that cross-group binding and neutralizing antibody responses primarily targeting the stalk region can be elicited after natural influenza virus infection. These data support our understanding of the breadth of the postinfection immune response that could inform the design of future, broadly protective influenza virus vaccines.
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