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Transbound Emerg Dis
. 2020 Jun 29.
doi: 10.1111/tbed.13705. Online ahead of print.
Induction of Cross-Group Broadly Reactive Antibody Response by Natural H7N9 Avian Influenza Virus Infection and Immunization With Inactivated H7N9 Vaccine in Chickens
Zenglei Hu 1 2 3 4 , Lei Shi 3 4 , Naiqing Xu 3 4 , Xiaoquan Wang 3 4 , Jiao Hu 3 4 , Jiangyan Zhao 3 4 , Xiaowen Liu 3 4 , Shunlin Hu 3 4 , Min Gu 3 4 , Yongzhong Cao 1 2 , Xiufan Liu 1 2 3 4
AffiliationsExpand
- PMID: 32602258
- DOI: 10.1111/tbed.13705
Abstract
Pre-existing immunity against the conserved hemagglutinin (HA) stalk underlies the elicitation of cross-group antibody induced by natural H7N9 virus infection and immunization in humans. However, whether broadly reactive antibodies can be induced by H7N9 infection and immunization in the absence of pre-existing stalk-specific immunity is unclear. In this study, antibody response induced by H7N9 virus infection and immunization with inactivated and viral-vectored H7N9 vaccines in na?ve chickens was analyzed. The results showed that H7N9 infection and immunization with inactivated vaccine resulted in potent induction of hemagglutination-inhibition (HI), virus neutralization (VN) and HA-binding antibodies, whereas Newcastle disease virus (NDV)-vectored H7N9 vaccine induced marginal HI and VN titers but high levels of HA-binding antibody. In addition, H7N9 infection and immunization induced stalk-specific antibodies in na?ve chickens and these antibodies recognized different epitopes in the stalk. Virus infection and immunization with inactivated vaccine elicited antibodies cross-reactive with both group 1 and group 2 HAs, while antibodies induced by NDV-H7N9 vaccination showed a narrower cross-reactivity within group 2. Moreover, only homologous neutralizing activity of the sera against H7N9 virus was observed, and cross-binding antibodies did not show heterosubtypic neutralizing activity. Our results indicated that cross-group binding but non-neutralizing antibodies primarily targeting the stalk can be induced by natural H7N9 infection and immunization with inactivated vaccine in na?ve chickens. This suggests that at least in a na?ve chicken model, pre-existing stalk-specific immunity is not required for induction of broadly reactive antibodies. Additionally, H7N9-based immunogens may be explored as vaccine candidates or as a prime component to induce broadly protective influenza immunity.
Keywords: H7N9 avian influenza; HA stalk; antibody response; broadly-reactive; cross-group; immunization; virus infection.