Abstract
A systemic evaluation of the antigenic differences of the H7 influenza hemagglutinin (HA) proteins, especially for the viruses isolated after 2016, are limited. The purpose of this study was to investigate the antigenic differences of major H7 strains with an ultimate aim to discover H7 HA proteins that can elicit protective receptor-binding antibodies against co-circulating H7 influenza strains. A panel of eight H7 influenza strains were selected from 3,633 H7 HA amino acid sequences identified over the past two decades (2000-2018). The sequences were expressed on the surface of virus like particles (VLPs) and used to vaccinate C57BL/6 mice. Serum samples were collected and tested for hemagglutination-inhibition (HAI) activity. The vaccinated mice were challenged with lethal dose of H7N9 virus, A/Anhui/1/2013. VLPs expressing the H7 HA antigens elicited broadly reactive antibodies each of the selected H7 HAs, except the A/Turkey/Italy/589/2000 (Italy/00) H7 HA. A putative glycosylation due to an A169T substitution in antigenic site B was identified as a unique antigenic profile of Italy/00. Introduction of the putative glycosylation site (H7 HA-A169T) significantly altered the antigenic profile of HA of the A/Anhui/1/2013 (H7N9) strain. This study identified key amino acid mutations that result in severe vaccine mismatches for future H7 epidemics. Future universal influenza vaccine candidates will need to focus on viral variants with these key mutations.
Highlights
Avian-origin influenza A hemagglutinin subtype 7 viruses (H7 AI viruses) circulate primarily in avian hosts
Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; we enable the publication of all of the content of peer review and author responses alongside final, published articles
virus like particles (VLPs) expressing the H7 HA antigens elicited broadly reactive antibodies each of the selected H7 HAs, except the A/Turkey/Italy/589/2000 (Italy/00) H7 HA
Summary
Avian-origin influenza A hemagglutinin subtype 7 viruses (H7 AI viruses) circulate primarily in avian hosts. H7 influenza virus strains have caused at least five human epidemics since 2000: 1) the H7N1 influenza viruses infected people in Italy, 2) the H7N2 influenza viruses infected people in Northeastern U.S, 3) two distinct H7N3 influenza viruses infected people in North American and Eurasian countries, 4) one H7N4 infection case in China in 2018, and 5) people in Europe were infected with H7N7 influenza viruses [8]. These epidemics warrant that another avian influenza virus of the H7 subtype may infect and begin transmitting between humans to initiate the H7 influenza virus pandemic.
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