Abstract
BackgroundInfluenza virus remains a continuous and severe threat to public health worldwide, and its prevention and treatment have always been a major international issue. Because of its ability to evade immune surveillance through rapid antigenic drift and antigenic shift, broad-spectrum vaccines seem increasingly important.MethodsA mAb named 3C12 from an immortalized hybrid cell was generated via immunizing mice with HA2 protein from A/chicken/Anhui/BRI99/2016 (AH/BRI99/16, H9N2) generated by prokaryotic expression. Then, its broad-spectrum activity was analyzed by WB and IFA. Next, the minimal linear epitope was identified via analyzing the reaction of a series of HA truncations with 3C12. Finally, the protective effects of 3C12 were evaluated in vitro and in vivo infection experiments.ResultsThe mAb could react with the viruses of subtypes H1, H2, H5, H8, H9, H12, H13, H16, and HA protein of H18 in group 1, but failed to react with viruses in group 2. The minimal linear epitope targeted by the mAb was 433NAELLVL439 in full length of HA and localized in the C-helix region of HA2 (residue 95-101, HA2 numbering). What’s more, the mAb 3C12 inhibited H1, H2, H5, H8, H9, H12, H13 and H16 virus-replication in vitro and also has shown effectiveness in preventing and treating disease in mice challenged with lethal dose of AH/BRI99/16 (H9N2) virus in vivo. These results suggested that the broadly reactive anti-HA stem mAb 3C12 exhibited prophylactic and therapeutic efficacy.ConclusionsHere, we have demonstrated that the linear epitope identified in this study could be a novel target for developing broad-spectrum influenza diagnostics or vaccine design, and the HA2-based monoclonal antibody is indeed a promising strategy for broad-spectrum protection against seasonal and pandemic influenza viruses.
Highlights
Influenza virus remains a continuous and severe threat to public health worldwide, and its prevention and treatment have always been a major international issue
Identification of monoclonal antibody binding to influenza A viruses of group 1 In this study, we generated several cross-reactive mouse monoclonal antibodies
To identify exactly which HA subtypes could be recognized by monoclonal antibodies (mAbs) 3C12, influenza A viruses of subtypes H1 through H16 and HA proteins for H17 and H18 were employed for reactivity testing
Summary
Influenza virus remains a continuous and severe threat to public health worldwide, and its prevention and treatment have always been a major international issue. Influenza viruses cause millions of cases of severe illness, thousands of deaths, and considerable economic losses each year [1]. According to the collecting data from World Health Organization (WHO), influenza A viruses (IAVs) annually cause about 3 to 5 million cases of severe illness and approximately 290,000 to 650,000 respiratory deaths worldwide [2]. IAVs possess eight segmented, negative-sense viral RNAs (vRNAs) as its genome. Two of these vRNAs encode hemagglutinin (HA) and neuraminidase (NA), which are major viral antigenic proteins on the virus particle [5]. Current commercial vaccines of IAVs are still strain-specific and show only limited protective efficacy against the emerging strains with antigenic drift or shift [20, 21]. A broad-spectrum vaccine against all the 18 HA subtypes is highly required for protection against epidemics or pandemics of IAVs in both human and animals
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