A human monoclonal antibody derived from a vaccinated volunteer recognizes heterosubtypically a novel epitope on the hemagglutinin globular head of H1 and H9 influenza A viruses

Abstract

Most neutralizing antibodies elicited during influenza virus infection or by vaccination have a narrow spectrum because they usually target variable epitopes in the globular head region of hemagglutinin (HA). In this study, we describe a human monoclonal antibody (HuMAb), 5D7, that was prepared from the peripheral blood lymphocytes of a vaccinated volunteer using the fusion method. The HuMAb heterosubtypically neutralizes group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H9N2, with a strong hemagglutinin inhibition activity. Selection of an escape mutant showed that the HuMAb targets a novel conformational epitope that is located in the HA head region but is distinct from the receptor binding site. Furthermore, Phe114Ile substitution in the epitope made the HA unrecognizable by the HuMAb. Amino acid residues in the predicted epitope region are also highly conserved in the HAs of H1N1 and H9N2. The HuMAb reported here may be a potential candidate for the development of therapeutic/prophylactic antibodies against H1 and H9 influenza viruses.

Universal Influenza Virus Vaccines That Target the Conserved Hemagglutinin Stalk and Conserved Sites in the Head Domain

“…In addition, antibodies that cross-react between the head domains of different H1 or H3 strains have been isolated as well, although they seem to be relatively rare [41][42][43][44][45][46]. Furthermore, a small number of mAbs that show cross-reactivity between the head domains of different HA subtypes have been reported [47][48][49][50][51]. While these antibodies are rare, they are interesting since they suggest that cross-reactive epitopes in the head domains of HAs exist as well.…”

Flu Universal Vaccines: New Tricks on an Old Virus

“…As mentioned above, HA head domain is the major target of the antibody response following vaccination with seasonal influenza vaccines, however its high plasticity makes it easy for the virus to escape immune pressure (Heaton et al 2013 ). Despite of this, monoclonal antibodies (mAbs) that cross-react between the head domains of different HA subtypes have been reported (Ekiert et al 2012 ; Krause et al 2012 ; Lee et al 2012 ; Boonsathorn et al 2014 ; Lee et al 2014 ). These cross-reactive head antibodies seem rare, but they are interesting since they suggest the existence of cross-reactive epitopes in the head domains.…”

Clinical Expectations for Better Influenza Virus Vaccines—Perspectives from the Young Investigators’ Point of View

“…The phenomenon of heterosubtypic immunity [ 79 , 80 , 81 ], where host immune responses towards conserved viral epitopes cover several influenza subtypes, is of foremost interest in the development of next generation influenza vaccines. Although heterosubtypic antibodies have been shown to occur and to play a role in heterosubtypic immunity [ 82 , 83 , 84 ], historically cross-reactive cytotoxic T lymphocytes recognizing conserved internal epitopes have been the major focus of research [ 85 , 86 ]. Numerous studies demonstrate that individuals possess CD4 and CD8 T-cells with cross-reactivity to influenza A virus strains for which they have not been previously exposed [ 74 , 87 , 88 , 89 , 90 , 91 ].…”