A Broadly Neutralizing Human Monoclonal Antibody That Recognizes a Conserved, Novel Epitope on the Globular Head of the Influenza H1N1 Virus Hemagglutinin

Abstract

The conserved influenza virus hemagglutinin (HA) stem domain elicits cross-reactive antibodies, but epitopes in the globular head typically elicit strain-specific responses because of the hypervariability of this region. We isolated human monoclonal antibody 5J8, which neutralized a broad spectrum of 20th century H1N1 viruses and the 2009 pandemic H1N1 virus. Fine mapping of the interaction unexpectedly revealed a novel epitope between the receptor-binding pocket and the Ca 2 antigenic site on HA. This antibody exposes a new mechanism underlying broad immunity against H1N1 influenza viruses and identifies a conserved epitope that might be incorporated into engineered H1 virus vaccines.

Human Monoclonal Antibodies to Pandemic 1957 H2N2 and Pandemic 1968 H3N2 Influenza Viruses

“…Peripheral blood mononuclear cells (PBMCs) were isolated, Epstein Barr virus (EBV) transformed in 384-well plates (Nunc) in the presence of 2.5 g/ml CpG ODN 2006 (InvivoGen), 10 M Chk2 inhibitor II (Sigma; catalog no. C3742), and 1 g/ml cyclosporine (Sigma), essentially as previously described (15,16,53,54). The antibodies described can be obtained for research purposes under a materials transfer agreement.…”

Fc functional antibodies in humans with severe H7N9 and seasonal influenza

“…Humoral immunity has long been implicated in protection from influenza through NAbs that block virus entry into cells (12,13). The narrow specificity of influenza NAbs, particularly those directed against the immunodominant hemagglutinin (HA) head, is problematic for protection against influenza viruses (14,15).…”

Antibody-Dependent Cellular Cytotoxicity Is Associated with Control of Pandemic H1N1 Influenza Virus Infection of Macaques

“…Recent evidence suggests that at least some infected hosts are capable of producing such antibodies, which commonly target the membrane-proximal region of HA (stem) and either inhibit fusion of viral and endosomal membranes, inhibit viral egress, or inhibit HA maturation (8)(9)(10)(11)(12). At least some such antibodies are capable of neutralizing all 16 subtypes of influenza viruses in vitro, and they protect mice and ferrets against lethal challenges with H1N1 and H5N1 viruses, respectively (13,14).…”