6XGC

CryoEM structure of influenza hemagglutinin A/Michigan/45/2015 in complex with cyno antibody 1C4

Summary for 6XGC

• Entry DOI: 10.2210/pdb6xgc/pdb
• EMDB information: 22180
• Descriptor: Hemagglutinin HA1 chain, Hemagglutinin HA2 chain, 1C4 Fab heavy chain, ... (6 entities in total)
• Functional Keywords: influenza, hemagglutinin, antibody, vaccine, broadly neutralizing antibody, antiviral protein
• Biological source: Influenza A virus (A/Michigan/45/2015(H1N1)); More
• Total number of polymer chains: 12
• Total formula weight: 334547.85

Authors

Qiu, Y.,Zhou, Y. (deposition date: 2020-06-17, release date: 2021-03-10, Last modification date: 2025-05-21)

Primary citation

Darricarrere, N.,Qiu, Y.,Kanekiyo, M.,Creanga, A.,Gillespie, R.A.,Moin, S.M.,Saleh, J.,Sancho, J.,Chou, T.H.,Zhou, Y.,Zhang, R.,Dai, S.,Moody, A.,Saunders, K.O.,Crank, M.C.,Mascola, J.R.,Graham, B.S.,Wei, C.J.,Nabel, G.J.
Broad neutralization of H1 and H3 viruses by adjuvanted influenza HA stem vaccines in nonhuman primates.
Sci Transl Med, 13:-, 2021

PubMed Abstract: Seasonal influenza vaccines confer protection against specific viral strains but have restricted breadth that limits their protective efficacy. The H1 and H3 subtypes of influenza A virus cause most of the seasonal epidemics observed in humans and are the major drivers of influenza A virus-associated mortality. The consequences of pandemic spread of COVID-19 underscore the public health importance of prospective vaccine development. Here, we show that headless hemagglutinin (HA) stabilized-stem immunogens presented on ferritin nanoparticles elicit broadly neutralizing antibody (bnAb) responses to diverse H1 and H3 viruses in nonhuman primates (NHPs) when delivered with a squalene-based oil-in-water emulsion adjuvant, AF03. The neutralization potency and breadth of antibodies isolated from NHPs were comparable to human bnAbs and extended to mismatched heterosubtypic influenza viruses. Although NHPs lack the immunoglobulin germline VH1-69 residues associated with the most prevalent human stem-directed bnAbs, other gene families compensated to generate bnAbs. Isolation and structural analyses of vaccine-induced bnAbs revealed extensive interaction with the fusion peptide on the HA stem, which is essential for viral entry. Antibodies elicited by these headless HA stabilized-stem vaccines neutralized diverse H1 and H3 influenza viruses and shared a mode of recognition analogous to human bnAbs, suggesting that these vaccines have the potential to confer broadly protective immunity against diverse viruses responsible for seasonal and pandemic influenza infections in humans.

PubMed: 33658355
DOI: 10.1126/scitranslmed.abe5449

Experimental method

ELECTRON MICROSCOPY (4.1 Å)