6XSK

Cryo-EM Structure of Vaccine-Elicited Rhesus Antibody 789-203-3C12 in Complex with Stabilized SI06 (A/Solomon Islands/3/06) Influenza Hemagglutinin Trimer

Summary for 6XSK

• Entry DOI: 10.2210/pdb6xsk/pdb
• EMDB information: 22302
• Descriptor: 789-203-3C12 Fab Light Chain, 789-203-3C12 Fab Heavy Chain, Hemagglutinin HA1 chain, ... (7 entities in total)
• Functional Keywords: hemagglutinin ectodomain, prefusion conformation, vaccine-elicited antibody, disulfide-stabilized trimer, immune system, immune system-viral protein complex, immune system/viral protein
• Biological source: Macaca mulatta; More
• Total number of polymer chains: 12
• Total formula weight: 415748.85

Authors

Cerutti, G.,Gorman, J.,Kwong, P.D.,Shapiro, L. (deposition date: 2020-07-15, release date: 2021-07-21, Last modification date: 2024-10-16)

Primary citation

Moin, S.M.,Boyington, J.C.,Boyoglu-Barnum, S.,Gillespie, R.A.,Cerutti, G.,Cheung, C.S.,Cagigi, A.,Gallagher, J.R.,Brand, J.,Prabhakaran, M.,Tsybovsky, Y.,Stephens, T.,Fisher, B.E.,Creanga, A.,Ataca, S.,Rawi, R.,Corbett, K.S.,Crank, M.C.,Karlsson Hedestam, G.B.,Gorman, J.,McDermott, A.B.,Harris, A.K.,Zhou, T.,Kwong, P.D.,Shapiro, L.,Mascola, J.R.,Graham, B.S.,Kanekiyo, M.
Co-immunization with hemagglutinin stem immunogens elicits cross-group neutralizing antibodies and broad protection against influenza A viruses.
Immunity, 55:2405-2418.e7, 2022

PubMed Abstract: Current influenza vaccines predominantly induce immunity to the hypervariable hemagglutinin (HA) head, requiring frequent vaccine reformulation. Conversely, the immunosubdominant yet conserved HA stem harbors a supersite that is targeted by broadly neutralizing antibodies (bnAbs), representing a prime target for universal vaccines. Here, we showed that the co-immunization of two HA stem immunogens derived from group 1 and 2 influenza A viruses elicits cross-group protective immunity and neutralizing antibody responses in mice, ferrets, and nonhuman primates (NHPs). Immunized mice were protected from multiple group 1 and 2 viruses, and all animal models showed broad serum-neutralizing activity. A bnAb isolated from an immunized NHP broadly neutralized and protected against diverse viruses, including H5N1 and H7N9. Genetic and structural analyses revealed strong homology between macaque and human bnAbs, illustrating common biophysical constraints for acquiring cross-group specificity. Vaccine elicitation of stem-directed cross-group-protective immunity represents a step toward the development of broadly protective influenza vaccines.

PubMed: 36356572
DOI: 10.1016/j.immuni.2022.10.015

Experimental method

ELECTRON MICROSCOPY (3.85 Å)