6ORO

Modified BG505 SOSIP-based immunogen RC1 in complex with the elicited V3-glycan patch antibody Ab874NHP

Summary for 6ORO

• Entry DOI: 10.2210/pdb6oro/pdb
• EMDB information: 20176
• Descriptor: RC1 variant of HIV-1 Env glycoprotein gp41, RC1 variant of HIV-1 Env glycoprotein gp120, Ab874NHP antibody Fab heavy chain, ... (9 entities in total)
• Functional Keywords: hiv-1 broadly-neutralizing antibody, env trimer structure, v3-glycan patch, cryo-em, rc1, immunogen design, antiviral protein-immune system complex, antiviral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 12
• Total formula weight: 388288.09

Authors

Abernathy, M.E.,Gristick, H.B.,Bjorkman, P.J. (deposition date: 2019-04-30, release date: 2019-06-12, Last modification date: 2020-07-29)

Primary citation

Escolano, A.,Gristick, H.B.,Abernathy, M.E.,Merkenschlager, J.,Gautam, R.,Oliveira, T.Y.,Pai, J.,West Jr., A.P.,Barnes, C.O.,Cohen, A.A.,Wang, H.,Golijanin, J.,Yost, D.,Keeffe, J.R.,Wang, Z.,Zhao, P.,Yao, K.H.,Bauer, J.,Nogueira, L.,Gao, H.,Voll, A.V.,Montefiori, D.C.,Seaman, M.S.,Gazumyan, A.,Silva, M.,McGuire, A.T.,Stamatatos, L.,Irvine, D.J.,Wells, L.,Martin, M.A.,Bjorkman, P.J.,Nussenzweig, M.C.
Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques.
Nature, 570:468-473, 2019

PubMed Abstract: Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it has not yet been possible to induce adequate serological responses by vaccination. Here, to activate B cells that express precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed an immunogen, RC1, that facilitates the recognition of the variable loop 3 (V3)-glycan patch on the envelope protein of HIV-1. RC1 conceals non-conserved immunodominant regions by the addition of glycans and/or multimerization on virus-like particles. Immunization of mice, rabbits and rhesus macaques with RC1 elicited serological responses that targeted the V3-glycan patch. Antibody cloning and cryo-electron microscopy structures of antibody-envelope complexes confirmed that immunization with RC1 expands clones of B cells that carry the anti-V3-glycan patch antibodies, which resemble precursors of human broadly neutralizing antibodies. Thus, RC1 may be a suitable priming immunogen for sequential vaccination strategies in the context of polyclonal repertoires.

PubMed: 31142836
DOI: 10.1038/s41586-019-1250-z

Experimental method

ELECTRON MICROSCOPY (3.9 Å)