6VBO

Crystal structure of anti-HIV-1 antibody DH813 bound to gp120 V2 peptide

Summary for 6VBO

• Entry DOI: 10.2210/pdb6vbo/pdb
• Descriptor: DH813 light chain, DH813 heavy chain, Envelope glycoprotein gp160, ... (4 entities in total)
• Functional Keywords: antibody, gp120 v2, rv305/rv144, immune system, immune system-viral protein complex, immune system/viral protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 50134.06

Authors

Janus, B.M.,Ofek, G. (deposition date: 2019-12-19, release date: 2020-02-12, Last modification date: 2024-10-16)

Primary citation

Easterhoff, D.,Pollara, J.,Luo, K.,Janus, B.,Gohain, N.,Williams, L.D.,Tay, M.Z.,Monroe, A.,Peachman, K.,Choe, M.,Min, S.,Lusso, P.,Zhang, P.,Go, E.P.,Desaire, H.,Bonsignori, M.,Hwang, K.K.,Beck, C.,Kakalis, M.,O'Connell, R.J.,Vasan, S.,Kim, J.H.,Michael, N.L.,Excler, J.L.,Robb, M.L.,Rerks-Ngarm, S.,Kaewkungwal, J.,Pitisuttithum, P.,Nitayaphan, S.,Sinangil, F.,Tartaglia, J.,Phogat, S.,Wiehe, K.,Saunders, K.O.,Montefiori, D.C.,Tomaras, G.D.,Moody, M.A.,Arthos, J.,Rao, M.,Joyce, M.G.,Ofek, G.A.,Ferrari, G.,Haynes, B.F.
HIV vaccine delayed boosting increases Env variable region 2-specific antibody effector functions.
JCI Insight, 5:-, 2020

PubMed Abstract: In the RV144 HIV-1 phase III trial, vaccine efficacy directly correlated with the magnitude of the variable region 2-specific (V2-specific) IgG antibody response, and in the presence of low plasma IgA levels, with the magnitude of plasma antibody-dependent cellular cytotoxicity. Reenrollment of RV144 vaccinees in the RV305 trial offered the opportunity to define the function, maturation, and persistence of vaccine-induced V2-specific and other mAb responses after boosting. We show that the RV144 vaccine regimen induced persistent V2 and other HIV-1 envelope-specific memory B cell clonal lineages that could be identified throughout the approximately 11-year vaccination period. Subsequent boosts increased somatic hypermutation, a critical requirement for antibody affinity maturation. Characterization of 22 vaccine-induced V2-specific mAbs with epitope specificities distinct from previously characterized RV144 V2-specific mAbs CH58 and CH59 found increased in vitro antibody-mediated effector functions. Thus, when inducing non-neutralizing antibodies, one method by which to improve HIV-1 vaccine efficacy may be through late boosting to diversify the V2-specific response to increase the breadth of antibody-mediated anti-HIV-1 effector functions.

PubMed: 31996483
DOI: 10.1172/jci.insight.131437

Experimental method

X-RAY DIFFRACTION (1.683 Å)