6orq

Modified BG505 SOSIP-based immunogen RC1 in complex with the elicited V3-glycan patch antibody Ab275MURModified BG505 SOSIP-based immunogen RC1 in complex with the elicited V3-glycan patch antibody Ab275MUR

6orq, resolution 4.40Å

Structural highlights

6orq is a 12 chain structure with sequence from 9hiv1 and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Experimental data:	Check
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

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.

Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques.,Escolano A, Gristick HB, Abernathy ME, Merkenschlager J, Gautam R, Oliveira TY, Pai J, West AP Jr, Barnes CO, Cohen AA, Wang H, Golijanin J, Yost D, Keeffe JR, Wang Z, Zhao P, Yao KH, Bauer J, Nogueira L, Gao H, Voll AV, Montefiori DC, Seaman MS, Gazumyan A, Silva M, McGuire AT, Stamatatos L, Irvine DJ, Wells L, Martin MA, Bjorkman PJ, Nussenzweig MC Nature. 2019 May 29. pii: 10.1038/s41586-019-1250-z. doi:, 10.1038/s41586-019-1250-z. PMID:31142836^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Escolano A, Gristick HB, Abernathy ME, Merkenschlager J, Gautam R, Oliveira TY, Pai J, West AP Jr, Barnes CO, Cohen AA, Wang H, Golijanin J, Yost D, Keeffe JR, Wang Z, Zhao P, Yao KH, Bauer J, Nogueira L, Gao H, Voll AV, Montefiori DC, Seaman MS, Gazumyan A, Silva M, McGuire AT, Stamatatos L, Irvine DJ, Wells L, Martin MA, Bjorkman PJ, Nussenzweig MC. Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques. Nature. 2019 May 29. pii: 10.1038/s41586-019-1250-z. doi:, 10.1038/s41586-019-1250-z. PMID:31142836 doi:http://dx.doi.org/10.1038/s41586-019-1250-z

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OCA

[1] Escolano A, Gristick HB, Abernathy ME, Merkenschlager J, Gautam R, Oliveira TY, Pai J, West AP Jr, Barnes CO, Cohen AA, Wang H, Golijanin J, Yost D, Keeffe JR, Wang Z, Zhao P, Yao KH, Bauer J, Nogueira L, Gao H, Voll AV, Montefiori DC, Seaman MS, Gazumyan A, Silva M, McGuire AT, Stamatatos L, Irvine DJ, Wells L, Martin MA, Bjorkman PJ, Nussenzweig MC. Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques. Nature. 2019 May 29. pii: 10.1038/s41586-019-1250-z. doi:, 10.1038/s41586-019-1250-z. PMID:31142836 doi:http://dx.doi.org/10.1038/s41586-019-1250-z

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