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Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques.

<div class='caption-title'>Characterization of the RC1 immunogen.</div>
<div class='caption-title'>Wild-type mouse immunization with RC1 elicits V3-glycan patchantibodies.</div>
<div class='caption-title'>Macaque immunization with RC1–4fill VLPs elicits anti-V3-glycan patchantibodies that resemble iGLs of bNAbs.</div>
Escolano A, Gristick HB, Abernathy ME, Merkenschlager J, Gautam R, Oliveira TY, Pai J, West AP, 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
OpenAccess logo Nature 570 468-473 (2019)
Related entries: 6oro, 6orp, 6orq

Cited: 108 times
EuropePMC logo PMID: 31142836

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.

Articles - 6orn mentioned but not cited (4)

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  3. Sequential immunization of macaques elicits heterologous neutralizing antibodies targeting the V3-glycan patch of HIV-1 Env. Escolano A, Gristick HB, Gautam R, DeLaitsch AT, Abernathy ME, Yang Z, Wang H, Hoffmann MAG, Nishimura Y, Wang Z, Koranda N, Kakutani LM, Gao H, Gnanapragasam PNP, Raina H, Gazumyan A, Cipolla M, Oliveira TY, Ramos V, Irvine DJ, Silva M, West AP, Keeffe JR, Barnes CO, Seaman MS, Nussenzweig MC, Martin MA, Bjorkman PJ. Sci Transl Med 13 eabk1533 (2021)
  4. A broadly neutralizing macaque monoclonal antibody against the HIV-1 V3-Glycan patch. Wang Z, Barnes CO, Gautam R, Cetrulo Lorenzi JC, Mayer CT, Oliveira TY, Ramos V, Cipolla M, Gordon KM, Gristick HB, West AP, Nishimura Y, Raina H, Seaman MS, Gazumyan A, Martin M, Bjorkman PJ, Nussenzweig MC, Escolano A. Elife 9 e61991 (2020)


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