| Literature DB >> 29281818 |
Kevin O Saunders1, Laurent K Verkoczy2, Chuancang Jiang3, Jinsong Zhang3, Robert Parks3, Haiyan Chen3, Max Housman4, Hilary Bouton-Verville3, Xiaoying Shen3, Ashley M Trama3, Richard Scearce3, Laura Sutherland3, Sampa Santra5, Amanda Newman3, Amanda Eaton6, Kai Xu7, Ivelin S Georgiev7, M Gordon Joyce7, Georgia D Tomaras6, Mattia Bonsignori3, Steven G Reed8, Andres Salazar9, John R Mascola7, M Anthony Moody10, Derek W Cain3, Mireille Centlivre11, Sandra Zurawski12, Gerard Zurawski12, Harold P Erickson4, Peter D Kwong7, S Munir Alam13, Yves Levy11, David C Montefiori6, Barton F Haynes14.
Abstract
The events required for the induction of broad neutralizing antibodies (bnAbs) following HIV-1 envelope (Env) vaccination are unknown, and their induction in animal models as proof of concept would be critical. Here, we describe the induction of plasma antibodies capable of neutralizing heterologous primary (tier 2) HIV-1 strains in one macaque and two rabbits. Env immunogens were designed to induce CD4 binding site (CD4bs) bnAbs, but surprisingly, the macaque developed V1V2-glycan bnAbs. Env immunization of CD4bs bnAb heavy chain rearrangement (VHDJH) knockin mice similarly induced V1V2-glycan neutralizing antibodies (nAbs), wherein the human CD4bs VH chains were replaced with mouse rearrangements bearing diversity region (D)-D fusions, creating antibodies with long, tyrosine-rich HCDR3s. Our results show that Env vaccination can elicit broad neutralization of tier 2 HIV-1, demonstrate that V1V2-glycan bnAbs are more readily induced than CD4bs bnAbs, and define VH replacement and diversity region fusion as potential mechanisms for generating V1V2-glycan bnAb site antibodies.Entities:
Keywords: CH103; CH505; HIV vaccine; broadly neutralizing antibodies; knockin mice
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Year: 2017 PMID： 29281818 PMCID： PMC5777169 DOI： 10.1016/j.celrep.2017.12.028
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423