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Vaccine Induction of Heterologous Tier 2 HIV-1 Neutralizing Antibodies in Animal Models.


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.

SUBMITTER: Saunders KO 

PROVIDER: S-EPMC5777169 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Vaccine Induction of Heterologous Tier 2 HIV-1 Neutralizing Antibodies in Animal Models.

Saunders Kevin O KO   Verkoczy Laurent K LK   Jiang Chuancang C   Zhang Jinsong J   Parks Robert R   Chen Haiyan H   Housman Max M   Bouton-Verville Hilary H   Shen Xiaoying X   Trama Ashley M AM   Scearce Richard R   Sutherland Laura L   Santra Sampa S   Newman Amanda A   Eaton Amanda A   Xu Kai K   Georgiev Ivelin S IS   Joyce M Gordon MG   Tomaras Georgia D GD   Bonsignori Mattia M   Reed Steven G SG   Salazar Andres A   Mascola John R JR   Moody M Anthony MA   Cain Derek W DW   Centlivre Mireille M   Zurawski Sandra S   Zurawski Gerard G   Erickson Harold P HP   Kwong Peter D PD   Alam S Munir SM   Levy Yves Y   Montefiori David C DC   Haynes Barton F BF  

Cell reports 20171201 13


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 im  ...[more]

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