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

Saunders KO, Verkoczy LK, Jiang C, Zhang J, Parks R, Chen H, Housman M, Bouton-Verville H, Shen X, Trama AM, Scearce R, Sutherland L, Santra S, Newman A, Eaton A, Xu K, Georgiev IS, Joyce MG, Tomaras GD, Bonsignori M, Reed SG, Salazar A, Mascola JR, Moody MA, Cain DW, Centlivre M, Zurawski S, Zurawski G, Erickson HP, Kwong PD, Alam SM, Levy Y, Montefiori DC, Haynes BF
Cell Rep. 2017 21 (13): 3681-3690

PMID: 29281818 · PMCID: PMC5777169 · DOI:10.1016/j.celrep.2017.12.028

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 (VDJ) knockin mice similarly induced V1V2-glycan neutralizing antibodies (nAbs), wherein the human CD4bs V 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 V replacement and diversity region fusion as potential mechanisms for generating V1V2-glycan bnAb site antibodies.

Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

MeSH Terms (15)

AIDS Vaccines Amino Acid Sequence Animals Antibodies, Neutralizing Disease Models, Animal env Gene Products, Human Immunodeficiency Virus Epitopes HIV-1 HIV Antibodies Immunization Macaca mulatta Mice Polysaccharides Protein Multimerization Rabbits

Connections (1)

This publication is referenced by other Labnodes entities: