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Vaccine Induction of Heterologous Tier 2 HIV-1 Neutralizing Antibodies in Animal Models.
- Source :
-
Cell reports [Cell Rep] 2017 Dec 26; Vol. 21 (13), pp. 3681-3690. - Publication Year :
- 2017
-
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 (V <subscript>H</subscript> DJ <subscript>H</subscript> ) knockin mice similarly induced V1V2-glycan neutralizing antibodies (nAbs), wherein the human CD4bs V <subscript>H</subscript>  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 <subscript>H</subscript> replacement and diversity region fusion as potential mechanisms for generating V1V2-glycan bnAb site antibodies.<br /> (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Amino Acid Sequence
Animals
Disease Models, Animal
Epitopes chemistry
Epitopes immunology
Immunization
Macaca mulatta
Mice
Polysaccharides immunology
Protein Multimerization
Rabbits
env Gene Products, Human Immunodeficiency Virus immunology
AIDS Vaccines immunology
Antibodies, Neutralizing immunology
HIV Antibodies immunology
HIV-1 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 21
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 29281818
- Full Text :
- https://doi.org/10.1016/j.celrep.2017.12.028