Rapid development of glycan-specific, broad, and potent anti-HIV-1 gp120 neutralizing antibodies in an R5 SIV/HIV chimeric virus infected macaque.

TitleRapid development of glycan-specific, broad, and potent anti-HIV-1 gp120 neutralizing antibodies in an R5 SIV/HIV chimeric virus infected macaque.
Publication TypeJournal Article
Year of Publication2011
AuthorsWalker LM, Sok D, Nishimura Y, Donau O, Sadjadpour R, Gautam R, Shingai M, Pejchal R, Ramos A, Simek MD, Geng Y, Wilson IA, Poignard P, Martin MA, Burton DR
JournalProc Natl Acad Sci U S A
Volume108
Issue50
Pagination20125-9
Date Published2011 Dec 13
ISSN1091-6490
KeywordsAnimals, Antibodies, Neutralizing, Antibodies, Viral, Antibody Specificity, HIV, HIV Envelope Protein gp120, HIV Infections, Macaca, Neutralization Tests, Polysaccharides, Protein Binding, Recombination, Genetic, Simian Acquired Immunodeficiency Syndrome, Simian immunodeficiency virus
Abstract

It is widely believed that the induction of a broadly neutralizing antibody (bNAb) response will be a critical component of a successful vaccine against HIV. A significant fraction of HIV-infected individuals mount bNAb responses, providing support for the notion that such responses could be elicited through vaccination. Infection of macaques with simian immunodeficiency virus (SIV) or SIV/HIV chimeric virus (SHIV) has been widely used to model aspects of HIV infection, but to date, only limited bNAb responses have been described. Here, we screened plasma from 14 R5-tropic SHIV-infected macaques for broadly neutralizing activity and identified a macaque with highly potent cross-clade plasma NAb response. Longitudinal studies showed that the development of broad and autologous NAb responses occurred coincidentally in this animal. Serum-mapping studies, using pseudovirus point mutants and antigen adsorption assays, indicated that the plasma bNAbs are specific for epitopes that include carbohydrates and are critically dependent on the glycan at position 332 of Env gp120. The results described herein provide insight into the development and evolution of a broad response, suggest that certain bNAb specificities may be more rapidly induced by immunization than others, and provide a potential model for the facile study of the development of bNAb responses.

DOI10.1073/pnas.1117531108
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID22123961