title: Rapid development of glycan-specific, broad, and potent anti-HIV-1 gp120 neutralizing antibodies in an R5 SIV/HIV chimeric virus infected macaque.
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.
authors: Department of Immunology and Microbial Science and International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors: Laura M
authors: LM
authors: Walker
authors: Devin
authors: D
authors: Sok
authors: Yoshiaki
authors: Y
authors: Nishimura
authors: Olivia
authors: O
authors: Donau
authors: Reza
authors: R
authors: Sadjadpour
authors: Rajeev
authors: R
authors: Gautam
authors: Masashi
authors: M
authors: Shingai
authors: Robert
authors: R
authors: Pejchal
authors: Alejandra
authors: A
authors: Ramos
authors: Melissa D
authors: MD
authors: Simek
authors: Yu
authors: Y
authors: Geng
authors: Ian A
authors: IA
authors: Wilson
authors: Pascal
authors: P
authors: Poignard
authors: Malcolm A
authors: MA
authors: Martin
authors: Dennis R
authors: DR
authors: Burton
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology*; D006678:HIV / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology / Q000821:virology; D008251:Macaca / Q000097:blood / Q000276:immunology* / Q000821:virology; D009500:Neutralization Tests; D011134:Polysaccharides / Q000276:immunology*; D011485:Protein Binding; D011995:Recombination, Genetic / Q000235:genetics; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015699:HIV Envelope Protein gp120; D011134:Polysaccharides