Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort.

• Type of Material: Article
• Authors: Elise Landais, International AIDS Vaccine Initiative (IAVI); Xiayu Huang, Sanford-Burnham Medical Research Institute; Colin Havenar-Daughton, La Jolla Institute for Allergy and Immunology (LIAI); Ben Murrell, University of California San Diego; Matt A. Price, International AIDS Vaccine Initiative (IAVI); Lalinda Wickramasinghe, International AIDS Vaccine Initiative (IAVI); Alejandra Ramos, International AIDS Vaccine Initiative (IAVI); Charoan B. Bian, International AIDS Vaccine Initiative (IAVI); Melissa Simek, International AIDS Vaccine Initiative (IAVI); Susan Allen, Emory University; Etienne Karita, Rwanda-Zambia HIV Research Group; William Kilembe, Rwanda-Zambia HIV Research Group; Shabir Lakhi, Rwanda-Zambia HIV Research Group; Mubiana Inambao, Rwanda-Zambia HIV Research Group; Anatoli Kamali, MRC/UVRI Uganda Research Unit on AIDS; Eduard J. Sanders, Kenya Medical Research Institute; Omu Anzala, Kenya AIDS Vaccine Initiative; Vinodh Edward, The Aurum Institute; Linda-Gail Bekker, University of Cape Town; Jianming Tang, University of Alabama Birmingham; Jill Gilmour, International AIDS Vaccine Initiative (IAVI); Sergei L. Kosakovsky-Pond, University of California San Diego; Pham Phung, Laboratory Corporation of America® Holdings; Terri Wrin, Laboratory Corporation of America® Holdings; Shane Crotty, La Jolla Institute for Allergy and Immunology (LIAI); Adam Godzik, Sanford-Burnham Medical Research Institute; Pascal Poignard, International AIDS Vaccine Initiative (IAVI)
• Language: English
• Date: 2016-01
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2016 Landais et al
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.ppat.1005369
• Title of Journal or Parent Work: PLoS Pathogens
• ISSN: 1553-7366
• Volume: 12
• Issue: 1
• Start Page: e1005369
• End Page: e1005369
• Grant/Funding Information: This work was funded in part by IAVI and made possible by the support of the United States Agency for International Development (USAID) and other donors. The full list of IAVI donors is available at http://www.iavi.org.; The project described was supported by Awards Number U19AI090970 and UM1AI100663 from the National Institute Of Allergy And Infectious Diseases.; BM is also supported by the Award Numbers U01GM110749 from the National Institute of General Medical Sciences.
• Keywords: T helper cells; HIV-1; Viral load; HIV; Antibodies; Adsorption; HIV-2; Antibody response
• Research Categories: Biology, Virology; Health Sciences, Immunology

Abstract

Broadly neutralizing antibodies (bnAbs) are thought to be a critical component of a protective HIV vaccine. However, designing vaccines immunogens able to elicit bnAbs has proven unsuccessful to date. Understanding the correlates and immunological mechanisms leading to the development of bnAb responses during natural HIV infection is thus critical to the design of a protective vaccine. The IAVI Protocol C program investigates a large longitudinal cohort of primary HIV-1 infection in Eastern and South Africa. Development of neutralization was evaluated in 439 donors using a 6 cross-clade pseudo-virus panel predictive of neutralization breadth on larger panels. About 15% of individuals developed bnAb responses, essentially between year 2 and year 4 of infection. Statistical analyses revealed no influence of gender, age or geographical origin on the development of neutralization breadth. However, cross-clade neutralization strongly correlated with high viral load as well as with low CD4 T cell counts, subtype-C infection and HLA-A*03(-) genotype. A correlation with high overall plasma IgG levels and anti-Env IgG binding titers was also found. The latter appeared not associated with higher affinity, suggesting a greater diversity of the anti-Env responses in broad neutralizers. Broadly neutralizing activity targeting glycan-dependent epitopes, largely the N332-glycan epitope region, was detected in nearly half of the broad neutralizers while CD4bs and gp41-MPER bnAb responses were only detected in very few individuals. Together the findings suggest that both viral and host factors are critical for the development of bnAbs and that the HIV Env N332-glycan supersite may be a favorable target for vaccine design.