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

PLoS Pathogens

Linda-Gail Bekker¹  Adam Godzik²  Matt A. Price²  Ben Murrell²  William Kilembe³  Pham Phung⁴  Shane Crotty⁵  Etienne Karita⁶  Lalinda Wickramasinghe⁶  Charoan B. Bian⁷  Elise Landais⁷  Melissa Simek⁷  Susan Allen⁷  Jill Gilmour⁸  Colin Havenar-Daughton⁹  Vinodh Edward^1,10  Pascal Poignard^1,11  Jianming Tang^1,12  Omu Anzala^1,13  Anatoli Kamali^1,13  Eduard J. Sanders^1,13  Shabir Lakhi^1,13  Mubiana Inambao^1,14  Xiayu Huang^1,15  Sergei L. Kosakovsky-Pond^1,16  Terri Wrin^1,17  Alejandra Ramos^1,18 

[1] Centre for Geographic Medicine-Coast, Kenya Medical Research Institute, Kilifi, Kenya;Department of Medicine, University of California San Diego, San Diego, California, United States of America;Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, Georgia, United States of America;Desmond Tutu HIV Center, University of Cape Town, Cape Town, South Africa;IAVI Human Immunology Laboratory, Imperial College of Science Technology and Medicine, Chelsea & Westminster Hospital, London, United Kingdom;IAVI Medical Affairs, New York, New York, United States of America;International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center, La Jolla, California, United States of America;Kenya AIDS Vaccine Initiative, Nairobi, Kenya;La Jolla Institute for Allergy and Immunology (LIAI), La Jolla, California, United States of America;MRC/UVRI Uganda Research Unit on AIDS, Masaka & Entebbe, Uganda;Monogram Biosciences, Laboratory Corporation of America® Holdings, San Francisco California, United States of America;Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom;Rwanda-Zambia HIV Research Group, Lusaka & Ndola, Zambia;Rwanda-Zambia HIV Research Group, Project San Francisco, Kigali, Rwanda;Sanford-Burnham Medical Research Institute, La Jolla, California, United States of America;The Aurum Institute, Parktown, Johannesburg, South Africa;University of Alabama Birmingham, Department of Epidemiology and Department of Medicine, Birmingham, Alabama, United States of America;University of California San Francisco Department of Epidemiology and Biostatistics, San Francisco, California, United States of America

关键词: HIV-1;    Viral load;    Antibody response;    Antibodies;    HIV-2;    Adsorption;    HIV;    T helper cells;   

DOI  :  10.1371/journal.ppat.1005369

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY