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PLoS Pathog. 2016 Jan 14;12(1):e1005369. doi: 10.1371/journal.ppat.1005369. eCollection 2016 Jan.

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

Author information

1
International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center, La Jolla, California, United States of America.
2
Sanford-Burnham Medical Research Institute, La Jolla, California, United States of America.
3
La Jolla Institute for Allergy and Immunology (LIAI), La Jolla, California, United States of America.
4
Department of Medicine, University of California San Diego, San Diego, California, United States of America.
5
IAVI Medical Affairs, New York, New York, United States of America.
6
University of California San Francisco Department of Epidemiology and Biostatistics, San Francisco, California, United States of America.
7
Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, Georgia, United States of America.
8
Rwanda-Zambia HIV Research Group, Lusaka & Ndola, Zambia.
9
Rwanda-Zambia HIV Research Group, Project San Francisco, Kigali, Rwanda.
10
MRC/UVRI Uganda Research Unit on AIDS, Masaka & Entebbe, Uganda.
11
Centre for Geographic Medicine-Coast, Kenya Medical Research Institute, Kilifi, Kenya.
12
Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
13
Kenya AIDS Vaccine Initiative, Nairobi, Kenya.
14
The Aurum Institute, Parktown, Johannesburg, South Africa.
15
Desmond Tutu HIV Center, University of Cape Town, Cape Town, South Africa.
16
University of Alabama Birmingham, Department of Epidemiology and Department of Medicine, Birmingham, Alabama, United States of America.
17
IAVI Human Immunology Laboratory, Imperial College of Science Technology and Medicine, Chelsea & Westminster Hospital, London, United Kingdom.
18
Monogram Biosciences, Laboratory Corporation of America® Holdings, San Francisco California, United States of America.
19
Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), La Jolla, California, United States of America.
20
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America.

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.

PMID:
26766578
PMCID:
PMC4713061
DOI:
10.1371/journal.ppat.1005369
[Indexed for MEDLINE]
Free PMC Article

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