Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort
Genre
Journal ArticleDate
2016-01-01Author
Landais, EHuang, X
Havenar-Daughton, C
Murrell, B
Price, MA
Wickramasinghe, L
Ramos, A
Bian, CB
Simek, M
Allen, S
Karita, E
Kilembe, W
Lakhi, S
Inambao, M
Kamali, A
Sanders, EJ
Anzala, O
Edward, V
Bekker, LG
Tang, J
Gilmour, J
Kosakovsky-Pond, SL
Phung, P
Wrin, T
Crotty, S
Godzik, A
Poignard, P
Subject
AIDS VaccinesAdult
Africa South of the Sahara
Antibodies, Neutralizing
Cohort Studies
Enzyme-Linked Immunosorbent Assay
Epitopes, B-Lymphocyte
Female
HIV Antibodies
HIV Infections
Humans
Longitudinal Studies
Male
Middle Aged
Young Adult
env Gene Products, Human Immunodeficiency Virus
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http://hdl.handle.net/20.500.12613/5170
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10.1371/journal.ppat.1005369Abstract
© 2016 Landais et al. 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.Citation to related work
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http://dx.doi.org/10.34944/dspace/5152