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dc.creatorLandais, E
dc.creatorHuang, X
dc.creatorHavenar-Daughton, C
dc.creatorMurrell, B
dc.creatorPrice, MA
dc.creatorWickramasinghe, L
dc.creatorRamos, A
dc.creatorBian, CB
dc.creatorSimek, M
dc.creatorAllen, S
dc.creatorKarita, E
dc.creatorKilembe, W
dc.creatorLakhi, S
dc.creatorInambao, M
dc.creatorKamali, A
dc.creatorSanders, EJ
dc.creatorAnzala, O
dc.creatorEdward, V
dc.creatorBekker, LG
dc.creatorTang, J
dc.creatorGilmour, J
dc.creatorKosakovsky-Pond, SL
dc.creatorPhung, P
dc.creatorWrin, T
dc.creatorCrotty, S
dc.creatorGodzik, A
dc.creatorPoignard, P
dc.identifier.other26766578 (pubmed)
dc.description.abstract© 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.
dc.relation.haspartPLoS Pathogens
dc.relation.isreferencedbyPublic Library of Science (PLoS)
dc.rightsCC BY
dc.subjectAIDS Vaccines
dc.subjectAfrica South of the Sahara
dc.subjectAntibodies, Neutralizing
dc.subjectCohort Studies
dc.subjectEnzyme-Linked Immunosorbent Assay
dc.subjectEpitopes, B-Lymphocyte
dc.subjectHIV Antibodies
dc.subjectHIV Infections
dc.subjectLongitudinal Studies
dc.subjectMiddle Aged
dc.subjectYoung Adult
dc.subjectenv Gene Products, Human Immunodeficiency Virus
dc.titleBroadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort
dc.type.genreJournal Article
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact
dc.creator.orcidPond, Sergei L. Kosakovsky|0000-0003-4817-4029

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