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ObjectiveDevelopment of immunogens that elicit an anti-HIV-1 broadly neutralizing antibody (bnAb) response will be a key step in the development of an effective HIV-1 vaccine. Although HIV-1 bnAb epitopes have been identified and mechanisms of action studied, current HIV-1 envelope-based immunogens do not elicit HIV-1 bnAbs in humans or animal models. A better understanding of how HIV-1 bnAbs arise during infection and the clinical factors associated with bnAb development may be critical for HIV-1 immunogen design efforts.Design and methodsLongitudinal plasma samples from the treatment-naive control arm of the Short Pulse Anti-Retroviral Therapy at Seroconversion (SPARTAC) primary HIV-1 infection cohort were used in an HIV-1 pseudotype neutralization assay to measure the neutralization breadth, potency and specificity of bnAb responses over time.ResultsIn the SPARTAC cohort, development of plasma neutralization breadth and potency correlates with duration of HIV infection and high viral loads, and typically takes 3-4 years to arise. bnAb activity was mostly directed to one or two bnAb epitopes per donor and more than 60% of donors with the highest plasma neutralization having bnAbs targeted towards glycan-dependent epitopes.ConclusionThis study highlights the SPARTAC cohort as an important resource for more in-depth analysis of bnAb developmental pathways.

Original publication

DOI

10.1097/qad.0000000000002988

Type

Journal article

Journal

AIDS (London, England)

Publication Date

11/2021

Volume

35

Pages

2073 - 2084

Addresses

Department of Infectious Diseases, King's College London, Guy's Hospital, Great Maze Pond, London, UK.

Keywords

Animals, Humans, HIV-1, HIV Infections, HIV Antibodies, Antibodies, Neutralizing, Seroconversion, Broadly Neutralizing Antibodies