Broadly neutralizing antibody responses in the longitudinal primary HIV-1 infection Short Pulse Anti-Retroviral Therapy at Seroconversion cohort

TY - JOUR

T1 - Broadly neutralizing antibody responses in the longitudinal primary HIV-1 infection Short Pulse Anti-Retroviral Therapy at Seroconversion cohort

AU - Granger, Luke A.

AU - Huettner, Isabella

AU - Debeljak, Franka

AU - Kaleebu, Pontiano

AU - Schechter, Mauro

AU - Tambussi, Giuseppe

AU - Weber, Jonathan

AU - Miro, Jose M.

AU - Phillips, Rodney

AU - Babiker, Abdel

AU - Cooper, David A.

AU - Fisher, Martin

AU - Ramjee, Gita

AU - Fidler, Sarah

AU - Frater, John

AU - Fox, Julie

AU - Doores, Katie J.

N1 - Publisher Copyright: Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

PY - 2021/11/1

Y1 - 2021/11/1

N2 - OBJECTIVE: Development 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 METHODS: Longitudinal 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. RESULTS: In 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. CONCLUSION: This study highlights the SPARTAC cohort as an important resource for more in-depth analysis of bnAb developmental pathways.

AB - OBJECTIVE: Development 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 METHODS: Longitudinal 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. RESULTS: In 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. CONCLUSION: This study highlights the SPARTAC cohort as an important resource for more in-depth analysis of bnAb developmental pathways.

UR - http://www.scopus.com/inward/record.url?scp=85118096383&partnerID=8YFLogxK

U2 - 10.1097/QAD.0000000000002988

DO - 10.1097/QAD.0000000000002988

M3 - Article

C2 - 34127581

AN - SCOPUS:85118096383

SN - 0269-9370

VL - 35

SP - 2073

EP - 2084

JO - AIDS (London, England)

JF - AIDS (London, England)

IS - 13

ER -