eprintid: 10145983 rev_number: 6 eprint_status: archive userid: 699 dir: disk0/10/14/59/83 datestamp: 2022-03-31 11:56:15 lastmod: 2022-03-31 11:56:15 status_changed: 2022-03-31 11:56:15 type: article metadata_visibility: show sword_depositor: 699 creators_name: Granger, Luke A creators_name: Huettner, Isabella creators_name: Debeljak, Franka creators_name: Kaleebu, Pontiano creators_name: Schechter, Mauro creators_name: Tambussi, Giuseppe creators_name: Weber, Jonathan creators_name: Miro, Jose M creators_name: Phillips, Rodney creators_name: Babiker, Abdel creators_name: Cooper, David A creators_name: Fisher, Martin creators_name: Ramjee, Gita creators_name: Fidler, Sarah creators_name: Frater, John creators_name: Fox, Julie creators_name: Doores, Katie J title: Broadly neutralizing antibody responses in the longitudinal primary HIV-1 infection Short Pulse Anti-Retroviral Therapy at Seroconversion cohort ispublished: pub divisions: UCL divisions: J38 divisions: D65 divisions: B02 keywords: Science & Technology, Life Sciences & Biomedicine, Immunology, Infectious Diseases, Virology, broadly neutralizing antibody, HIV-1, longitudinal, vaccine, IMMUNODEFICIENCY-VIRUS TYPE-1, MUCOSAL SHIV CHALLENGE, POTENT NEUTRALIZATION, INITIATION, SITE, VULNERABILITY, PREVALENCE, MATURATION, PROTECTION, BINDING note: © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. abstract: 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. date: 2021-11-01 date_type: published publisher: LIPPINCOTT WILLIAMS & WILKINS official_url: https://doi.org/10.1097/QAD.0000000000002988 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1872924 doi: 10.1097/QAD.0000000000002988 medium: Print pii: 00002030-900000000-96373 lyricists_name: Babiker, Abdel lyricists_id: ABABI41 actors_name: Payne, Roxanne actors_id: RPAYN74 actors_role: owner funding_acknowledgements: 069598/Z/02/Z [Wellcome]; 681137 [European Union's Horizon 2020 Research and Innovation program]; MR/K024426/1 [Medical Research Council (MRC)]; M686 [Rosetrees Trust]; [Fondation Dormeur, Vaduz]; [National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's andSt Thomas' NHS Foundation Trust and King's College London]; [NIHR Clinical Research Facility]; [King's Bioscience Institute]; [Guy's and St Thomas' Charity Prize Ph.D. Programme in Biomedical and Translational Science]; [Institut d'Investigacions Biome` diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain] full_text_status: public publication: AIDS volume: 35 number: 13 pagerange: 2073-2084 pages: 12 event_location: England issn: 0269-9370 citation: Granger, Luke A; Huettner, Isabella; Debeljak, Franka; Kaleebu, Pontiano; Schechter, Mauro; Tambussi, Giuseppe; Weber, Jonathan; ... Doores, Katie J; + view all <#> Granger, Luke A; Huettner, Isabella; Debeljak, Franka; Kaleebu, Pontiano; Schechter, Mauro; Tambussi, Giuseppe; Weber, Jonathan; Miro, Jose M; Phillips, Rodney; Babiker, Abdel; Cooper, David A; Fisher, Martin; Ramjee, Gita; Fidler, Sarah; Frater, John; Fox, Julie; Doores, Katie J; - view fewer <#> (2021) Broadly neutralizing antibody responses in the longitudinal primary HIV-1 infection Short Pulse Anti-Retroviral Therapy at Seroconversion cohort. AIDS , 35 (13) pp. 2073-2084. 10.1097/QAD.0000000000002988 <https://doi.org/10.1097/QAD.0000000000002988>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10145983/1/Broadly%20neutralizing%20antibody%20responses%20in%20the%20longitudinal%20primary%20HIV-1%20infection%20Short%20Pulse%20Anti-Retroviral%20Therapy%20at%20S.pdf