@article{d9ed0900e0734f738673b68134c78b9a,
title = "Fine-mapping the immunodominant antibody epitopes on consensus sequence-based HIV-1 envelope trimer vaccine candidates",
abstract = "The HIV-1 envelope glycoprotein (Env) trimer is the key target for vaccines aimed at inducing neutralizing antibodies (NAbs) against HIV-1. The clinical candidate immunogen ConM SOSIP.v7 is a stabilized native-like HIV-1 Env trimer based on an artificial consensus sequence of all HIV-1 isolates in group M. In preclinical studies ConM SOSIP.v7 trimers induced strong autologous NAb responses in non-human primates (NHPs). To fine-map these responses, we isolated monoclonal antibodies (mAbs) from six cynomolgus macaques that were immunized three times with ConM SOSIP.v7 protein and boosted twice with the closely related ConSOSL.UFO.664 immunogen. A total of 40 ConM and/or ConS-specific mAbs were isolated, of which 18 were retrieved after the three ConM SOSIP.v7 immunizations and 22 after the two immunizations with ConSOSL.UFO.664. 22 mAbs (55%) neutralized the ConM and/or ConS virus. Cross-neutralization of ConS virus by approximately one-third of the mAbs was seen prior to ConSOSL.UFO.664 immunization, albeit with modest potency. Neutralizing antibodies predominantly targeted the V1 and V2 regions of the immunogens, with an apparent extension towards the V3 region. Thus, the V1V2V3 region is immunodominant in the potent NAb response elicited by two consensus sequence native-like HIV-1 Env immunogens. Immunization with these soluble consensus Env proteins also elicited non-neutralizing mAbs targeting the trimer base. These results inform the use and improvement of consensus-based trimer immunogens in combinatorial vaccine strategies.",
author = "Reiss, {E I M M} and {van Haaren}, {M M} and {van Schooten}, J and Claireaux, {M A F} and P Maisonnasse and A Antanasijevic and Allen, {J D} and I Bontjer and Torres, {J L} and W-H Lee and G Ozorowski and {V{\'a}zquez Bernat}, N and M Kaduk and Y Aldon and Burger, {J A} and H Chawla and A Aartse and M Tolazzi and H Gao and P Mundsperger and M Crispin and Montefiori, {D C} and {Karlsson Hedestam}, {G B} and G Scarlatti and Ward, {A B} and {Le Grand}, R and R Shattock and N Dereuddre-Bosquet and Sanders, {R W} and {van Gils}, {M J}",
note = "Funding Information: This work was supported by the European Union{\textquoteright}s Horizon 2020 research and innovation program EAVI2020 under grant agreement no. 681137, as well as the HIV Vaccine Research and Design (HIVRAD) program (P01 AI110657) (A.B.W. and R.W.S). Furthermore, this work was supported, in whole or in part, by the Collaboration for AIDS Vaccine Discovery (CAVD) grants OPP1115782, OPP1132237, INV-002022, funded by the Bill and Melinda Gates Foundation. Under the grant conditions of the Foundation, a Creative Commons Attribution 4.0 Generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission. R.W.S. is a recipient of a Vici fellowship from the Netherlands Organization for Scientific Research (NWO). M.J.v.G. is supported by an amfAR Mathilde Krim Fellowships in Basic Biomedical Research grant number 109514-61-RKVA and the 2017 AMC Fellowship. Al.A. is supported by amfAR Mathilde Krim Fellowship in Biomedical Research no. 110182-69-RKVA. The neutralization assays performed at Duke University were supported by NIAID-NIH (HHSN272201800004C). The Infectious Disease Models and Innovative Therapies research infrastructure (IDMIT) is supported by the “Program Investissements d{\textquoteright}Avenir” (PIA), managed by the ANR under references ANR-11-INBS-0008. The glycopeptide analysis was supported by the CAVD grant INV-008352/OPP1153692 funded by the Bill and Melinda Gates Foundation (M.C.). We are grateful to the staff of IDMIT, particularly to C. Joubert, R. Ho Tsong Fang, B. Delache, S. Langlois, E. Burban, M. Potier, N. Dhooge, J.-M. Robert, M. Barendi, J. Dinh, E. Guyon, S. Keyser and I. Mangeot. G.S., R.W.S, and M.J.v.G. received charitable donations from Fondation Dormeur, Vaduz, for instruments supporting the research of this study. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "https://doi.org/10.1038/s41541-022-00576-9",
language = "English",
volume = "7",
pages = "152",
journal = "npj Vaccines",
issn = "1476-0584",
publisher = "Expert Reviews Ltd.",
number = "1",
}