Pauthner, M;
Havenar-Daughton, C;
Sok, D;
Nkolola, JP;
Bastidas, R;
Boopathy, AV;
Carnathan, DG;
... Burton, DR; + view all
(2017)
Elicitation of Robust Tier 2 Neutralizing Antibody Responses in Nonhuman Primates by HIV Envelope Trimer Immunization Using Optimized Approaches.
Immunity
, 46
(6)
1073-1088.e6.
10.1016/j.immuni.2017.05.007.
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Abstract
The development of stabilized recombinant HIV envelope trimers that mimic the virion surface molecule has increased enthusiasm for a neutralizing antibody (nAb)-based HIV vaccine. However, there is limited experience with recombinant trimers as immunogens in nonhuman primates, which are typically used as a model for humans. Here, we tested multiple immunogens and immunization strategies head-to-head to determine their impact on the quantity, quality, and kinetics of autologous tier 2 nAb development. A bilateral, adjuvanted, subcutaneous immunization protocol induced reproducible tier 2 nAb responses after only two immunizations 8 weeks apart, and these were further enhanced by a third immunization with BG505 SOSIP trimer. We identified immunogens that minimized non-neutralizing V3 responses and demonstrated that continuous immunogen delivery could enhance nAb responses. nAb responses were strongly associated with germinal center reactions, as assessed by lymph node fine needle aspiration. This study provides a framework for preclinical and clinical vaccine studies targeting nAb elicitation.
| Type: | Article |
|---|---|
| Title: | Elicitation of Robust Tier 2 Neutralizing Antibody Responses in Nonhuman Primates by HIV Envelope Trimer Immunization Using Optimized Approaches |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.immuni.2017.05.007 |
| Publisher version: | https://doi.org/10.1016/j.immuni.2017.05.007 |
| Language: | English |
| Additional information: | © 2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | HIV vaccine; nonhuman primates; rhesus macaques; BG505; SOSIP; NFL; GC B cells; protein design; Tfh cells; germinal centers |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10022838 |
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