Elicitation of Robust Tier 2 Neutralizing Antibody Responses in Nonhuman Primates by HIV Envelope Trimer Immunization Using Optimized Approaches.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Pauthner, M; Havenar-Daughton, C; Sok, D; Nkolola, JP; Bastidas, R; Boopathy, AV; Carnathan, DG; Chandrashekar, A; Cirelli, KM; Cottrell, CA; Eroshkin, AM; Guenaga, J; Kaushik, K; Kulp, DW; Liu, J; McCoy, LE; Oom, AL; Ozorowski, G; Post, KW; Sharma, SK; Steichen, JM; de Taeye, SW; Tokatlian, T; Torrents de la Peña, A; Butera, ST; LaBranche, CC; Montefiori, DC; Silvestri, G; Wilson, IA; Irvine, DJ; Sanders, RW; Schief, WR; Ward, AB; Wyatt, RT; Barouch, DH; Crotty, S; Burton, DR

Published Date

  • June 2017

Published In

Volume / Issue

  • 46 / 6

Start / End Page

  • 1073 - 1088.e6

PubMed ID

  • 28636956

Pubmed Central ID

  • 28636956

Electronic International Standard Serial Number (EISSN)

  • 1097-4180

International Standard Serial Number (ISSN)

  • 1074-7613

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2017.05.007

Language

  • eng