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

Publication date: 20 June 2017
Source:Immunity, Volume 46, Issue 6
Author(s): Matthias Pauthner, Colin Havenar-Daughton, Devin Sok, Joseph P. Nkolola, Raiza Bastidas, Archana V. Boopathy, Diane G. Carnathan, Abishek Chandrashekar, Kimberly M. Cirelli, Christopher A. Cottrell, Alexey M. Eroshkin, Javier Guenaga, Kirti Kaushik, Daniel W. Kulp, Jinyan Liu, Laura E. McCoy, Aaron L. Oom, Gabriel Ozorowski, Kai W. Post, Shailendra K. Sharma, Jon M. Steichen, Steven W. de Taeye, Talar Tokatlian, Alba Torrents de la Peña, Salvatore T. Butera, Celia C. LaBranche, David C. Montefiori, Guido Silvestri, Ian A. Wilson, Darrell J. Irvine, Rogier W. Sanders, William R. Schief, Andrew B. Ward, Richard T. Wyatt, Dan H. Barouch, Shane Crotty, Dennis R. Burton
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.

Graphical abstract

Teaser

There is limited experience with recombinant Env trimer immunogens in nonhuman primates. Pauthner et al. compare multiple Env trimer designs and immunization strategies for generating HIV neutralizing antibodies. They identify protocols for rapid and consistent generation of tier 2 nAbs, providing a framework for future pre-clinical and clinical vaccine studies.


http://ift.tt/2sqEGJD