Abstract
SummaryThe 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.
Highlights
Successful vaccines to viral pathogens rely heavily on the induction of neutralizing antibody responses for host protection (Plotkin, 2010)
We focused on the analysis of tier 2 neutralizing antibody (nAb) and nonneutralizing Ab responses, together with germinal center (GC) responses, in the draining lymph nodes (LNs)
Induction of Potent nAb Titers after Two Immunizations with Env Trimers To try to improve the consistency and magnitude of BG505 SOSIP.664 nAb responses, we evaluated a modified immunization protocol designed to boost and prolong GC activity between immunizations
Summary
Successful vaccines to viral pathogens rely heavily on the induction of neutralizing antibody (nAb) responses for host protection (Plotkin, 2010). The induction of nAbs to circulating HIV (so-called tier 2 viruses) through immunization has proven very. Immunity 46, 1073–1088, June 20, 2017 a 2017 The Authors. Week: -2 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 ... Immunization Blood draw LN Fine Needle Aspirate Weeks LOD. Week: -2 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 ... 24 25 26 27 28 ... 32 ... 44
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