The Chimpanzee SIV Envelope Trimer: Structure and Deployment as an HIV Vaccine Template

Andrabi, Raiees; Pallesen, Jesper; Allen, Joel D.; Song, Ge; Zhang, Jinsong; de Val, Natalia; Gegg, Gavin; Porter, Katelyn; Su, Ching-Yao; Pauthner, Matthias; Newman, Amanda; Bouton-Verville, Hilary; Garces, Fernando; Wilson, Ian A.; Crispin, Max; Hahn, Beatrice H.; Haynes, Barton F.; Verkoczy, Laurent; Ward, Andrew B.; Burton, Dennis R.

Of note, among the major HIV Env bnAb specificities, which include V2-apex, V3-N332, CD4bs, and the gp120-41 interface, the V2-apex is the only bnAb site that consistently exhibits cross-group neutralizing activity with virus Envs derived from HIV groups M, N, O, and P (Braibant et al., 2013; Morgand et al., 2016) . Furthermore, V2-apex bnAbs display cross-neutralizing activity with the simian immunodeficiency virus (SIV) isolates that infect chimpanzees (SIVcpzPtt [Pan troglodytes troglodytes], SIVcpzPts [Pan troglodytes schweinfurthii]) and gorillas (SIVgor) (Barbian et al., 2015) . The retention of the V2-apex bnAb epitope at the time of species crossover from chimpanzees to humans highlights the biological significance of this region and here we sought to design a trimer based on the SIVcpzPtt Env sequence that could potentially help guide an immunofocused response to the HIV V2-apex bnAb site. We hypothesized that an SIVcpzPttbased trimer will not only assist in specifically enriching V2-apexspecific B cells but also, owing to V2-apex species cross-conservation, could assist in guiding a V2-focused nAb response when coupled with HIV trimers in a sequential prime-boost immunization strategy. In such an immunization scheme, the overall Env backbone sequence diversity in combination with conservation of the V2-apex bnAb epitope in sequentially administered immunogens is likely to reduce germinal center competition for V2apex-specific B cells (Havenar-Daughton et al., 2017; Tas et al., 2016; Wang et al., 2015) . Such a scheme could not only favor a B cell recall response to the V2-apex bnAb epitope but also reduce off-target Env-specific responses.