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.

In order to evaluate the MT145K trimer as an immunogen able to activate V2-apex bnAb precursor B cells, we took advantage of the availability of V2-apex bnAb UCA H-chain-only knockin mice. We compared MT145K and MT145 trimers as immunogens. Following two immunizations, MT145K trimers reproducibly elicited Abs able to neutralize the autologous virus and a few V2-apex Ab-sensitive viruses whereas MT145 trimers failed to induce such nAbs. The specificities of the nAbs were dependent on the glycan at N160 and a lysine on strand C of the V2. Boosting with a cocktail of HIV Env trimers successfully recalled the V2-apex-specific nAb responses and generated some enhanced heterologous neutralization. Therefore, from studies in this mouse model, the MT145K trimer appears to be a promising immunogen to induce V2-apex bnAbs. However, further immune evaluation of MT145K vaccine strategies in animal models expressing bnAb-encoding B cell precursors at frequencies closer to those expected in humans will be important (Abbott et al., 2018; Lee et al., 2014; Osborn et al., 2013) .