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.

(legend on next page) KI-mouse model expresses the pre-rearranged heavy chain (V H DDJ H ) of the CH01 V2-apex bnAb UCA paired with wildtype (WT) mouse light chains. We immunized two groups of five CH01 UCA heavy chain (HC)-only KI mice, each with two repeated doses (at weeks 0 and 4) of the MT145-WT or MT145K trimer ( Figure 6A ). To track the development of Ab responses, we performed ELISA assays of the pre-bleed, 2-week (day 14) post-prime (Bleed #1) and 2-week post boost-1 (day 42) (Bleed #2) serum samples with MT145K SOSIP trimer protein and its N160-glycan-eliminated variant (MT145K N160K) ( Figure 6B ). The N160 glycan is a critical component of the V2-apex bnAb epitope McLellan et al., 2011; Pancera et al., 2013; Walker et al., 2009 ). The pre-bleed serum samples in both immunization groups exhibited weak binding activity with the MT145K trimer that was dependent on the N160 glycan, consistent with the presence of CH01 UCA Abs that do show some binding to the MT145K trimer, as described above ( Figure 6B ).