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.

Next, we evaluated binding of the MT145K trimer and monomeric gp120 to a panel of mAbs by ELISA and BLI. Consistent with the neutralization results above, bnAbs to the V2-apex site showed robust binding to the MT145K trimer (Figures 4B, S6, and S7), but other bnAbs and nnAbs did not bind, except for a few mAbs that displayed very weak binding (Figures 4B, S6, and S7). PG9, 17b, and some of the linear V3-loop directed mAbs (2557, 3074, 3904, and 14e) ( Figures 4B and S6 ) displayed binding to the MT145K gp120 monomer. The results suggest that the sequence-dependent epitopes for some of the nonneutralizing V3-loop mAbs are present on monomeric MT145K gp120, but are obscured on the MT145K trimer, as indicated by the MT145K structure. Virus neutralization and trimer binding by mAbs is strongly correlated (p = 0.003), consistent with the notion that the MT145K soluble trimer adopts a native-like trimeric Env configuration and displays antigenic properties suitable for a vaccine immunogen.