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.

Vaccination has taken advantage of related viruses from different species, beginning with the use of cowpox as a smallpox vaccine (Riedel, 2005) . HIV is too variable and has too many evasion mechanisms for such an approach applied directly to work effectively. Nevertheless, there are HIV-related viruses that have the potential to be exploited in some form in vaccine design. Indeed, the HIV pandemic is believed to have arisen because of a crossspecies virus transmission from chimpanzees to humans during the period from 1910 to 1930 (Korber et al., 2000; Sharp and Hahn, 2011; Worobey et al., 2008) . The HIV and chimpanzee SIV Envs, the target of potentially protective neutralizing antibodies, display about 60% sequence conservation at the amino-acid level. Importantly, HIV V2-apex bnAbs have been shown to neutralize certain chimpanzee SIV isolates, including the SIVcpzPtt isolate MT145, suggesting cross-species conservation of this epitope (Barbian et al., 2015) . Accordingly, we generated a chimpanzee SIV Env trimer (MT145 SOSIP) and showed that it bound HIV V2-apex bnAbs. We then engineered it to bind to germline-reverted V2-apex bnAbs (MT145K SOSIP) so that it might be useful in activating V2-apex precursors.