HIV-1 VACCINES. HIV-1 neutralizing antibodies induced by native-like envelope trimers.
A challenge for HIV-1 immunogen design is the difficulty of inducing neutralizing antibodies (NAbs) against neutralization-resistant (tier 2) viruses that dominate human transmissions. We show that a soluble recombinant HIV-1 envelope glycoprotein trimer that adopts a native conformation, BG505 SOSIP.664, induced NAbs potently against the sequence-matched tier 2 virus in rabbits and similar but weaker responses in macaques. The trimer also consistently induced cross-reactive NAbs against more sensitive (tier 1) viruses. Tier 2 NAbs recognized conformational epitopes that differed between animals and in some cases overlapped with those recognized by broadly neutralizing antibodies (bNAbs), whereas tier 1 responses targeted linear V3 epitopes. A second trimer, B41 SOSIP.664, also induced a strong autologous tier 2 NAb response in rabbits. Thus, native-like trimers represent a promising starting point for the development of HIV-1 vaccines aimed at inducing bNAbs.
Sanders, RW; van Gils, MJ; Derking, R; Sok, D; Ketas, TJ; Burger, JA; Ozorowski, G; Cupo, A; Simonich, C; Goo, L; Arendt, H; Kim, HJ; Lee, JH; Pugach, P; Williams, M; Debnath, G; Moldt, B; van Breemen, MJ; Isik, G; Medina-Ramírez, M; Back, JW; Koff, WC; Julien, J-P; Rakasz, EG; Seaman, MS; Guttman, M; Lee, KK; Klasse, PJ; LaBranche, C; Schief, WR; Wilson, IA; Overbaugh, J; Burton, DR; Ward, AB; Montefiori, DC; Dean, H; Moore, JP
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