HIV-1 neutralizing antibodies induced by native-like envelope trimers.

TitleHIV-1 neutralizing antibodies induced by native-like envelope trimers.
Publication TypeJournal Article
Year of Publication2015
AuthorsSanders 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 J H, Pugach P, Williams M, Debnath G, Moldt B, van Breemen MJ, Isik G, Medina-Ramírez M, Back JWillem, Koff WC, Julien J-P, Rakasz EG, Seaman MS, Guttman M, Lee KK, Klasse P J, LaBranche C, Schief WR, Wilson IA, Overbaugh J, Burton DR, Ward AB, Montefiori DC, Dean H, Moore JP
JournalScience
Date Published07/10/2015
ISSN1095-9203
Abstract

A challenge for HIV-1 immunogen design is 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 developing HIV-1 vaccines aimed at inducing bNAbs.

DOI10.1126/science.aac4223
Alternate JournalScience
PubMed ID26089353
Grant ListP01 AI082362 / AI / NIAID NIH HHS / United States
R56 AI084817 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
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