Journal
SCIENCE
Volume 349, Issue 6244, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aac4223
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Funding
- NIH [P01 AI082362, R37 AI036082, R01 AI084817, R01 AI076105, P51OD011106]
- NIAID-NIH [HHSN27201100016C]
- Scripps CHAVI-ID [UM1 AI100663]
- Aids Fonds Netherlands [2011032, 2012041]
- Canadian Institutes of Health Research (CIHR) Fellowship
- Vidi grant from the Netherlands Organization for Scientific Research (NWO)
- Starting Investigator Grant from the European Research Council [ERC-StG-2011-280829-SHEV]
- IAVI
- USAID
- Bill & Melinda Gates Foundation
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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.
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