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

TitleHIV-1 VACCINES. HIV-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 JHyun, 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 PJohan, LaBranche C, Schief WR, Wilson IA, Overbaugh J, Burton DR, Ward AB, Montefiori DC, Dean H, Moore JP
JournalScience
Volume349
Issue6244
Paginationaac4223
Date Published2015 Jul 10
ISSN1095-9203
KeywordsAIDS Vaccines, Animals, Antibodies, Neutralizing, Cross Reactions, env Gene Products, Human Immunodeficiency Virus, Epitopes, HIV Antibodies, HIV Infections, HIV-1, Humans, Macaca, Protein Engineering, Protein Multimerization, Rabbits, Recombinant Proteins
Abstract

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.

DOI10.1126/science.aac4223
Alternate JournalScience
PubMed ID26089353
PubMed Central IDPMC4498988
Grant ListUM1 AI100663 / AI / NIAID NIH HHS / United States
P30 CA015704 / CA / NCI NIH HHS / United States
R01 AI076105 / AI / NIAID NIH HHS / United States
R01 AI084817 / AI / NIAID NIH HHS / United States
R56 AI084817 / AI / NIAID NIH HHS / United States
R37 AI036082 / AI / NIAID NIH HHS / United States
/ / Canadian Institutes of Health Research / Canada
T32 GM007266 / GM / NIGMS NIH HHS / United States
P51 OD011106 / OD / NIH HHS / United States
P51OD011106 / OD / NIH HHS / United States
P01 AI082362 / AI / NIAID NIH HHS / United States
HHSN27201100016C / / PHS HHS / United States
280829 / / European Research Council / International