HIV-1 neutralizing antibodies induced by native-like envelope trimers | Zendy

Rogier W. Sanders | Zendy; Marit J. van Gils | Zendy; Ronald Derking | Zendy; Devin Sok | Zendy; Thomas J. Ketas | Zendy; Judith A. Burger | Zendy; Gabriel Ozorowski | Zendy; Albert Cupo | Zendy; Cassandra A. Simonich | Zendy; Leslie Goo | Zendy; Heather Arendt | Zendy; Helen J. Kim | Zendy; Jeong Hyun Lee | Zendy; Pavel Pugach | Zendy; Melissa Williams | Zendy; Gargi Debnath | Zendy; Brian Moldt | Zendy; Mariëlle J. van Breemen | Zendy; Gözde Isik | Zendy; Max Medina-Ramírez | Zendy; Jaap Willem Back | Zendy; Wayne C. Koff | Zendy; JeanPhilippe Julien | Zendy; Eva G. Rakasz | Zendy; Michael S. Seaman | Zendy; Miklós Guttman | Zendy; Kelly K. Lee | Zendy; Per Johan Klasse | Zendy; Celia C. LaBranche | Zendy; William R. Schief | Zendy; Ian A. Wilson | Zendy; Julie Overbaugh | Zendy; Dennis R. Burton | Zendy; Andrew B. Ward | Zendy; David C. Montefiori | Zendy; Hansi J. Dean | Zendy; John P. Moore | Zendy

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

Author(s) -

Rogier W. Sanders,

Marit J. van Gils,

Ronald Derking,

Devin Sok,

Thomas J. Ketas,

Judith A. Burger,

Gabriel Ozorowski,

Albert Cupo,

Cassandra A. Simonich,

Leslie Goo,

Heather Arendt,

Helen J. Kim,

Jeong Hyun Lee,

Pavel Pugach,

Melissa Williams,

Gargi Debnath,

Brian Moldt,

Mariëlle J. van Breemen,

Gözde Isik,

Max Medina-Ramírez,

Jaap Willem Back,

Wayne C. Koff,

JeanPhilippe Julien,

Eva G. Rakasz,

Michael S. Seaman,

Miklós Guttman,

Kelly K. Lee,

Per Johan Klasse,

Celia C. LaBranche,

William R. Schief,

Ian A. Wilson,

Julie Overbaugh,

Dennis R. Burton,

Andrew B. Ward,

David C. Montefiori,

Hansi J. Dean,

John P. Moore

Publication year - 2015

Publication title -

science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.aac4223

Subject(s) - immunogen , epitope , antibody , virology , glycoprotein , biology , human immunodeficiency virus (hiv) , neutralizing antibody , aids vaccines , virus , immunology , genetics , monoclonal antibody , vaccine trial

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 bNAb

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