HIV-1 neutralizing antibodies elicited in humans by a prefusion-stabilized envelope trimer form a reproducible class targeting fusion peptide

Author:

Wang, Shuishu

Matassoli, Flavio

Zhang, Baoshan

Liu, Tracy

Shen, Chen-Hsiang

Bylund, Tatsiana

Johnston, Timothy

Henry, Amy R

Teng, I-Ting

Tripathi, Prabhanshu

Becker, Jordan E

Changela, Anita

Chaudhary, Ridhi

Cheng, Cheng

Gaudinski, Martin

Gorman, Jason

Harris, Darcy R

Lee, Myungjin

Morano, Nicholas C

Novik, Laura

O'Dell, Sijy

Olia, Adam S

Parchment, Danealle K

Rawi, Reda

Roberts-Torres, Jesmine

Stephens,Tyler

Tsybovsky,Yaroslav

Wang, Danyi

Van Wazer, David J

Zhou, Tongqing

Doria-Rose, Nicole A

Koup, Richard A

Shapiro, Lawrence

Douek, Daniel C

McDermott, Adrian B

Kwong, Peter D
Author Address

Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA., Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Department of Biochemistry and Molecular Biophysics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA., Electron Microscopy Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA., Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA; Department of Biochemistry and Molecular Biophysics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA. Electronic address: pdkwong@nih.gov.,

Abstract:

Elicitation of antibodies that neutralize the tier-2 neutralization-resistant isolates that typify HIV-1 transmission has been a long-sought goal. Success with prefusion-stabilized envelope trimers eliciting autologous neutralizing antibodies has been reported in multiple vaccine-test species, though not in humans. To investigate elicitation of HIV-1 neutralizing antibodies in humans, here, we analyze B cells from a phase I clinical trial of the "DS-SOSIP"-stabilized envelope trimer from strain BG505, identifying two antibodies, N751-2C06.01 and N751-2C09.01 (named for donor-lineage.clone), that neutralize the autologous tier-2 strain, BG505. Though derived from distinct lineages, these antibodies form a reproducible antibody class that targets the HIV-1 fusion peptide. Both antibodies are highly strain specific, which we attribute to their partial recognition of a BG505-specific glycan hole and to their binding requirements for a few BG505-specific residues. Prefusion-stabilized envelope trimers can thus elicit autologous tier-2 neutralizing antibodies in humans, with initially identified neutralizing antibodies recognizing the fusion-peptide site of vulnerability. Published by Elsevier Inc.

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