Difficult-to-neutralize global HIV-1 isolates are neutralized by antibodies targeting open envelope conformations

Qifeng Han, Julia A. Jones, Nathan I. Nicely, Rachel K. Reed, Xiaoying Shen, Katayoun Mansouri, Mark Louder, Ashley M. Trama, S. Munir Alam, Robert J. Edwards, Mattia Bonsignori, Georgia D. Tomaras, Bette Korber, David C. Montefiori, John R. Mascola, Michael S. Seaman, Barton F. Haynes () and Kevin O. Saunders ()
Additional contact information
Qifeng Han: Duke University Medical Center
Julia A. Jones: Duke University Medical Center
Nathan I. Nicely: Duke University Medical Center
Rachel K. Reed: Duke University Medical Center
Xiaoying Shen: Duke University Medical Center
Katayoun Mansouri: Duke University Medical Center
Mark Louder: National Instiftute of Allergy and Infectious Diseases (NIAID), NIH
Ashley M. Trama: Duke University Medical Center
S. Munir Alam: Duke University Medical Center
Robert J. Edwards: Duke University Medical Center
Mattia Bonsignori: Duke University Medical Center
Georgia D. Tomaras: Duke University Medical Center
Bette Korber: Los Alamos National Laboratory
David C. Montefiori: Duke University Medical Center
John R. Mascola: National Instiftute of Allergy and Infectious Diseases (NIAID), NIH
Michael S. Seaman: Israel Deaconess Medical Center
Barton F. Haynes: Duke University Medical Center
Kevin O. Saunders: Duke University Medical Center

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract The HIV-1 envelope (Env) is the target for neutralizing antibodies and exists on the surface of virions in open or closed conformations. Difficult-to-neutralize viruses (tier 2) express Env in a closed conformation antigenic for broadly neutralizing antibodies (bnAbs) but not for third variable region (V3) antibodies. Here we show that select V3 macaque antibodies elicited by Env vaccination can neutralize 26% of otherwise tier 2 HIV-1 isolates in standardized virus panels. The V3 antibodies only bound to Env in its open conformation. Thus, Envs on tier 2 viruses sample a state where the V3 loop is not in its closed conformation position. Envelope second variable region length, glycosylation sites and V3 amino acids were signatures of neutralization sensitivity. This study determined that open conformations of Env with V3 exposed are present on a subset of otherwise neutralization-resistant virions, therefore neutralization of tier 2 HIV-1 does not always indicate bnAb induction.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-10899-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10899-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-10899-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().