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

Publication ,  Journal Article
Han, Q; Jones, JA; Nicely, NI; Reed, RK; Shen, X; Mansouri, K; Louder, M; Trama, AM; Alam, SM; Edwards, RJ; Bonsignori, M; Tomaras, GD ...
Published in: Nat Commun
July 1, 2019

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.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

July 1, 2019

Volume

10

Issue

1

Start / End Page

2898

Location

England

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Protein Conformation
  • Neutralization Tests
  • Macaca mulatta
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Antibodies
  • Glycosylation
  • Antibodies, Neutralizing
 

Citation

APA
Chicago
ICMJE
MLA
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Han, Q., Jones, J. A., Nicely, N. I., Reed, R. K., Shen, X., Mansouri, K., … Saunders, K. O. (2019). Difficult-to-neutralize global HIV-1 isolates are neutralized by antibodies targeting open envelope conformations. Nat Commun, 10(1), 2898. https://doi.org/10.1038/s41467-019-10899-2
Han, Qifeng, Julia A. Jones, Nathan I. Nicely, Rachel K. Reed, Xiaoying Shen, Katayoun Mansouri, Mark Louder, et al. “Difficult-to-neutralize global HIV-1 isolates are neutralized by antibodies targeting open envelope conformations.Nat Commun 10, no. 1 (July 1, 2019): 2898. https://doi.org/10.1038/s41467-019-10899-2.
Han Q, Jones JA, Nicely NI, Reed RK, Shen X, Mansouri K, et al. Difficult-to-neutralize global HIV-1 isolates are neutralized by antibodies targeting open envelope conformations. Nat Commun. 2019 Jul 1;10(1):2898.
Han, Qifeng, et al. “Difficult-to-neutralize global HIV-1 isolates are neutralized by antibodies targeting open envelope conformations.Nat Commun, vol. 10, no. 1, July 2019, p. 2898. Pubmed, doi:10.1038/s41467-019-10899-2.
Han Q, Jones JA, Nicely NI, Reed RK, Shen X, Mansouri K, Louder M, Trama AM, Alam SM, Edwards RJ, Bonsignori M, Tomaras GD, Korber B, Montefiori DC, Mascola JR, Seaman MS, Haynes BF, Saunders KO. Difficult-to-neutralize global HIV-1 isolates are neutralized by antibodies targeting open envelope conformations. Nat Commun. 2019 Jul 1;10(1):2898.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

July 1, 2019

Volume

10

Issue

1

Start / End Page

2898

Location

England

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Protein Conformation
  • Neutralization Tests
  • Macaca mulatta
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Antibodies
  • Glycosylation
  • Antibodies, Neutralizing