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Recognition of synthetic glycopeptides by HIV-1 broadly neutralizing antibodies and their unmutated ancestors.

Publication ,  Journal Article
Alam, SM; Dennison, SM; Aussedat, B; Vohra, Y; Park, PK; Fernández-Tejada, A; Stewart, S; Jaeger, FH; Anasti, K; Blinn, JH; Kepler, TB ...
Published in: Proc Natl Acad Sci U S A
November 5, 2013

Current HIV-1 vaccines elicit strain-specific neutralizing antibodies. Broadly neutralizing antibodies (BnAbs) are not induced by current vaccines, but are found in plasma in ∼20% of HIV-1-infected individuals after several years of infection. One strategy for induction of unfavored antibody responses is to produce homogeneous immunogens that selectively express BnAb epitopes but minimally express dominant strain-specific epitopes. Here we report that synthetic, homogeneously glycosylated peptides that bind avidly to variable loop 1/2 (V1V2) BnAbs PG9 and CH01 bind minimally to strain-specific neutralizing V2 antibodies that are targeted to the same envelope polypeptide site. Both oligomannose derivatization and conformational stabilization by disulfide-linked dimer formation of synthetic V1V2 peptides were required for strong binding of V1V2 BnAbs. An HIV-1 vaccine should target BnAb unmutated common ancestor (UCA) B-cell receptors of naïve B cells, but to date no HIV-1 envelope constructs have been found that bind to the UCA of V1V2 BnAb PG9. We demonstrate herein that V1V2 glycopeptide dimers bearing Man5GlcNAc2 glycan units bind with apparent nanomolar affinities to UCAs of V1V2 BnAbs PG9 and CH01 and with micromolar affinity to the UCA of a V2 strain-specific antibody. The higher-affinity binding of these V1V2 glycopeptides to BnAbs and their UCAs renders these glycopeptide constructs particularly attractive immunogens for targeting subdominant HIV-1 envelope V1V2-neutralizing antibody-producing B cells.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

November 5, 2013

Volume

110

Issue

45

Start / End Page

18214 / 18219

Location

United States

Related Subject Headings

  • Surface Plasmon Resonance
  • Receptors, Antigen, B-Cell
  • Protein Binding
  • HIV-1
  • Glycopeptides
  • Electrophoresis, Polyacrylamide Gel
  • Dimerization
  • Antibodies, Neutralizing
  • AIDS Vaccines
 

Citation

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MLA
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Alam, S. M., Dennison, S. M., Aussedat, B., Vohra, Y., Park, P. K., Fernández-Tejada, A., … Haynes, B. F. (2013). Recognition of synthetic glycopeptides by HIV-1 broadly neutralizing antibodies and their unmutated ancestors. Proc Natl Acad Sci U S A, 110(45), 18214–18219. https://doi.org/10.1073/pnas.1317855110
Alam, S Munir, S Moses Dennison, Baptiste Aussedat, Yusuf Vohra, Peter K. Park, Alberto Fernández-Tejada, Shelley Stewart, et al. “Recognition of synthetic glycopeptides by HIV-1 broadly neutralizing antibodies and their unmutated ancestors.Proc Natl Acad Sci U S A 110, no. 45 (November 5, 2013): 18214–19. https://doi.org/10.1073/pnas.1317855110.
Alam SM, Dennison SM, Aussedat B, Vohra Y, Park PK, Fernández-Tejada A, et al. Recognition of synthetic glycopeptides by HIV-1 broadly neutralizing antibodies and their unmutated ancestors. Proc Natl Acad Sci U S A. 2013 Nov 5;110(45):18214–9.
Alam, S. Munir, et al. “Recognition of synthetic glycopeptides by HIV-1 broadly neutralizing antibodies and their unmutated ancestors.Proc Natl Acad Sci U S A, vol. 110, no. 45, Nov. 2013, pp. 18214–19. Pubmed, doi:10.1073/pnas.1317855110.
Alam SM, Dennison SM, Aussedat B, Vohra Y, Park PK, Fernández-Tejada A, Stewart S, Jaeger FH, Anasti K, Blinn JH, Kepler TB, Bonsignori M, Liao H-X, Sodroski JG, Danishefsky SJ, Haynes BF. Recognition of synthetic glycopeptides by HIV-1 broadly neutralizing antibodies and their unmutated ancestors. Proc Natl Acad Sci U S A. 2013 Nov 5;110(45):18214–18219.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

November 5, 2013

Volume

110

Issue

45

Start / End Page

18214 / 18219

Location

United States

Related Subject Headings

  • Surface Plasmon Resonance
  • Receptors, Antigen, B-Cell
  • Protein Binding
  • HIV-1
  • Glycopeptides
  • Electrophoresis, Polyacrylamide Gel
  • Dimerization
  • Antibodies, Neutralizing
  • AIDS Vaccines