Skip to main content

Immune focusing and enhanced neutralization induced by HIV-1 gp140 chemical cross-linking.

Publication ,  Journal Article
Schiffner, T; Kong, L; Duncan, CJA; Back, JW; Benschop, JJ; Shen, X; Huang, PS; Stewart-Jones, GB; DeStefano, J; Seaman, MS; Tomaras, GD ...
Published in: J Virol
September 2013

Experimental vaccine antigens based upon the HIV-1 envelope glycoproteins (Env) have failed to induce neutralizing antibodies (NAbs) against the majority of circulating viral strains as a result of antibody evasion mechanisms, including amino acid variability and conformational instability. A potential vaccine design strategy is to stabilize Env, thereby focusing antibody responses on constitutively exposed, conserved surfaces, such as the CD4 binding site (CD4bs). Here, we show that a largely trimeric form of soluble Env can be stably cross-linked with glutaraldehyde (GLA) without global modification of antigenicity. Cross-linking largely conserved binding of all potent broadly neutralizing antibodies (bNAbs) tested, including CD4bs-specific VRC01 and HJ16, but reduced binding of several non- or weakly neutralizing antibodies and soluble CD4 (sCD4). Adjuvanted administration of cross-linked or unmodified gp140 to rabbits generated indistinguishable total gp140-specific serum IgG binding titers. However, sera from animals receiving cross-linked gp140 showed significantly increased CD4bs-specific antibody binding compared to animals receiving unmodified gp140. Moreover, peptide mapping of sera from animals receiving cross-linked gp140 revealed increased binding to gp120 C1 and V1V2 regions. Finally, neutralization titers were significantly elevated in sera from animals receiving cross-linked gp140 rather than unmodified gp140. We conclude that cross-linking favors antigen stability, imparts antigenic modifications that selectively refocus antibody specificity and improves induction of NAbs, and might be a useful strategy for future vaccine design.

Duke Scholars

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

September 2013

Volume

87

Issue

18

Start / End Page

10163 / 10172

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Virology
  • Rabbits
  • HIV Antigens
  • HIV Antibodies
  • Cross-Linking Reagents
  • Antibodies, Neutralizing
  • Animals
  • Adjuvants, Immunologic
  • AIDS Vaccines
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Schiffner, T., Kong, L., Duncan, C. J. A., Back, J. W., Benschop, J. J., Shen, X., … Sattentau, Q. J. (2013). Immune focusing and enhanced neutralization induced by HIV-1 gp140 chemical cross-linking. J Virol, 87(18), 10163–10172. https://doi.org/10.1128/JVI.01161-13
Schiffner, T., L. Kong, C. J. A. Duncan, J. W. Back, J. J. Benschop, X. Shen, P. S. Huang, et al. “Immune focusing and enhanced neutralization induced by HIV-1 gp140 chemical cross-linking.J Virol 87, no. 18 (September 2013): 10163–72. https://doi.org/10.1128/JVI.01161-13.
Schiffner T, Kong L, Duncan CJA, Back JW, Benschop JJ, Shen X, et al. Immune focusing and enhanced neutralization induced by HIV-1 gp140 chemical cross-linking. J Virol. 2013 Sep;87(18):10163–72.
Schiffner, T., et al. “Immune focusing and enhanced neutralization induced by HIV-1 gp140 chemical cross-linking.J Virol, vol. 87, no. 18, Sept. 2013, pp. 10163–72. Pubmed, doi:10.1128/JVI.01161-13.
Schiffner T, Kong L, Duncan CJA, Back JW, Benschop JJ, Shen X, Huang PS, Stewart-Jones GB, DeStefano J, Seaman MS, Tomaras GD, Montefiori DC, Schief WR, Sattentau QJ. Immune focusing and enhanced neutralization induced by HIV-1 gp140 chemical cross-linking. J Virol. 2013 Sep;87(18):10163–10172.

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

September 2013

Volume

87

Issue

18

Start / End Page

10163 / 10172

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Virology
  • Rabbits
  • HIV Antigens
  • HIV Antibodies
  • Cross-Linking Reagents
  • Antibodies, Neutralizing
  • Animals
  • Adjuvants, Immunologic
  • AIDS Vaccines