Increased immunogenicity of HIV-1 p24 and gp120 following immunization with gp120/p24 fusion protein vaccine expressing α-gal epitopes

Ussama M. Abdel-Motal, Shixia Wang, Amany Awad, Shan Lu, Kim Wigglesworth, Uri Galili

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Developing an effective HIV-1 vaccine will require strategies to enhance antigen presentation to the immune system. In a previous study we demonstrated a marked increase in immunogenicity of the highly glycosylated HIV-1 gp120 protein following enzymatic addition of α-gal epitopes to the carbohydrate chains. In the present study we determined whether gp120αgal can also serve as an effective platform for targeting other HIV-1 proteins to APC and thus increase immunogenicity of both proteins. For this purpose we produced a recombinant fusion protein between gp120 and the HIV-1 matrix p24 protein (gp120/p24). Multiple α-gal epitopes were synthesized enzymatically on the gp120 portion of the fusion protein to generate a gp120αgal/p24 vaccine. Immune responses to gp120αgal/p24 compared to gp120/p24 vaccine lacking α-gal epitopes were evaluated in α1,3galactosyltransferase knockout (KO) mice. These mice lack α-gal epitopes and, therefore, are capable of producing the anti-Gal antibody. T cell responses to p24, as assessed by ELISPOT and by CD8+ T cells intracellular staining assays for IFNγ, was on average 12- and 10-fold higher, respectively, in gp120αgal/p24 immunized mice than in mice immunized with gp120/p24. In addition, cellular and humoral immune responses against gp120 were higher by 10-30-fold in mice immunized with gp120αgal/p24 than in gp120/p24 immunized mice. Our data suggest that the α-gal epitopes on the gp120 portion of the fusion protein can significantly augment the immunogenicity of gp120, as well as that of the fused viral protein which lacks α-gal epitopes. This strategy of anti-Gal mediated targeting to APC may be used for production of effective HIV-1 vaccines comprised of various viral proteins fused to gp120.

Original languageEnglish
Pages (from-to)1758-1765
Number of pages8
JournalVaccine
Volume28
Issue number7
DOIs
Publication statusPublished - 17 Feb 2010

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Keywords

  • Alpha-gal epitopes
  • HIV
  • Immunogenicity
  • Vaccine

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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