Increased immunogenicity of human immunodeficiency virus gp120 engineered to express Galα1-3Galβ1-4GlcNAc-R epitopes

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

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

The glycan shield comprised of multiple carbohydrate chains on the human immunodeficiency virus (HIV) envelope glycoprotein gp120 helps the virus to evade neutralizing antibodies. The present study describes a novel method for increasing immunogenicity of gp120 vaccine by enzymatic replacement of sialic acid on these carbohydrate chains with Galα1-3Galβ1-4GlcNAc-R (α-gal) epitopes. These epitopes are ligands for the natural anti-Gal antibody constituting ∼1% of immunoglobulin G in humans. We hypothesize that vaccination with gp120 expressing α-gal epitopes (gp120 αgal) results in in vivo formation of immune complexes with anti-Gal, which targets vaccines for effective uptake by antigen-presenting cells (APC), due to interaction between the Fc portion of the antibody and FCγ receptors on APC. This in turn results in effective transport of the vaccine to lymph nodes and effective processing and presentation of gp120 immunogenic peptides by APC for eliciting a strong anti-gp120 immune response. This hypothesis was tested in α-1,3-galactosyltransferase knockout mice, which produce anti-Gal. Mice immunized with gp120αgal1 produced anti-gp120 antibodies in titers that were >100-fold higher than those measured in mice immunized with comparable amounts of gp120 and effectively neutralized HIV. T-cell response, measured by ELISPOT, was much higher in mice immunized with gp120αgal than in mice immunized with gp120. It is suggested that gp120αgal can serve as a platform for anti-Gal-mediated targeting of additional vaccinating HIV proteins fused to gp120αgal, thereby creating effective prophylactic vaccines.

Original languageEnglish
Pages (from-to)6943-6951
Number of pages9
JournalJournal of Virology
Volume80
Issue number14
DOIs
Publication statusPublished - Jul 2006
Externally publishedYes

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Epitopes
Antigen-Presenting Cells
HIV
Vaccines
Anti-Idiotypic Antibodies
Carbohydrates
Human Immunodeficiency Virus Proteins
Galactosyltransferases
Enzyme-Linked Immunospot Assay
N-Acetylneuraminic Acid
Antigen-Antibody Complex
Neutralizing Antibodies
Knockout Mice
Polysaccharides
Glycoproteins
Vaccination
Immunoglobulin G
Lymph Nodes
Ligands
Viruses

ASJC Scopus subject areas

  • Immunology

Cite this

Increased immunogenicity of human immunodeficiency virus gp120 engineered to express Galα1-3Galβ1-4GlcNAc-R epitopes. / Abdel-Motal, Ussama M.; Wang, Shixia; Lu, Shan; Wigglesworth, Kim; Galili, Uri.

In: Journal of Virology, Vol. 80, No. 14, 07.2006, p. 6943-6951.

Research output: Contribution to journalArticle

Abdel-Motal, Ussama M. ; Wang, Shixia ; Lu, Shan ; Wigglesworth, Kim ; Galili, Uri. / Increased immunogenicity of human immunodeficiency virus gp120 engineered to express Galα1-3Galβ1-4GlcNAc-R epitopes. In: Journal of Virology. 2006 ; Vol. 80, No. 14. pp. 6943-6951.
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