Journal
JOURNAL OF VIROLOGY
Volume 80, Issue 14, Pages 6943-6951Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.00310-06
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Funding
- NIAID NIH HHS [R21 AI058749, AI58749] Funding Source: Medline
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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 Gal alpha 1-3Gal beta 1-4GlcNAc-R (alpha-gal) epitopes. These epitopes are ligands for the natural anti-Gal antibody constituting similar to 1% of immunoglobulin G in humans. We hypothesize that vaccination with gp120 expressing et-gal epitopes (gp120(alpha gal)) 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 Fc gamma 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 alpha-1,3-galactosyltransferase knockout mice, which produce anti-Gal. Mice immunized with gp120(alpha gal) 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 gp120(alpha gal) than in mice immunized with gp120. It is suggested that gp120(alpha gal) can serve as a platform for anti-Gal-mediated targeting of additional vaccinating HIV proteins fused to gp120(alpha gal), thereby creating effective prophylactic vaccines.
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