Mechanism for increased immunogenicity of vaccines that form in vivo immune complexes with the natural anti-Gal antibody

Anti-Gal constitutes similar to 1% of circulating IgG in humans and interacts specifically with alpha-gal epitopes. We reported previously that expression of a-gal epitopes on HIV gp120 and influenza virus vaccines increases immunogenicity by similar to 100-fold. We hypothesize that immunogenicity of any microbial vaccine can be markedly increased by linked a-gal epitopes due to in vivo formation of immune complexes with anti-Gal and the effective internalization of such immune complexes by APC, via Fc/Fc gamma R interaction. The increased transport to lymph nodes and processing of anti-Gal complexed vaccines internalized by APC, results in effective activation of vaccine specific CD4(+) and CD8(+) T cells, and high cellular and humoral immune response. This universal mechanism for anti-Gal mediated increased immunogenicity is demonstrated in alpha 1,3galactosyltransferase knockout mice with ovalbumin as a model vaccine. (C) 2009 Elsevier Ltd. All rights reserved.