Mechanism for increased immunogenicity of vaccines that form in vivo immune complexes with the natural anti-Gal antibody.
Anti-Gal constitutes approximately 1% of circulating IgG in humans and interacts specifically with alpha-gal epitopes. We reported previously that expression of alpha-gal epitopes on HIV gp120 and influenza virus vaccines increases immunogenicity by approximately 100-fold. We hypothesize that immunogenicity of any microbial vaccine can be markedly increased by linked alpha-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/FcgammaR 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 alpha1,3galactosyltransferase knockout mice with ovalbumin as a model vaccine.
Abdel-Motal
Ussama M
UM
University of Massachusetts Medical School, Worcester, MA 01655, USA.
Wigglesworth
Kim
K
Galili
Uri
U
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology / Q000378:metabolism*; D000936:Antigen-Antibody Complex / Q000276:immunology / Q000378:metabolism*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism*; D002645:Chickens; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005700:Galactosyltransferases / Q000008:administration & dosage / Q000172:deficiency / Q000276:immunology*; D006801:Humans; D007279:Injections, Subcutaneous; D008081:Liposomes; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011817:Rabbits
D000907:Antibodies, Bacterial; D000936:Antigen-Antibody Complex; D001428:Bacterial Vaccines; D008081:Liposomes; C110366:OVA-8; D010446:Peptide Fragments; D010047:Ovalbumin; D005700:Galactosyltransferases; C487611:alpha 1,3 galactosyltransferase, mouse