Enhancement of antigen presentation of influenza virus hemagglutinin by the natural human anti-Gal antibody

Immunogenicity of inactivated virus or subviral vaccines may be enhanced by complexing with an IgG antibody. Such antibody would increase the uptake, processing and presentation of the vaccine's antigens by antigen presenting cells (APC), via the adhesion of the antibody-vaccine complex to Fc-receptors on macrophages and other APC. A natural antibody in humans, which may be generally exploited for this purpose, is the natural anti-Gal antibody. This antibody is ubiquitously produced as 1% of circulating IgG in humans and Old World primates, and it interacts specifically with the carbohydrate epitope Galα1–3Galβ1–4GlcNAc-R (termed the α-galactosyl epitope). This epitope is synthesized in large amounts in cells of nonprimate mammals and New World monkeys by the glycosylation enzyme α1,3galactosyltransferase. Here we describe in vitro studies on the ability of anti-Gal to bind to α-galactosyl epitopes on influenza virus propagated in mammalian cells, and to enhance presentation by APC of viral hemagglutinin antigenic determinants to specific helper T cell clones. The various approaches for achieving α-galactosyl epitope expression on virion and subviral vaccines are discussed.