Immunogenicity of suboptimal viral vaccines is increased by targeting vaccines to antigen presenting cells (APC) for effective uptake, using the natural anti-Gal antibody which constitutes 1% of immunoglobulins in humans. Anti-Gal interacts with “α-gal epitopes” (Galα1-3Galβ1-4GlcNAc-R) which can be synthesized on viral glycoproteins by recombinant α1,3galactosyltransferase (α1,3GT). Viral vaccines carrying α-gal epitopes form in situ immune complexes with anti-Gal. The immunocomplexed antibody binds via its Fc portion to Fcγ receptors on APC and induces uptake of the vaccine, which is much higher than the physiologic uptake by APC via random endocytosis. Studies on increased immunogenicity of viral vaccines were performed in the experimental model of α1,3GT knockout mice which produce anti-Gal. Recombinant gp120 of HIV and inactivated influenza virus, both engineered to carry α-gal epitopes, were studied as vaccines. The increased uptake of these vaccines resulted in effective processing and presentation of their immunogenic peptides and induction of 10 to 100-fold higher T and B cell responses in comparison to vaccines lacking α-gal epitopes. The studies with vaccinating influenza virus carrying α-gal epitopes further demonstrated ~10-fold increased resistance to challenge with live virus in comparison to mice immunized with virus lacking this epitope. Virus matrix or core proteins lacking carbohydrate chains also can be targeted by anti-Gal to APC by producing them as fusion proteins with envelope glycoproteins engineered to carry α-gal epitopes. Thus, fusion of HIV core protein p24 with gp120, followed by synthesis of α-gal epitopes on carbohydrate chains of the fusion product markedly increased immunogenicity of p24. Synthesis of α-gal epitopes on viral vaccines may also be achieved by an intracellular pathway in cell lines that contain several α1,3GT transgene copies. The high activity of α1,3GT within these cells results in synthesis of multiple α-gal epitopes on propagated viruses or on viral glycoproteins produced in such cell lines.