The αGal HyperAcute® Technology: Enhancing Immunogenicity of Antiviral Vaccines by Exploiting the Natural αGal-Mediated Zoonotic Blockade

P>The alpha Gal HyperAcute((R)) Technology exploits a robust zoonotic blockade to enhance potency of antiviral vaccines. Naturally acquired immunity against the common alpha Gal epitope [galactose-alpha(1,3)-galactose-beta(1,4)N-acetylglucosamine-R (Gal-alpha(1,3)-Gal-beta(1,4)-GlcNAc-R)] is facilitated by the loss of a key enzyme in the epitope's biosynthetic pathway. As human cells are devoid of this epitope, chronic stimulus from gut flora leads to high levels of circulating anti-alpha Gal antibodies and the development of a robust immune pathway. As the alpha Gal epitope is immediately recognized as foreign, the naturally acquired alpha Gal immune pathway in humans serves as a strong barrier to zoonotic infection. The alpha Gal HyperAcute((R)) Technology takes advantage of this natural process to facilitate the rapid presentation of modified antigens to antigen-presenting cells, leading to a strong immune response. The evolutionary immunity to alpha Gal ensures that the presence of alpha Gal epitopes on antigens will lead to a robust immune response involving cross-activation of T(H)1 immunity, characterized by cytokine secretion and increased phagocytic activity, and T(H)2 immunity characterized by high antibody titres. alpha Gal epitopes can be applied to antiviral vaccines by biological, enzymatic or chemical means. Several detection methods that directly and indirectly verify alpha Gal addition are discussed. Enhanced immunogenicity (humoral and cellular) of alpha Gal-modified vaccines is shown for several antiviral vaccine candidates. alpha Gal modification of antiviral vaccine components leads to enhanced immunogenicity. The existing body of literature describing the utility of alpha Gal epitopes as a safe and robust immunostimulatory and -modulatory agent in humans supports the basis for applying the alpha Gal HyperAcute((R)) Technology to the improvement of antiviral vaccines, both new and currently approved.