Immunity to α-Gal: Toward a Single-Antigen Pan-Vaccine To Control Major Infectious Diseases

Infectious diseases constitute a growing burden for human health worldwide. In particular, vector-borne diseases account for 17% of all infectious diseases and kill about 1 million people annually. These diseases are caused by a diverse group of pathogens including viruses, bacteria, and protozoa that are transmitted by arthropod vectors such as ticks, mosquitoes, sandflies, kissing bugs, and tsetse flies. Among the nonviral vector-borne diseases, malaria, leishmaniasis, Chagas disease, sleeping sickness, and Lyme disease represent the highest burden to human health. Further, vaccines are not available for the prevention and control of these diseases. Among non-vector-borne diseases, tuberculosis caused by mycobacteria of the Mycobacterium tuberculosis complex is one of the world’s most common causes of death from infectious diseases. All pathogens producing these deadly diseases have something in common: the galactose-alpha-1,3-galactose (α-Gal) epitope exposed on their surface (Table 1). During evolution, humans lost the ability to synthesize the carbohydrate α-Gal, which resulted in an almost unique capacity to produce high antibody titers against α-Gal. The immunity to α-Gal may neutralize the pathogens with α-Gal on their surface, and therefore the induction of this protective immune response may constitute an effective intervention for the prevention and control of infectious diseases. The study of the anti-α-Gal immunity will provide the basis to develop a single-antigen “pan-vaccine” to control major infectious diseases. The paper recently published by Moura et al. shows that vaccination with α-Gal protects against cutaneous and visceral leishmaniasis in the α-galactosyltransferase knockout mouse model designed to reproduce the anti-α-Gal response observed in humans. This work extends previous results showing that anti-α-Gal antibodies induced by α-Gal protect against Trypanosoma cruzi and Plasmodium spp. In particular, Yilmaz et al. showed that the anti-α-Gal immunity blocks the transmission of Plasmodium spp. by Anopheles