A Human Monoclonal Antibody Targeting α-Gal Ameliorates Experimental Cutaneous Leishmaniasis.

Leishmaniasis is a vector-borne disease transmitted by female sand flies infected with Leishmania parasites. Cutaneous leishmaniasis is primarily caused by Leishmania major in the Old World and typically manifests as skin ulcers. The carbohydrate-rich molecules on the surface of Leishmania are crucial for the parasite's infectivity in the vertebrate host and vector. Among these, galactose moieties have been identified as promising targets for vaccines against leishmaniasis. This study investigates the potential of human monoclonal antibodies (mAbs) targeting α-Gal to prevent L major infection. Our results demonstrate that α-Gal-specific mAbs effectively bind to and agglutinate metacyclic and procyclic L major promastigotes. To assess the protective efficacy of these mAbs, we challenged α1,3-galactosyltransferase-deficient mice with L major. The mAb AG030 significantly delayed the onset of skin lesions and reduced the parasite burden. These findings provide proof of principle that α-Gal-targeting mAbs could serve as an intervention to prevent cutaneous leishmaniasis.