Untargeted Metabolomic Studies to Assess Immunogenicity of Centrin Gene-Deleted Leishmania major Parasites in a Mouse Model

Abstract

Leishmaniasis is a neglected tropical disease that causes severe morbidity and is endemic in 98 countries. Attempts to develop a vaccine have been unfruitful, aside from leishmanization (deliberate inoculation with a miniscule number of virulent Leishmania major parasites that cause cutaneous lesions). However, leishmanization is no longer practiced due to safety concerns. A L. major parasite strain attenuated through gene deletion has shown promising results in preclinical studies in providing protection against wildtype infection without itself causing pathogenesis; Vaccination with such live, attenuated Leishmania parasites is therefore termed second-generation leishmanization. Towards assessing the safety and immunogenicity characteristics of this vaccine strain, untargeted metabolomics analysis was conducted on ears and draining lymph nodes of mice infected with the vaccine strain or the wildtype strain. The studies described here will enable understanding of immune mechanisms of protection, discovery of biomarkers or immunogenicity, and to advance the vaccine towards clinical trials.