Leishmania infantum UBC1 in Metacyclic Promastigotes from Phlebotomus perniciosus , a Vaccine Candidate for Zoonotic Visceral Leishmaniasis

• Published in: Vaccines (Basel) 2022-02, Vol.10 (2), p.231
• Main Authors: Larraga, Jaime, Alcolea, Pedro J, Alonso, Ana M, Martins, Luis T C, Moreno, Inmaculada, Domínguez, Mercedes, Larraga, Vicente
• Format: Article
• Language: English
• Subjects: Cell division; Developing countries; Enzymes; Gene expression; Hamsters; Histocompatibility antigen HLA; Homology; Immunization; infection; Infections; Infectivity; LDCs; Leishmania; Leishmania infantum; Low level; Mammals; Microscopy; Morbidity; Parasites; Parasitic diseases; Promastigotes; Proteins; Spleen; Splenocytes; Transcription; Ubiquitin; Ubiquitin-conjugating enzyme; ubiquitin-conjugating enzyme E2; Vaccines; Vector-borne diseases; Visceral leishmaniasis; Zoonoses; γ-Interferon
• ISSN: 2076-393X; 2076-393X
• DOI: 10.3390/vaccines10020231

parasites cause outstanding levels of morbidity and mortality in many developing countries in tropical and subtropical regions. Numerous gene expression profiling studies have been performed comparing different species' life-cycles and stage forms in regard to their distinct infective ability. Based on expression patterns, homology to human orthologues, in silico HLA-binding predictions, and annotated functions, we were able to select several vaccine candidates which are currently under study. One of these candidates is the ubiquitin-conjugating enzyme E2 (LiUBC1), whose relative levels, subcellular location, in vitro infectivity in the U937 myeloid human cell model, and protection levels in Syrian hamsters against infection were studied herein. LiUBC1 displays a low level of similarity with the mammalian orthologs and relevant structure differences, such as the C-terminal domain, which is absent in the human ortholog. LiUBC1 is present in highly infective promastigotes. Knock-in parasites overexpressing the enzyme increased their infectivity, according to in vitro experiments. Syrian hamsters immunized with the recombinant LiUBC1 protein did not show any parasite burden in the spleen, unlike the infection control group. The IFN-γ transcript levels in splenocytes were significantly higher in the LiUBC1 immunized group. Therefore, LiUBC1 induced partial protection against in the Syrian hamster model.