2024-03-29T10:42:44Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/144582023-10-06T12:18:31Zcom_20.500.12105_2060com_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_2061
00925njm 22002777a 4500
dc
Larraga, Jaime
author
Alcolea, Pedro J
author
Alonso, Ana M
author
Martins, Luis T C
author
Moreno-Iruela, Inmaculada
author
Dominguez-Rodriguez, Mercedes
author
Larraga, Vicente
author
2022-02-03
Leishmania 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 Leishmania 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 Leishmania infantum 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 L. infantum 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 L. infantum in the Syrian hamster model.
Vaccines (Basel). 2022 Feb 3;10(2):231.
2076-393X
http://hdl.handle.net/20.500.12105/14458
35214689
10.3390/vaccines10020231
Vaccines
Leishmania
Infection
Ubiquitin-conjugating enzyme E2
Vaccines
Leishmania infantum UBC1 in Metacyclic Promastigotes from Phlebotomus perniciosus, a Vaccine Candidate for Zoonotic Visceral Leishmaniasis