2024-03-28T13:24:05Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1242682019-10-10T13:32:29Zcom_10261_79com_10261_1col_10261_332
Coadministration of the Three Antigenic Leishmania infantum Poly (A) Binding Proteins as a DNA Vaccine Induces Protection against Leishmania major Infection in BALB/c Mice
Soto, Manuel
Corvo, Laura
Garde, Esther
Ramírez, Laura
Bonay, Pedro
Alonso, Carlos
Iborra, Salvador
Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasil)
Instituto de Salud Carlos III
Ministerio de Ciencia e Innovación (España)
Highly conserved intracellular proteins from Leishmania have been described as antigens in natural and experimental infected mammals. The present study aimed to evaluate the antigenicity and prophylactic properties of the Leishmania infantum Poly (A) binding proteins (LiPABPs). Three different members of the LiPABP family have been described. Recombinant tools based on these proteins were constructed: recombinant proteins and DNA vaccines. The three recombinant proteins were employed for coating ELISA plates. Sera from human and canine patients of visceral leishmaniasis and human patients of mucosal leishmaniasis recognized the three LiPABPs. In addition, the protective efficacy of a DNA vaccine based on the combination of the three Leishmania PABPs has been tested in a model of progressive murine leishmaniasis: BALB/c mice infected with Leishmania major. The induction of a Th1-like response against the LiPABP family by genetic vaccination was able to down-regulate the IL-10 predominant responses elicited by parasite LiPABPs after infection in this murine model. This modulation resulted in a partial protection against L. major infection. LiPABP vaccinated mice showed a reduction on the pathology that was accompanied by a decrease in parasite burdens, in antibody titers against Leishmania antigens and in the IL-4 and IL-10 parasite-specific mediated responses in comparison to control mice groups immunized with saline or with the non-recombinant plasmid. The results presented here demonstrate for the first time the prophylactic properties of a new family of Leishmania antigenic intracellular proteins, the LiPABPs. The redirection of the immune response elicited against the LiPABP family (from IL-10 towards IFN-γ mediated responses) by genetic vaccination was able to induce a partial protection against the development of the disease in a highly susceptible murine model of leishmaniasis.
The study was supported in Spain by grants from Ministerio de Ciencia e Innovación FIS PI11/00095 and FISPI14/00366 from the Instituto de Salud Carlos III within the Network of Tropical Diseases Research (VI P I+D+I 2008-2011, ISCIII -Subdirección General de Redes y Centros de Investigación Cooperativa (RD12/0018/0009)). This work was also supported in Brazil by a grant from CNPq (Ciencia sem Fronteiras-PVE 300174/2014-4)
Peer Reviewed
2015-05-08
2015-11-02T11:10:22Z
artículo
http://purl.org/coar/resource_type/c_6501
doi: 10.1371/journal.pntd.0003751
issn: 1935-2735
PLoS Neglected Tropical Diseases 9(5): e0003751 (2015)
http://hdl.handle.net/10261/124268
10.1371/journal.pntd.0003751
http://dx.doi.org/10.13039/501100003593
http://dx.doi.org/10.13039/501100004587
http://dx.doi.org/10.13039/501100004837
25955652
Publisher's version
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open
Public Library of Science