TY - JOUR
T1 - Recombinant endonuclease III protein from Leishmania infantum associated with Th1-type adjuvants is immunogenic and induces protection against visceral leishmaniasis
AU - Lage, Daniela P.
AU - Machado, Amanda S.
AU - Freitas, Camila S.
AU - Vale, Danniele L.
AU - Linhares, Flávia P.
AU - Cardoso, Jamille M.O.
AU - Oliveira-da-Silva, João A.
AU - Ramos, Fernanda F.
AU - Pereira, Isabela A.G.
AU - Ludolf, Fernanda
AU - Tavares, Grasiele S.V.
AU - Bandeira, Raquel S.
AU - Oliveira, Jamil S.
AU - Menezes-Souza, Daniel
AU - Duarte, Mariana C.
AU - Galdino, Alexsandro S.
AU - Christodoulides, Myron
AU - Chávez-Fumagalli, Miguel A.
AU - Roatt, Bruno M.
AU - Martins, Vívian T.
AU - Coelho, Eduardo A.F.
N1 - Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/3
Y1 - 2023/3
N2 - Vaccination against visceral leishmaniasis (VL) should be considered as a safe and effective measure to disease control; however, few vaccines are available against canine VL and there is no an approved human vaccine. In this context, in the present study, we evaluated the endonuclease III (ENDO) protein, which was recently showed to be antigenic for human disease, as a vaccine candidate against Leishmania infantum infection. The recombinant protein (rENDO) was administered in BALB/c mice alone or associated with saponin (rENDO/Sap) or micelles (rENDO/Mic) as adjuvants. Controls received saline, saponin or empty micelles. Results showed that both rENDO/Sap and rENDO/Mic compositions induced higher levels of IFN-γ, IL-12, TNF-α, and GM-CSF cytokines, besides nitrite and IgG2a isotype antibodies, before and after challenge infection, which were related to both CD4+ and CD8+ T cell subtypes. The immunological results contributed to significant reductions in the parasite load found in the spleens, livers, bone marrows and draining lymph nodes of the vaccinated animals. In general, mice immunized with rENDO/Mic presented a slightly higher Th1-type cellular and humoral immune response, as compared to those receiving rENDO/Sap. In addition, saponin caused a slight to moderate inflammatory edema in their vaccinated footpads, which was not observed when micelles were used with rENDO. In addition, a preliminary analysis showed that the recombinant protein was immunogenic to human cells cultures, since PBMCs from treated VL patients and healthy subjects showed higher lymphoproliferation and IFN-γ production in the culture supernatants. In conclusion, data suggest that rENDO could be considered as a candidate to be evaluated in future studies as vaccine to protect against VL.
AB - Vaccination against visceral leishmaniasis (VL) should be considered as a safe and effective measure to disease control; however, few vaccines are available against canine VL and there is no an approved human vaccine. In this context, in the present study, we evaluated the endonuclease III (ENDO) protein, which was recently showed to be antigenic for human disease, as a vaccine candidate against Leishmania infantum infection. The recombinant protein (rENDO) was administered in BALB/c mice alone or associated with saponin (rENDO/Sap) or micelles (rENDO/Mic) as adjuvants. Controls received saline, saponin or empty micelles. Results showed that both rENDO/Sap and rENDO/Mic compositions induced higher levels of IFN-γ, IL-12, TNF-α, and GM-CSF cytokines, besides nitrite and IgG2a isotype antibodies, before and after challenge infection, which were related to both CD4+ and CD8+ T cell subtypes. The immunological results contributed to significant reductions in the parasite load found in the spleens, livers, bone marrows and draining lymph nodes of the vaccinated animals. In general, mice immunized with rENDO/Mic presented a slightly higher Th1-type cellular and humoral immune response, as compared to those receiving rENDO/Sap. In addition, saponin caused a slight to moderate inflammatory edema in their vaccinated footpads, which was not observed when micelles were used with rENDO. In addition, a preliminary analysis showed that the recombinant protein was immunogenic to human cells cultures, since PBMCs from treated VL patients and healthy subjects showed higher lymphoproliferation and IFN-γ production in the culture supernatants. In conclusion, data suggest that rENDO could be considered as a candidate to be evaluated in future studies as vaccine to protect against VL.
KW - Adjuvants
KW - Endonuclease III
KW - Immune response
KW - Recombinant protein
KW - Vaccine
KW - Visceral leishmaniasis
UR - http://www.scopus.com/inward/record.url?scp=85147123797&partnerID=8YFLogxK
U2 - 10.1016/j.molimm.2023.01.011
DO - 10.1016/j.molimm.2023.01.011
M3 - Article
C2 - 36731193
AN - SCOPUS:85147123797
SN - 0161-5890
VL - 155
SP - 79
EP - 90
JO - Molecular Immunology
JF - Molecular Immunology
ER -