TY - JOUR
T1 - A recombinant Leishmania amastigote-specific protein, rLiHyG, with adjuvants, protects against infection with Leishmania infantum
AU - Machado, Amanda S.
AU - Lage, Daniela P.
AU - Vale, Danniele L.
AU - Freitas, Camila S.
AU - Linhares, Flávia P.
AU - Cardoso, Jamille M.O.
AU - Pereira, Isabela A.G.
AU - Ramos, Fernanda F.
AU - Tavares, Grasiele S.V.
AU - Ludolf, Fernanda
AU - Oliveira-da-Silva, João A.
AU - Bandeira, Raquel S.
AU - Simões, Aratti C.
AU - Duarte, Mariana C.
AU - Oliveira, Jamil 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:
© 2022 Elsevier B.V.
PY - 2022/6
Y1 - 2022/6
N2 - Vaccination against visceral leishmaniasis (VL) should be considered as a control measure to protect against disease, and amastigote-specific proteins could help to develop such vaccines, since this parasite form is in contact with the host immune system during the active disease. In this study, a Leishmania amastigote-specific protein, LiHyG, was evaluated as recombinant protein (rLiHyG) as vaccine candidate against Leishmania infantum infection in BALB/c mice. The protein was associated with saponin (rLiHyG/Sap) or Poloxamer 407-based polymeric micelles (rLiHyG/Mic) as adjuvants, and animals receiving saline, saponin or micelle as controls. Immunological and parasitological analyses were performed before (n = 8 per group; as primary endpoint) and after (n = 8 per group; as secondary endpoint) infection. Results showed that, in both endpoints, rLiHyG/Sap and rLiHyG/Mic induced higher levels of IFN-γ, IL-12 and GM-CSF in spleen cell cultures from vaccinated animals, besides elevated presence of IgG2a isotype antibodies. Decreased hepatotoxicity and ‘positive lymphoproliferative response were also found after challenge. Such findings reflected in significantly lower levels of parasite load found in their spleens, livers, bone marrows and draining lymph nodes. In conclusion, rLiHyG associated with Th1-type adjuvant could be considered for future studies as vaccine candidate to protect against VL.
AB - Vaccination against visceral leishmaniasis (VL) should be considered as a control measure to protect against disease, and amastigote-specific proteins could help to develop such vaccines, since this parasite form is in contact with the host immune system during the active disease. In this study, a Leishmania amastigote-specific protein, LiHyG, was evaluated as recombinant protein (rLiHyG) as vaccine candidate against Leishmania infantum infection in BALB/c mice. The protein was associated with saponin (rLiHyG/Sap) or Poloxamer 407-based polymeric micelles (rLiHyG/Mic) as adjuvants, and animals receiving saline, saponin or micelle as controls. Immunological and parasitological analyses were performed before (n = 8 per group; as primary endpoint) and after (n = 8 per group; as secondary endpoint) infection. Results showed that, in both endpoints, rLiHyG/Sap and rLiHyG/Mic induced higher levels of IFN-γ, IL-12 and GM-CSF in spleen cell cultures from vaccinated animals, besides elevated presence of IgG2a isotype antibodies. Decreased hepatotoxicity and ‘positive lymphoproliferative response were also found after challenge. Such findings reflected in significantly lower levels of parasite load found in their spleens, livers, bone marrows and draining lymph nodes. In conclusion, rLiHyG associated with Th1-type adjuvant could be considered for future studies as vaccine candidate to protect against VL.
KW - Amastigote
KW - Hypothetical protein
KW - Polymeric micelles
KW - Saponin
KW - Vaccine
KW - Visceral leishmaniasis
UR - http://www.scopus.com/inward/record.url?scp=85126854017&partnerID=8YFLogxK
U2 - 10.1016/j.actatropica.2022.106412
DO - 10.1016/j.actatropica.2022.106412
M3 - Article
C2 - 35305943
AN - SCOPUS:85126854017
SN - 0001-706X
VL - 230
JO - Acta Tropica
JF - Acta Tropica
M1 - 106412
ER -