PMID- 35339043 OWN - NLM STAT- MEDLINE DCOM- 20220414 LR - 20220531 IS - 1096-0023 (Electronic) IS - 1043-4666 (Linking) VI - 153 DP - 2022 May TI - Recombinant guanosine-5'-triphosphate (GTP)-binding protein associated with Poloxamer 407-based polymeric micelles protects against Leishmania infantum infection. PG - 155865 LID - S1043-4666(22)00074-6 [pii] LID - 10.1016/j.cyto.2022.155865 [doi] AB - Leishmania virulence proteins should be considered as vaccine candidates against disease, since they are involved in developing infection in mammalian hosts. In a previous study, a Leishmania guanosine-5'-triphosphate (GTP)-binding protein was identified as a potential parasite virulence factor. In the present work, the gene encoding GTP was cloned and the recombinant protein (rGTP) was evaluated as a vaccine candidate against Leishmania infantum infection. The protein was associated with saponin (rGTP/Sap) or Poloxamer 407-based micelles (rGTP/Mic) as adjuvants, and protective efficacy was investigated in BALB/c mice after parasite challenge. Both rGTP/Sap and rGTP/Mic compositions induced a Th1-type immune response in vaccinated animals, with significantly higher levels of IFN-gamma, IL-12, IL-2, TNF-alpha, GM-CSF, nitrite, specific IgG2a isotype antibody and positive lymphoproliferation, when compared to the control groups. This response was accompanied by significantly lower parasite load in the spleens, livers, bone marrows and draining lymph nodes of the animals. Immunological and parasitological evaluations indicated that rGTP/Mic induced a more polarized Th1-type response and higher reduction in the organ parasitism, and with lower hepatotoxicity, when compared to the use of rGTP/Sap. In conclusion, our preliminary data suggest that rGTP could be considered for further development as a vaccine candidate to protect against VL. CI - Copyright (c) 2022 Elsevier Ltd. All rights reserved. FAU - Lage, Daniela P AU - Lage DP AD - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, 30130-100, Belo Horizonte, Minas Gerais, Brazil. FAU - Machado, Amanda S AU - Machado AS AD - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, 30130-100, Belo Horizonte, Minas Gerais, Brazil. FAU - Vale, Danniele L AU - Vale DL AD - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, 30130-100, Belo Horizonte, Minas Gerais, Brazil. FAU - Freitas, Camila S AU - Freitas CS AD - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, 30130-100, Belo Horizonte, Minas Gerais, Brazil. FAU - Linhares, Flavia P AU - Linhares FP AD - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, 30130-100, Belo Horizonte, Minas Gerais, Brazil. FAU - Cardoso, Jamille M O AU - Cardoso JMO AD - Laboratorio de Imunopatologia, Nucleo de Pesquisas em Ciencias Biologicas/NUPEB, Departamento de Ciencias Biologicas, Insituto de Ciencias Exatas e Biologicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil. FAU - Pereira, Isabela A G AU - Pereira IAG AD - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, 30130-100, Belo Horizonte, Minas Gerais, Brazil. FAU - Ramos, Fernanda F AU - Ramos FF AD - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, 30130-100, Belo Horizonte, Minas Gerais, Brazil. FAU - Tavares, Grasiele S V AU - Tavares GSV AD - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, 30130-100, Belo Horizonte, Minas Gerais, Brazil. FAU - Ludolf, Fernanda AU - Ludolf F AD - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, 30130-100, Belo Horizonte, Minas Gerais, Brazil. FAU - Oliveira-da-Silva, Joao A AU - Oliveira-da-Silva JA AD - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, 30130-100, Belo Horizonte, Minas Gerais, Brazil. FAU - Bandeira, Raquel S AU - Bandeira RS AD - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, 30130-100, Belo Horizonte, Minas Gerais, Brazil. FAU - Silva, Alessandra M AU - Silva AM AD - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, 30130-100, Belo Horizonte, Minas Gerais, Brazil. FAU - Simoes, Luciana C AU - Simoes LC AD - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, 30130-100, Belo Horizonte, Minas Gerais, Brazil. FAU - Reis, Thiago A R AU - Reis TAR AD - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, 30130-100, Belo Horizonte, Minas Gerais, Brazil. FAU - Oliveira, Jamil S AU - Oliveira JS AD - Departamento de Bioquimica e Imunologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte, 31270-901 Minas Gerais, Brazil. FAU - Christodoulides, Myron AU - Christodoulides M AD - Neisseria Research Group, Molecular Microbiology, School of Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton SO16 6YD, England. FAU - Chavez-Fumagalli, Miguel A AU - Chavez-Fumagalli MA AD - Universidad Catolica de Santa Maria, Urb. San Jose S/N, Umacollo, Arequipa, Peru. FAU - Roatt, Bruno M AU - Roatt BM AD - Laboratorio de Imunopatologia, Nucleo de Pesquisas em Ciencias Biologicas/NUPEB, Departamento de Ciencias Biologicas, Insituto de Ciencias Exatas e Biologicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil. FAU - Martins, Vivian T AU - Martins VT AD - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, 30130-100, Belo Horizonte, Minas Gerais, Brazil. FAU - Coelho, Eduardo A F AU - Coelho EAF AD - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, 30130-100, Belo Horizonte, Minas Gerais, Brazil; Departamento de Patologia Clinica, COLTEC, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil. Electronic address: eduardoferrazcoelho@yahoo.com.br. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220323 PL - England TA - Cytokine JT - Cytokine JID - 9005353 RN - 0 (Antigens, Protozoan) RN - 0 (Carrier Proteins) RN - 0 (Micelles) RN - 0 (Polyphosphates) RN - 0 (Recombinant Proteins) RN - 106392-12-5 (Poloxamer) RN - 12133JR80S (Guanosine) RN - 86-01-1 (Guanosine Triphosphate) RN - NU43IAG5BC (triphosphoric acid) SB - IM MH - Animals MH - Antigens, Protozoan MH - Carrier Proteins MH - Guanosine MH - Guanosine Triphosphate MH - *Leishmania infantum MH - *Leishmaniasis MH - *Leishmaniasis, Visceral MH - Mammals MH - Mice MH - Mice, Inbred BALB C MH - Micelles MH - Poloxamer MH - Polyphosphates MH - Recombinant Proteins OTO - NOTNLM OT - GTP-binding protein OT - Immune response OT - Micelle OT - Saponin OT - Vaccine OT - Visceral leishmaniasis EDAT- 2022/03/27 06:00 MHDA- 2022/04/15 06:00 CRDT- 2022/03/26 20:11 PHST- 2021/11/05 00:00 [received] PHST- 2022/02/12 00:00 [revised] PHST- 2022/03/09 00:00 [accepted] PHST- 2022/03/27 06:00 [pubmed] PHST- 2022/04/15 06:00 [medline] PHST- 2022/03/26 20:11 [entrez] AID - S1043-4666(22)00074-6 [pii] AID - 10.1016/j.cyto.2022.155865 [doi] PST - ppublish SO - Cytokine. 2022 May;153:155865. doi: 10.1016/j.cyto.2022.155865. Epub 2022 Mar 23.