In silico epitope mapping and experimental evaluation of the Merozoite Adhesive Erythrocytic Binding Protein (MAEBL) as a malaria vaccine candidate

Autor(es):Mostrar menos -

Cravo, Pedro ^{[1, 2, 3]} ; Machado, Renato B. ^[1] ; Leite, Juliana A. ^[4] ; Leda, Taizy ^[1] ; Suwanarusk, Rossarin ^[5] ; Bittencourt, Najara ^[4] ; Albrecht, Letusa ^{[4, 6]} ; Judice, Carla ^[4] ; Lopes, Stefanie C. P. ^{[4, 7]} ; Lacerda, Marcus V. G. ^{[7, 8]} ; Ferreira, Marcelo U. ^[9] ; Soares, Irene S. ^[10] ; Goh, Yun Shan ; Bargieri, Daniel Y. ^[9] ; Nosten, Francois ^{[11, 12]} ; Russell, Bruce ^[13] ; Renia, Laurent ^[5] ; Costa, Fabio T. M. ^[4]

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^[1] Univ Fed Goias, Inst Patol Trop & Saude Publ, GenoBio, Goiania, Go - Brazil

^[2] Univ Nova Lisboa, Global Hlth & Trop Med Ctr GHTM, IHMT, Rua Junqueira 100, P-1349008 Lisbon - Portugal

^[3] Ctr Univ Anapolis, PPG SOMA, Anapolis, Go - Brazil

^[4] Univ Campinas UNICAMP, Dept Genet Evolut Microbiol & Immunol, Lab Trop Dis Prof Dr Luiz Jacintho da Silva, Campinas, SP - Brazil

^[5] ASTAR, Singapore Immunol Network, Singapore - Singapore

^[6] Fundacao Oswaldo Cruz FIOCRUZ, Inst Carlos Chagas, Curitiba, PR - Brazil

^[7] Fundacao Oswaldo Cruz FIOCRUZ, Inst Leonidas & Maria Deane, Manaus, AM - Brazil

^[8] Fundacao Med Trop Dr Heitor Vieira Dourado, Gerencia Malaria, Manaus, AM - Brazil

^[9] Univ Sao Paulo, Dept Parasitol, Sao Paulo, SP - Brazil

^[10] Univ Sao Paulo, Dept Clin & Toxicol Anal, Pharmaceut Sci, Sao Paulo, SP - Brazil

^[11] Mahidol Univ, Fac Trop Med, Shoklo Malaria Res Unit, Mahidol Oxford Trop Med Res Unit, Mae Sot - Thailand

^[12] NUS, Dept Microbiol, Singapore - Singapore

^[13] Univ Oxford, Ctr Trop Med, Nuffield Dept Med, Oxford - England

• Tipo de documento: Artigo Científico
• Fonte: Malaria Journal; v. 17, JAN 10 2018.
• Citações Web of Science: 3

Resumo

Background: Technical limitations for culturing the human malaria parasite Plasmodium vivax have impaired the discovery of vaccine candidates, challenging the malaria eradication agenda. The immunogenicity of the M2 domain of the Merozoite Adhesive Erythrocytic Binding Protein (MAEBL) antigen cloned from the Plasmodium yoelii murine parasite, has been previously demonstrated. Results: Detailed epitope mapping of MAEBL through immunoinformatics identified several MHCI, MHCII and B cell epitopes throughout the peptide, with several of these lying in the M2 domain and being conserved between P. vivax, P. yoelii and Plasmodium falciparum, hinting that the M2-MAEBL is pan-reactive. This hypothesis was tested through functional assays, showing that P. yoelii M2-MAEBL antisera are able to recognize and inhibit erythrocyte invasion from both P. falciparum and P. vivax parasites isolated from Thai patients, in ex vivo assays. Moreover, the sequence of the M2-MAEBL is shown to be highly conserved between P. vivax isolates from the Amazon and Thailand, indicating that the MAEBL antigen may constitute a vaccine candidate outwitting strain-specific immunity. Conclusions: The MAEBL antigen is promising candidate towards the development of a malaria vaccine. (AU)

• Processo FAPESP: 12/16525-2 - Plasmodium vivax: patogênese e infectividade
• Beneficiário: Fabio Trindade Maranhão Costa
• Modalidade de apoio: Auxílio à Pesquisa - Temático