A Multistage Formulation Based on Full-Length CSP and AMA-1 Ectodomain ofPlasmodium vivaxInduces High Antibody Titers and T-cells and Partially Protects Mice Challenged with a TransgenicPlasmodium bergheiParasite

Autor(es):Mostrar menos -

Lima, Luciana C. ^[1] ; Marques, Rodolfo F. ^[1] ; Gimenez, Alba Marina ^[1] ; Francoso, Katia S. ^[1] ; Aliprandini, Eduardo ^[2] ; Camargo, Tarsila M. ^[1] ; Aguiar, Anna Caroline C. ^[3] ; Pereira, Dhelio B. ^[4] ; Renia, Laurent ^[5] ; Amino, Rogerio ^[2] ; Soares, Irene S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, BR-05508000 Sao Paulo, SP - Brazil

^[2] Inst Pasteur, Unit Malaria Infect & Immun, F-75015 Paris - France

^[3] Univ Sao Paulo, Sao Carlos Inst Phys, BR-13563120 Sao Carlos, SP - Brazil

^[4] Ctr Pesquisas Med Trop, BR-76812329 Porto Velho, RO - Brazil

^[5] Agcy Sci Technol & Res, Biopolis, Singapore Immunol Network, Singapore 138632 - Singapore

• Tipo de documento: Artigo Científico
• Fonte: MICROORGANISMS; v. 8, n. 6 JUN 2020.
• Citações Web of Science: 0

Resumo

Infections withPlasmodium vivaxare predominant in the Americas, representing 75% of malaria cases. Previously perceived as benign, malaria vivax is, in fact, a highly debilitating and economically important disease. Considering the high complexity of the malaria parasite life cycle, it has been hypothesized that an effective vaccine formulation againstPlasmodiumshould contain multiple antigens expressed in different parasite stages. Based on that, we analyzed a recombinantP. vivaxvaccine formulation mixing the apical membrane antigen 1 ectodomain (PvAMA-1) and a full-length circumsporozoite protein (PvCSP-All(FL)) previously studied by our group, which elicits a potent antibody response in mice. Genetically distinct strains of mice (C57BL/6 and BALB/c) were immunized with the proteins, alone or in combination, in the presence of poly(I:C) adjuvant, a TLR3 agonist. In C57BL/6, high-antibody titers were induced against PvAMA-1 and the three PvCSP variants (VK210, VK247, andP. vivax-like). Meanwhile, mixing PvAMA-1 with PvCSP-All(FL)had no impact on total IgG antibody titers, which were long-lasting. Moreover, antibodies from immunized mice recognized VK210 sporozoites and blood-stage parasites by immunofluorescence assay. However, in the BALB/c model, the antibody response against PvCSP-All(FL)was relatively low. PvAMA-1-specific CD3(+)CD4(+)and CD3(+)CD8(+)T-cell responses were observed in C57BL/6 mice, and the cellular response was impaired by PvCSP-All(FL)combination. More relevant, the multistage vaccine formulation provided partial protection in mice challenged with a transgenicPlasmodium bergheisporozoite expressing the homologous PvCSP protein. (AU)

• Processo FAPESP: 12/13032-5 - Geração e análise da imunogenicidade de proteínas recombinantes baseadas nas diferentes formas alélicas do antígeno circumsporozoíta de Plasmodium vivax visando o desenvolvimento de uma vacina universal contra malária
• Beneficiário: Irene da Silva Soares
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/18102-7 - Testes pré-clínicos de formulações vacinais baseadas em proteínas e adenovírus recombinantes expressando a proteína do circumsporozoíta de Plasmodium vivax
• Beneficiário: Alba Marina Gimenez
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 18/17364-9 - Avaliação da imunogenicidade de novas proteínas recombinantes multi- estágio candidatas ao desenvolvimento de uma vacina contra o Plasmodium vivax
• Beneficiário: Tarsila Mendes de Camargo Oliva
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado