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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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]
Total Authors: 11
[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
Total Affiliations: 5
Document type: Journal article
Source: MICROORGANISMS; v. 8, n. 6 JUN 2020.
Web of Science Citations: 0

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)

FAPESP's process: 12/13032-5 - Generation and analysis of the immunogenicity of recombinant proteins based on the different allelic forms of the circumsporozoite antigen of Plasmodium vivax aiming at the development of a universal vaccine against malaria
Grantee:Irene da Silva Soares
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 14/18102-7 - Preclinical tests of recombinant adenovirus-based protein and vaccine formulations expressing the Plasmodium vivax circumsporozoite protein
Grantee:Alba Marina Gimenez
Support Opportunities: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 18/17364-9 - Evaluation of the immunogenicity of novel multi-stage recombinant proteins candidates for the development of a vaccine to Plasmodium vivax
Grantee:Tarsila Mendes de Camargo Oliva
Support Opportunities: Scholarships in Brazil - Post-Doctorate