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Recombinant proteins of Plasmodium malariae merozoite surface protein 1 (PmMSP1): Testing immunogenicity in the BALB/c model and potential use as diagnostic tool

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Elizardez, Yelina B. [1] ; Fotoran, Wesley L. [2] ; Galisteo Junior, Andre S. J. [3] ; Curado, Izilda [4] ; Kesper Junior, Norival [3] ; Monteiro, Eliana F. [1] ; Neto, Irineu Romero [3] ; Wunderlich, Gerhard [2] ; Kirchgatter, Karin [1]
Número total de Autores: 9
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Med Trop, Superintendencia Controle Endemias, Nucleo Estudos Malaria, Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, Sao Paulo - Brazil
[3] Univ Sao Paulo, Inst Med Trop, Lab Protozool, Sao Paulo - Brazil
[4] Superintendencia Controle Endemias Estado Sao Paul, Lab Imunoepidemiol, Sao Paulo - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: PLoS One; v. 14, n. 7 JUL 25 2019.
Citações Web of Science: 0

Background Plasmodium malariae is the third most prevalent human malaria-causing species and has a patchy, but ample distribution in the world. Humans can host the parasite for years without presenting significant symptoms, turning its diagnosis and control into a difficult task. Here, we investigated the immunogenicity of recombinant proteins of P. malariae MSP1. Methods Five regions of PmMSP1 were expressed in Escherichia coli as GST-fusion proteins and immunized in BALB/c mice. The specificity, subtyping, and affinity of raised antibodies were evaluated by enzyme-linked immunosorbent assays. Cellular immune responses were analyzed by lymphoproliferation assays and cytokine levels produced by splenocytes were detected by cytometry. Results We found that N-terminal, central regions, and PmMSP1(19) are strongly immunogenic in mice. After three doses, the induced immune responses remained high for 70 days. While antibodies induced after immunization with N-terminal and central regions showed similar affinities to the target antigens, affinities of IgG against PmMSP1(19) were higher. All proteins induced similar antibody subclass patterns (predominantly IgG1, IgG2a, and IgG2b), characterizing a mixed Th1/Th2 response. Further, autologous stimulation of splenocytes from immunized mice led to the secretion of IL2 and IL4, independently of the antigen used. Importantly, IgG from P. malariae-exposed individuals reacted against PmMSP1 recombinant proteins with a high specificity. On the other hand, sera from P. vivax or P. falciparum-infected individuals did not react at all against recombinant PmMSP1 proteins. Conclusion Recombinant PmMSP1 proteins are very useful diagnostic markers of P. malariae in epidemiological studies or in the differential diagnosis of malaria caused by this species. Immunization with recombinant PmMSP1 proteins resulted in a significant humoral immune response, which may turn them potential component candidates for a vaccine against P. malariae. (AU)

Processo FAPESP: 16/04559-0 - Análise do relacionamento filogeográfico e imunológico de Plasmodium malariae e Plasmodium brasilianum
Beneficiário:Karin Kirchgatter Hildebrand
Linha de fomento: Auxílio à Pesquisa - Regular