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Master's Dissertation
DOI
https://doi.org/10.11606/D.9.2011.tde-20122011-083623
Document
Author
Full name
Amanda Romagnoli Bitencourt
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2011
Supervisor
Committee
Soares, Irene da Silva (President)
Ferreira, Joseli de Oliveira
Stephano, Marco Antonio
Title in Portuguese
Avaliação das propriedades imunogênicas das proteínas 3α e 3β da superfície do merozoíto de Plasmodium vivax
Keywords in Portuguese
Malaria
MSP-3
Plasmodium vivax
Vacina recombinante
Abstract in Portuguese
O avanço no desenvolvimento de uma vacina contra o Plasmodium vivax exige a identificação de antígenos capazes de induzir uma resposta imune protetora contra a malária. O presente estudo avalia o potencial da proteína-3 da superfície de merozoítos de P. vivax (PvMSP-3), como candidata a vacina. As proteínas recombinantes representando a região C-terminal da MSP-3α e diferentes regiões (N e C-terminal e proteína inteira) da MSP-3β de P. vivax foram utilizadas como antígeno. A imunogenicidade destas proteínas recombinantes foi avaliada em camundongos BALB/c, utilizando adjuvantes agonistas de TLR (flagelina FliC de Salmonella Typhimurium e CpG ODN) ou adjuvantes convencionais, tais como hidróxido de alumínio, saponinas, TiterMax Gold e adjuvante incompleto de Freund. Os títulos de anticorpos IgG foram determinados por ELISA utilizando soros de camundongos coletados duas semanas após cada dose de imunização. Nossos resultados demonstraram que a MSP-3α e a MSP-3β foram capazes de induzir altos títulos de anticorpos em camundongos na presença de diferentes adjuvantes, incluindo agonistas de TLR. Dentre as formulações testadas, aquelas contendo os adjuvantes CPG ODN 1826, Quil A, TiterMax e adjuvante incompleto de Freund foram mais imunogênicas e, portanto, mais promissoras para os ensaios pré-clínicos em primatas não-humanos. Usando camundongos TLR-4 KO, nós demonstramos que a proteína MSP-3β tem uma propriedade adjuvante intrínseca que é independente do TLR4 e que a contaminação por LPS na proteína purificada não desempenha qualquer papel no nosso sistema.
Title in English
Analysis of the immunogenic properties of protein 3α and 3β of the merozoite surface of Plasmodium vivax
Keywords in English
Malaria
MSP-3
Plasmodium vivax
Recombinant vaccine
Abstract in English
The advance in the development of a vaccine against Plasmodium vivax requires the identification of immunodominant antigens able to induce a protective immune response against malaria. The present study evaluates the potential of the Merozoite Surface Protein 3 of P. vivax (PvMSP-3) as vaccine candidate. Recombinant proteins representing the C-terminal region of MSP-3α and different regions of MSP-3β (N and C-terminal and full-length protein) of P. vivax were used as antigen. The immunogenicity of these recombinants was evaluated in BALB/c mice using as adjuvant TLR agonists (FliC flagellin of Salmonella Typhimurium and CpG motif-containing DNA) or conventional adjuvants such as Aluminum hidroxide, Saponins, TiterMax Gold and Incomplete Freund's Adjuvant. The IgG antibodies were determined by ELISA in sera from mice two weeks after each immunizing dose. Our results demonstrated that MSP-3α and MSP-3β were able to induce high antibody titres in mice in the presence of different adjuvants, including TLR agonists. Among the tested formulations, the adjuvants CPG ODN 1826, Quil A, TiterMax and Incomplete Freund's Adjuvant were more immunogenic, therefore more promising for pre-clinical trials in non-human primates. Using TLR-4 KO mice, we demonstrated that the MSP-3β protein has an intrinsic adjuvant property that is independent of TLR4 and that contaminating LPS in the purified protein did not play any role in our system.
 
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Publishing Date
2012-02-06
 
WARNING: The material described below relates to works resulting from this thesis or dissertation. The contents of these works are the author's responsibility.
  • BITENCOURT, AMANDA R., et al. Antigenicity and Immunogenicity of Plasmodium vivax Merozoite Surface Protein-3 [doi:10.1371/journal.pone.0056061]. Plos One [online], 2013, vol. 8, p. e56061.
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