Abstract
BackgroundPlasmodium vivax merozoite surface protein-1 (MSP-1) is an antigen considered to be one of the leading malaria vaccine candidates. PvMSP-1 is highly immunogenic and evidences suggest that it is target for protective immunity against asexual blood stages of malaria parasites. Thus, this study aims to evaluate the acquired cellular and antibody immune responses against PvMSP-1 in individuals naturally exposed to malaria infections in a malaria-endemic area in the north-eastern Amazon region of Brazil.MethodsThe study was carried out in Paragominas, Pará State, in the Brazilian Amazon. Blood samples were collected from 35 individuals with uncomplicated malaria. Peripheral blood mononuclear cells were isolated and the cellular proliferation and activation was analysed in presence of 19 kDa fragment of MSP-1 (PvMSP-119) and Plasmodium falciparum PSS1 crude antigen. Antibodies IgE, IgM, IgG and IgG subclass and the levels of TNF, IFN-γ and IL-10 were measured by enzyme-linked immunosorbent assay.ResultsThe prevalence of activated CD4+ was greater than CD8+ T cells, in both ex-vivo and in 96 h culture in presence of PvMSP-119 and PSS1 antigen. A low proliferative response against PvMSP-119 and PSS1 crude antigen after 96 h culture was observed. High plasmatic levels of IFN-γ and IL-10 as well as lower TNF levels were also detected in malaria patients. However, in the 96 h supernatant culture, the dynamics of cytokine responses differed from those depicted on plasma assays; in presence of PvMSP-119 stimulus, higher levels of TNF were noted in supernatant 96 h culture of malaria patient’s cells while low levels of IFN-γ and IL-10 were verified. High frequency of malaria patients presenting antibodies against PvMSP-119 was evidenced, regardless class or IgG subclass.PvMSP-119-induced antibodies were predominantly on non-cytophilic subclasses.ConclusionsThe results presented here shows that PvMSP-119 was able to induce a high cellular activation, leading to production of TNF and emphasizes the high immunogenicity of PvMSP-119 in naturally exposed individuals and, therefore, its potential as a malaria vaccine candidate.
Highlights
Plasmodium vivax merozoite surface protein-1 (MSP-1) is an antigen considered to be one of the leading malaria vaccine candidates
Given the cumulative data supporting the potential of P. vivax merozoite surface protein-1 (PvMSP-1) as a malaria vaccine, and the substantial data generated through studies in human indicating that both humoral and cellular immune responses are needed to protect against malaria, the present study aims to evaluate the acquired cellular and antibody immune responses against PvMSP-119 in individuals naturally exposed to P. vivax or Plasmodium falciparum infections in a malaria-endemic area in the north-eastern Amazon region of Brazil
Written informed consent was obtained from all volunteer donors and 10 ml of venous blood samples were drawn in Vacutainer® EDTA tubes (Becton Dickinson, Oxnard, CA) from 35 individuals with uncomplicated malaria at the Hospital Municipal de Paragominas (HMP)
Summary
Plasmodium vivax merozoite surface protein-1 (MSP-1) is an antigen considered to be one of the leading malaria vaccine candidates. Since an effective malaria vaccine has long been envisaged as a potential tool for malaria control, two important points for its development are the identification of antigens that elicit the relevant immunological machinery and the correlation between the resulting immune system products and the clinical and/or parasitological protection induced. In this context, several antigens are being evaluated in clinical trials. One candidate vaccine is currently being assessed in Phase 3 clinical trials and approximately 20 others in Phase 1 or Phase 2 trials [1] Among these antigens, P. vivax merozoite surface protein-1 (PvMSP-1) is a promising candidate
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