Cellular and humoral immune responses against the Plasmodium vivax MSP-1(19) malaria vaccine candidate in individuals living in an endemic area in north-eastern Amazon region of Brazil

Abstract

Background: Plasmodium 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.Methods: the study was carried out in Paragominas, Para 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-1(19)) and Plasmodium falciparum PSS1 crude antigen. Antibodies IgE, IgM, IgG and IgG subclass and the levels of TNF, IFN-gamma and IL-10 were measured by enzyme-linked immunosorbent assay.Results: the prevalence of activated CD4(+) was greater than CD8(+) T cells, in both ex-vivo and in 96 h culture in presence of PvMSP-1(19) and PSS1 antigen. A low proliferative response against PvMSP-1(19) and PSS1 crude antigen after 96 h culture was observed. High plasmatic levels of IFN-gamma 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-1(19) stimulus, higher levels of TNF were noted in supernatant 96 h culture of malaria patient's cells while low levels of IFN-gamma and IL-10 were verified. High frequency of malaria patients presenting antibodies against PvMSP-1(19) was evidenced, regardless class or IgG subclass. PvMSP-1(19)-induced antibodies were predominantly on non-cytophilic subclasses.Conclusions: the results presented here shows that PvMSP-1(19) was able to induce a high cellular activation, leading to production of TNF and emphasizes the high immunogenicity of PvMSP-1(19) in naturally exposed individuals and, therefore, its potential as a malaria vaccine candidate.