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Abstract. A parasitophorous vacuole protein of Plasmodium falciparum, p126, is a potential candidate for a malaria vaccine. Its N-terminal region, composed of six repeats of eight amino acids, appears to be involved in the induction of protective immunity against P. falciparum challenge in monkeys. This study evaluated the immune response to p126 and to its N-terminal region (Nt47) in patients (n ϭ 45) living in a malaria-endemic area of Brazil (Colina, Porto Velho, Rondonia). Cellular proliferative responses against Nt47 were low and infrequent. The study of the humoral immune response demonstrated that 95% of the patients had detectable anti-p126 antibodies and 77% had anti-Nt47 antibodies. Analysis of the antibody isotypes specific for Nt47 revealed that all four IgG subclasses were present and individuals with higher levels of anti-Nt47 cytophilic IgG antibody (IgG1 ϩ IgG3/IgG2 ϩ IgG4) had significantly lower parasitemia levels, suggesting that antibodies to the N-terminal region of the p126 protein may contribute to acquisition of immunity to P. falciparum malaria.The Plasmodium falciparum p126 antigen 1 is synthesized by the parasite between the 32nd and the 36th hr of a 42-hr erythrocytic cycle, then stored inside the parasitophorous vacuole. This antigen is processed into fragments of 50 and 73 kD, the latter one composed of two peptides of 47 and 18 kD linked by disulfide bridges. This processing is associated with the release of merozoites from mature schizonts. 2 The p126 protein, also known as serine-rich antigen 3 or serine-rich protein 4 based on the similarity of coding genes, ranks as a candidate antigen for inclusion in a subunit vaccine to control the asexual erythrocytic phase of P. falciparum malaria for the following reasons: 1) it is antigenically conserved among different strains of P. falciparum; 5 2) monoclonal and polyclonal antibodies specific for p126 inhibit the in vitro growth of the parasite; 6-9 and 3) it can induce partial protection against parasite challenge in various species of monkeys. 1,3,[10][11][12] Moreover, the N-terminal portion (located at the amino-terminal end of the 47-kD subfragment) is involved in the induction of this protective immunity. 13,14 In view of these encouraging results, we focused on the six repeats of eight amino acids at the N-terminal end of the molecule 15 (Nt47) since this domain 1) includes a B and T cell epitope recognized by infected humans 16 (Roussilhon C, unpublished data); and 2) is the only one of the C-and Nterminal regions of the processed fragments of p126 that is able to induce an antibody response in mice immunized with respective peptides. 17 However, mice did not develop antibodies against this domain of the molecule when immunized with schizont-infected erythrocytes. 16 It is therefore of great value for vaccine design to determine the degree of immunogenicity of the Nt47 domain in humans living in a malaria-endemic area and naturally exposed to plasmodial antigens. In this respect, we investigated the immune response to Nt47 an...

The goal of this study was to evaluate the antibody response induced by Plasmodium falciparum glutamate-rich protein (GLURP) in naturally exposed individuals from the Brazilian Amazon region (Rondonia State). The results showed that most individuals had IgG against two well-defined regions within P. falciparum GLURP, the relatively conserved N-terminal nonrepeat region (R0) and the immunodominant repeat region (R2), 67% and 79%, respectively. The peptides S4 from R2 (53%) and P11 from R0 (49%) were identified as immunodominant B cell epitopes and induced higher levels of antibodies. The number of GLURP peptides recognized and the levels of IgG against S4 and P11 peptides showed a positive correlation with age and time of exposure in the malaria-endemic area studied. The antibody responses against GLURP epitopes appear to be modulated by HLA class II antigens. Interestingly, the GLURP immunodominant B cell epitopes in individuals from a Brazilian malaria-endemic area are distinguishable from those of the African malaria-endemic area. Considering the importance of GLURP as a malaria vaccine candidate and the increasing focus on the use of subunit vaccines in the control of infectious diseases, the concern of the influence of class II allele frequencies in ethnically diverse populations may be important before vaccine trials are conducted among people naturally exposed to malaria parasites.

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.