Soares I S, Levitus G, Souza J M, Del Portillo H A, Rodrigues M M
Departamento de Patologia, Centro de Ciências Biológicas, Universidade Federal do Pará, Brazil.
Infect Immun. 1997 May;65(5):1606-14. doi: 10.1128/iai.65.5.1606-1614.1997.
In this study, we evaluated the naturally acquired immune response to Plasmodium vivax merozoite surface protein 1 (PvMSP1) in individuals with recent clinical episodes of malaria from the state of Para, Brazil. Ten recombinant proteins representing the first 682 amino acids (aa) of the N-terminal region and one representing the final 111 aa of the C-terminal region were expressed in Escherichia coli as glutathione S-transferase fusion proteins. Both of these regions have been suggested as candidates for development of a vaccine against Plasmodium sp. The total frequencies of individuals with antibodies and cellular immune responses to PvMSP1 were high (83.8 and 75%, respectively). The recombinant proteins representing the N- and C-terminal regions were recognized by 51.4 and 64.1% of sera, respectively. The frequency of responders to the C-terminal region increased according to the number of previous malaria episodes, reaching 83.3% after four episodes. Cellular immune response was measured by in vitro proliferation and gamma interferon production. Peripheral blood mononuclear cells of 75 and 47.2% of individuals proliferated in response to stimulation by the N- and C-terminal regions, respectively. Also, we found that one protein representing the N terminus and a second representing the C terminus of PvMSP1 stimulated 54.5% of individuals to secrete gamma interferon. We concluded that PvMSP1 is immunogenic to a large proportion of individuals exposed to malaria. Our results also suggested that the C-terminal region of PvMSP1 containing the two epidermal growth factor-like domains is particularly immunogenic to antibodies and T cells during natural infection in humans.
在本研究中,我们评估了巴西帕拉州近期有疟疾临床发作的个体对间日疟原虫裂殖子表面蛋白1(PvMSP1)的自然获得性免疫反应。在大肠杆菌中表达了代表N端区域前682个氨基酸(aa)的10种重组蛋白以及代表C端区域最后111个aa的1种重组蛋白,作为谷胱甘肽S-转移酶融合蛋白。这两个区域均被认为是开发抗疟原虫疫苗的候选区域。对PvMSP1产生抗体和细胞免疫反应的个体总频率很高(分别为83.8%和75%)。代表N端和C端区域的重组蛋白分别被51.4%和64.1%的血清识别。对C端区域有反应者的频率根据既往疟疾发作次数增加,四次发作后达到83.3%。通过体外增殖和γ干扰素产生来测量细胞免疫反应。分别有75%和47.2%的个体外周血单个核细胞在受到N端和C端区域刺激后发生增殖。此外,我们发现一种代表PvMSP1 N端的蛋白和另一种代表C端的蛋白刺激54.5%的个体分泌γ干扰素。我们得出结论,PvMSP1对很大一部分接触过疟疾的个体具有免疫原性。我们的结果还表明,在人类自然感染期间,PvMSP1含有两个表皮生长因子样结构域的C端区域对抗体和T细胞具有特别的免疫原性。