PDF(Pubmed)
Abstract：
BACKGROUND: Plasmodium vivax represents the most geographically widespread human malaria parasite affecting civilian and military populations in endemic areas. Targeting the pre-erythrocytic (PE) stage of the parasite life cycle is especially appealing for developing P. vivax vaccines as it would prevent disease and transmission. Here, naturally acquired immunity to a panel of P. vivax PE antigens was explored, which may facilitate vaccine development and lead to a better understanding of naturally acquired PE immunity.
METHODS: Twelve P. vivax PE antigens orthologous to a panel of P. falciparum antigens previously identified as highly immunogenic in protected subjects after immunization with radiation attenuated sporozoites (RAS) were used for evaluation of humoral and cellular immunity by ELISA and IFN-γ ELISpot. Samples from P. vivax infected individuals (n = 76) from a low endemic malaria region in the Peruvian Amazon Basin were used.
RESULTS: In those clinical samples, all PE antigens evaluated showed positive IgG antibody reactivity with a variable prevalence of 58-99% in recently P. vivax diagnosed patients. The magnitude of the IgG antibody response against PE antigens was lower compared with blood stage antigens MSP1 and DBP-II, although antibody levels persisted better for PE antigens (average decrease of 6% for PE antigens and 43% for MSP1, p < 0.05). Higher IgG antibodies was associated with one or more previous malaria episodes only for blood stage antigens (p < 0.001). High IgG responders across PE and blood stage antigens showed significantly lower parasitaemia compared to low IgG responders (median 1,921 vs 4,663 par/µl, p < 0.05). In a subgroup of volunteers (n = 17),positive IFN-γ T cell response by ELISPOT was observed in 35% vs 9-35% against blood stage MSP1 and PE antigens, respectively, but no correlation with IgG responses.
CONCLUSIONS: These results demonstrate clear humoral and T cell responses against P. vivax PE antigens in individuals naturally infected with P. vivax. These data identify novel attractive PE antigens suitable for use in the potential development and selection of new malaria vaccine candidates which can be used as a part of malaria prevention strategies in civilian and military populations living in P. vivax endemic areas.
METHODS: Twelve P. vivax PE antigens orthologous to a panel of P. falciparum antigens previously identified as highly immunogenic in protected subjects after immunization with radiation attenuated sporozoites (RAS) were used for evaluation of humoral and cellular immunity by ELISA and IFN-γ ELISpot. Samples from P. vivax infected individuals (n = 76) from a low endemic malaria region in the Peruvian Amazon Basin were used.
RESULTS: In those clinical samples, all PE antigens evaluated showed positive IgG antibody reactivity with a variable prevalence of 58-99% in recently P. vivax diagnosed patients. The magnitude of the IgG antibody response against PE antigens was lower compared with blood stage antigens MSP1 and DBP-II, although antibody levels persisted better for PE antigens (average decrease of 6% for PE antigens and 43% for MSP1, p < 0.05). Higher IgG antibodies was associated with one or more previous malaria episodes only for blood stage antigens (p < 0.001). High IgG responders across PE and blood stage antigens showed significantly lower parasitaemia compared to low IgG responders (median 1,921 vs 4,663 par/µl, p < 0.05). In a subgroup of volunteers (n = 17),positive IFN-γ T cell response by ELISPOT was observed in 35% vs 9-35% against blood stage MSP1 and PE antigens, respectively, but no correlation with IgG responses.
CONCLUSIONS: These results demonstrate clear humoral and T cell responses against P. vivax PE antigens in individuals naturally infected with P. vivax. These data identify novel attractive PE antigens suitable for use in the potential development and selection of new malaria vaccine candidates which can be used as a part of malaria prevention strategies in civilian and military populations living in P. vivax endemic areas.
摘要：
背景：间日疟原虫是地理上最广泛的人类疟疾寄生虫，影响流行地区的平民和军事人群。靶向寄生虫生命周期的前红细胞（PE）阶段对于开发间日疟原虫疫苗尤其有吸引力，因为它可以预防疾病和传播。这里,对一组间日疟原虫PE抗原的自然获得性免疫进行了探索，这可能有助于疫苗的开发，并导致更好地了解自然获得性PE免疫。
方法:与先前在用辐射减毒子孢子(RAS)免疫后在受保护的受试者中鉴定为高度免疫原性的一组恶性疟原虫抗原的12种间日疟原虫PE抗原用于通过ELISA和IFN-γELISpot评估体液和细胞免疫。使用来自秘鲁亚马逊盆地低地方性疟疾地区的间日疟原虫感染个体(n=76)的样品。
结果：在这些临床样本中，在最近诊断为间日疟原虫的患者中,所有评估的PE抗原均显示IgG抗体反应性阳性,可变患病率为58-99%.与血液阶段抗原MSP1和DBP-II相比，针对PE抗原的IgG抗体应答的幅度较低，尽管PE抗原的抗体水平持续较好（PE抗原平均下降6％，MSP1平均下降43％，p<0.05）。较高的IgG抗体仅与血液阶段抗原有关（p<0.001）。与低IgG应答者相比，PE和血液阶段抗原的高IgG应答者显示出显著较低的寄生虫血症（中位数1,921比4,663par/µl，p<0.05)。在志愿者亚组(n=17)中，通过ELISPOT的阳性IFN-γT细胞应答在35％和9-35％的血液阶段MSP1和PE抗原中观察到，分别,但与IgG反应无关。
结论：这些结果证明了在自然感染间日疟原虫的个体中针对间日疟原虫PE抗原的明显体液和T细胞应答。这些数据确定了新的有吸引力的PE抗原，适用于潜在开发和选择新的疟疾疫苗候选物，这些候选物可以用作生活在间日疟原虫流行地区的平民和军事人群的疟疾预防策略的一部分。
方法:与先前在用辐射减毒子孢子(RAS)免疫后在受保护的受试者中鉴定为高度免疫原性的一组恶性疟原虫抗原的12种间日疟原虫PE抗原用于通过ELISA和IFN-γELISpot评估体液和细胞免疫。使用来自秘鲁亚马逊盆地低地方性疟疾地区的间日疟原虫感染个体(n=76)的样品。
结果：在这些临床样本中，在最近诊断为间日疟原虫的患者中,所有评估的PE抗原均显示IgG抗体反应性阳性,可变患病率为58-99%.与血液阶段抗原MSP1和DBP-II相比，针对PE抗原的IgG抗体应答的幅度较低，尽管PE抗原的抗体水平持续较好（PE抗原平均下降6％，MSP1平均下降43％，p<0.05）。较高的IgG抗体仅与血液阶段抗原有关（p<0.001）。与低IgG应答者相比，PE和血液阶段抗原的高IgG应答者显示出显著较低的寄生虫血症（中位数1,921比4,663par/µl，p<0.05)。在志愿者亚组(n=17)中，通过ELISPOT的阳性IFN-γT细胞应答在35％和9-35％的血液阶段MSP1和PE抗原中观察到，分别,但与IgG反应无关。
结论：这些结果证明了在自然感染间日疟原虫的个体中针对间日疟原虫PE抗原的明显体液和T细胞应答。这些数据确定了新的有吸引力的PE抗原，适用于潜在开发和选择新的疟疾疫苗候选物，这些候选物可以用作生活在间日疟原虫流行地区的平民和军事人群的疟疾预防策略的一部分。
