首页> 外文期刊>Infection and immunity >Vaccine Efficacy of Recombinant Plasmodium falciparumMerozoite Surface Protein 1 in Malaria-Naive, -Exposed, and/or -Rechallenged Aotus vociferans Monkeys
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Vaccine Efficacy of Recombinant Plasmodium falciparumMerozoite Surface Protein 1 in Malaria-Naive, -Exposed, and/or -Rechallenged Aotus vociferans Monkeys

机译:重组疟原虫恶性疟原虫表面蛋白1在未患疟疾,暴露和/或受挑战的沃克沃提斯猴中的疫苗功效

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Protection against a lethal challenge infection of Plasmodium falciparum was elicited in malaria-naive Aotus vociferans monkeys by vaccination with the C terminus 19-kDa protein of the major merozoite surface protein (MSP-119) fused to tetanus toxoid universal T-cell epitopes P30 and P2. Three of four monkeys were protected against a 104-parasite challenge. Four monkeys were challenged with 105 parasites; one self-cured the infection, two were protected against high parasitemia (42to MSP-133 and MSP-119. To mimic the repeated reinfections seen in regions where malaria is endemic, a second malaria parasite challenge was administered 4 months later. All P30P2MSP-119-vaccinated monkeys were protected; thus, a single challenge infection may underestimate vaccine efficacy. ELISA antibody titers correlated with protection against a second infection but had decreased compared to the first challenge. As most target populations for asexual blood-stage malaria vaccines will have been exposed to malaria parasites, a malaria parasite-exposed monkey was vaccinated with P30P2MSP-119. This monkey was completely protected, while a malaria parasite-naive P30P2MSP-119-vaccinated monkey self-cured a low-grade parasitemia. Prior malaria parasite infection primed the production of anti-native MSP-119 antibodies, which were boosted by vaccination with recombinant P30P2MSP-119. Preliminary data suggest that immunogenicity studies of vaccines designed for malaria parasite-exposed populations should also be conducted in malaria parasite-exposed subjects.
机译:通过接种与破伤风类毒素通用T细胞抗原决定簇P30和P2。四只猴子中的三只受到了104寄生虫攻击的保护。四只猴子受到105种寄生虫的攻击;一种是自治愈的​​感染,两种是针对高寄生虫病的保护(针对MSP-133和MSP-119的是42。为了模仿在疟疾流行地区反复出现的再感染,在4个月后进行了第二次疟原虫挑战。所有P30P2MSP- 119位接种过疫苗的猴子受到保护;因此,一次攻击感染可能会低估疫苗的效力; ELISA抗体滴度与对第二次感染的保护作用相关,但与第一次攻击相比有所降低,因为大多数无性血液阶段疟疾疫苗的目标人群都会在暴露于疟原虫的情况下,向暴露于疟原虫的猴子接种了P30P2MSP-119,这只猴子受到了完全保护,而未接种疟原虫的P30P2MSP-119接种的猴子自我治愈了低度寄生虫病。最初的抗MSP-119抗体的生产已经启动,而重组P30P2MSP-119的疫苗接种增强了该抗体的生产。还应在接触疟原虫的受试者中进行针对疟原虫接触人群设计的疫苗的免疫原性研究。

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