Egan A F, Blackman M J, Kaslow D C
Malaria Vaccines Section, Malaria Vaccine Development Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Infect Immun. 2000 Mar;68(3):1418-27. doi: 10.1128/IAI.68.3.1418-1427.2000.
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-1(19)) fused to tetanus toxoid universal T-cell epitopes P30 and P2. Three of four monkeys were protected against a 10(4)-parasite challenge. Four monkeys were challenged with 10(5) parasites; one self-cured the infection, two were protected against high parasitemia (<2%) but were treated for severe anemia (hematocrit of <25%), and the fourth was not protected. In this model system, anemia appears to be a manifestation of incomplete protection (prolonged low-level parasitemia). Enzyme-linked immunosorbent assay (ELISA) antibody titers correlated with protection. Antibodies from some protected monkeys inhibited secondary processing of MSP-1(42) to MSP-1(33) and MSP-1(19). To mimic the repeated reinfections seen in regions where malaria is endemic, a second malaria parasite challenge was administered 4 months later. All P30P2MSP-1(19)-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-1(19). This monkey was completely protected, while a malaria parasite-naive P30P2MSP-1(19)-vaccinated monkey self-cured a low-grade parasitemia. Prior malaria parasite infection primed the production of anti-native MSP-1(19) antibodies, which were boosted by vaccination with recombinant P30P2MSP-1(19). Preliminary data suggest that immunogenicity studies of vaccines designed for malaria parasite-exposed populations should also be conducted in malaria parasite-exposed subjects.
通过接种与破伤风类毒素通用T细胞表位P30和P2融合的主要裂殖子表面蛋白（MSP-1(19)）的C末端19-kDa蛋白，在未感染过疟疾的夜猴（Aotus vociferans）中引发了针对恶性疟原虫致死性攻击感染的保护作用。四只猴子中有三只在受到10⁴个疟原虫攻击时得到了保护。四只猴子受到10⁵个疟原虫的攻击；一只自行治愈了感染，两只免受高寄生虫血症（<2%）但因严重贫血（血细胞比容<25%）而接受治疗，第四只未得到保护。在这个模型系统中，贫血似乎是不完全保护（长期低水平寄生虫血症）的一种表现。酶联免疫吸附测定（ELISA）抗体滴度与保护作用相关。一些受保护猴子的抗体抑制了MSP-1(42)向MSP-1(33)和MSP-1(19)的二次加工。为模拟疟疾流行地区所见的反复再感染，4个月后进行了第二次疟原虫攻击。所有接种P30P2MSP-1(19)的猴子都受到了保护；因此，单次攻击感染可能会低估疫苗效力。ELISA抗体滴度与针对第二次感染的保护作用相关，但与第一次攻击相比有所下降。由于无性血液期疟疾疫苗的大多数目标人群都曾接触过疟原虫，一只接触过疟原虫的猴子接种了P30P2MSP-1(19)。这只猴子得到了完全保护，而一只未感染过疟原虫的接种P30P2MSP-1(19)的猴子自行治愈了低度寄生虫血症。先前的疟原虫感染引发了抗天然MSP-1(19)抗体的产生，通过接种重组P30P2MSP-1(19)使其得到增强。初步数据表明，为接触过疟原虫的人群设计的疫苗的免疫原性研究也应在接触过疟原虫的受试者中进行。
