Baculovirus merozoite surface protein 1 C-terminal recombinant antigens are highly protective in a natural primate model for human Plasmodium vivax malaria
Baculovirus merozoite surface protein 1 C-terminal recombinant antigens are highly protective in a natural primate model for human Plasmodium vivax malaria
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DOI：
10.1128/iai.66.4.1500-1506.1998
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发表时间：
1998-04-01
影响因子：
3.1
通讯作者：
Mendis, K
中科院分区：
文献类型：
--
作者：
Perera, KLRL;Handunnetti, SM;Mendis, K
这里报道了一项基于主要候选疫苗主要裂殖子表面抗原 1 (MSP1) 的成功抗血期疟疾疫苗试验，该试验基于食蟹猴疟原虫，这是一种灵长类疟疾寄生虫，与人类寄生虫间日疟原虫高度相似，在其自然宿主无边猴、中华猕猴中，两种重组杆状病毒表达的食蟹猴 MSP1与恶性疟原虫 MSP1 的 42-和 19-kDa C 端片段类似的蛋白质，通过用 p42、p19 或两者一起免疫三组三只动物进行测试。疫苗以 4 周间隔分三剂皮下递送，使用完全和不完全弗氏佐剂。通过酶联免疫吸附剂测量，获得了针对两种疫苗接种抗原的非常高的抗体滴度。测定（10（6）及以上）和通过间接免疫荧光测定（> 10（5））测量的整个寄生虫，在大多数动物中，从第一次到最后一次免疫增加了约10倍。用食蟹猴寄生虫进行的血液阶段攻击，在三只佐剂处理的动物和三只初始对照动物中导致血液感染，这种感染持续至少44天，达到峰值密度0.6和分别为 3.8%，相比之下，除了三个接种组中的九只动物中的一只之外，所有动物都受到高度保护，要么完全没有寄生虫血症，要么暂时性寄生虫血症仅持续 1 或 2 天，当 6 个月后对三只接种 p19 的猴子重新进行攻击时，保护功效没有改变。作为开发人间日疟原虫疟疾疫苗的替代系统，该疫苗基于间日疟原虫 MSP1 抗原的类似重组类似物。
A successful anti-blood stage malaria vaccine trial based on a leading vaccine candidate, the major merozoite surface antigen-1 (MSP1), is reported here, The trial was based on Plasmodium cynomolgi, which is a primate malaria parasite which is highly analogous to the human parasite Plasmodium vivax, in its natural host, the toque monkey, Macaca sinica, Two recombinant baculovirus-expressed P. cynomolgi MSP1 proteins, which are analogous to the 42- and 19-kDa C-terminal fragments of P.falciparum MSP1, were tested by immunizing three groups of three animals each with either p42, p19, or both together, The vaccines were delivered subcutaneously in three doses at 4-week intervals with complete and incomplete Freund's adjuvants, Very high antibody titers were obtained against both vaccinating antigens as measured by enzyme-linked immunosorbent assay (10(6) and above) and against whole parasites as measured by indirect immunofluorescence assay (>10(5)), achieving, in most animals, about a 10-fold increase from the first to the last immunization, A blood stage challenge with P. cynomolgi parasites led, in three adjuvant-treated and three naive control animals, to blood infections which were patent for at least 44 days, reaching peak densities of 0.6 and 3.8%, respectively, In contrast, all except one of the nine animals in the three vaccinated groups were highly protected, shelving either no parasitemia at all or transient parasitemias which were patent for only 1 or 2 days, When the three p19-vaccinated monkeys were rechallenged 6 months later, the protective efficacy was unchanged, The success of this trial, and striking analogies of this natural host-parasite system with human P. vivax malaria, suggests that it could serve as a surrogate system for the development of a human P, vivax malaria vaccine based on similar recombinant analogs of the P. vivax MSP1 antigen.