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选择不同株恶性疟原虫用于在南美白狨猴中测试血液阶段疫苗。

Selection of different strains of Plasmodium falciparum for testing blood-stage vaccines in Aotus nancymai monkeys.

作者信息

Collins W E, Galland G G, Sullivan J S, Morris C L

机构信息

Division of Parasitic Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.

出版信息

Am J Trop Med Hyg. 1994 Aug;51(2):224-32. doi: 10.4269/ajtmh.1994.51.224.

DOI:10.4269/ajtmh.1994.51.224
PMID:8074257
Abstract

Three strains of Plasmodium falciparum, Vietnam Oak Knoll (FVO), Uganda Palo Alto (Hawaii) (FUP-H) and Uganda Palo Alto (Cayenne) (FUP-C), were examined in 154 Aotus nancymai monkeys as suitable models for testing blood-stage vaccines. The Vietnam Oak Knoll strain had the greatest number of animals with maximum parasite counts > 200,000/microliters. Uniformity of the parasitemia curve increased from passage 4 to passage 6 with an accompanying decrease in the number of days required to reach maximum parasitemia or required treatment. The Uganda Palo Alto (Hawaii) strain was highly infectious, but many animals had extended prepatent periods and extended days to maximum parasitemia. The FUP-H strain would require a greater number of animals per test group to detect partial protection because of the greater number of low-density maximum parasite counts in control animals. The Uganda Palo Alto (Cayenne) strain was poorly adapted to intact A. nancymai. However, five of six splenectomized monkeys inoculated during passage 6 with 10(5) parasites had maximum parasite counts > 200,000/microliters. For the testing of vaccines against primary parasitemia in the A. nancymai model system, the FVO at passage 4 level would appear preferable to passage 6 parasites following a challenge with 10(5) parasites. A similar pattern could be obtained using FUP-H if the challenge was 10(6) parasites. To measure immune memory against recrudescence or rechallenge infection, FUP-C at an early passage in splenectomized A. nancymai would appear to be the appropriate model.

摘要

对三种恶性疟原虫菌株,即越南奥克诺尔株(FVO)、乌干达帕洛阿尔托株(夏威夷)(FUP-H)和乌干达帕洛阿尔托株(卡宴)(FUP-C),在154只南希夜猴中进行了检测,作为测试血液阶段疫苗的合适模型。越南奥克诺尔株中寄生虫计数最大值>200,000/微升的动物数量最多。从第4代到第6代,寄生虫血症曲线的一致性增加,同时达到最大寄生虫血症或需要治疗所需的天数减少。乌干达帕洛阿尔托株(夏威夷)具有高度传染性,但许多动物的潜伏期延长,达到最大寄生虫血症的天数也延长。由于对照动物中低密度最大寄生虫计数较多,FUP-H株每个测试组需要更多动物来检测部分保护作用。乌干达帕洛阿尔托株(卡宴)对完整的南希夜猴适应性较差。然而,在第6代接种10⁵个寄生虫的6只脾切除猴子中有5只的寄生虫计数最大值>200,000/微升。在南希夜猴模型系统中测试针对原发性寄生虫血症的疫苗时,在接种10⁵个寄生虫后,第4代水平的FVO似乎比第6代寄生虫更可取。如果接种10⁶个寄生虫,使用FUP-H也可获得类似模式。为了测量针对复发或再次感染的免疫记忆,在脾切除的南希夜猴中早期传代的FUP-C似乎是合适的模型。

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