Freidag Brenda L, Mendez Susana, Cheever Allen W, Kenney Richard T, Flynn Barbara, Sacks David L, Seder Robert A
Cellular Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Exp Parasitol. 2003 Mar-Apr;103(3-4):160-8. doi: 10.1016/s0014-4894(03)00099-7.
Cutaneous leishmaniasis, a parasitic infection causing ulcerating skin lesions, is an important disease worldwide and urgently requires a vaccine. Animal models that closely mimic human disease are essential for designing preventive vaccines against Leishmania major. We have evaluated both biologic and immunologic parameters of cutaneous L. major infection in nonhuman primates. Naïve rhesus macaques or monkeys previously exposed to L. major were infected with varying doses of L. major metacyclic promastigotes, and lesion size was assessed over a 10-week period. Monkeys previously infected with L. major had much smaller lesions that resolved faster compared with those of naïve monkeys in response to the two higher doses of infection. Moreover, eight of nine naïve monkeys had parasites detected in their lesions during the course of the infection. In addition, the cellular infiltrate within the lesions was qualitatively and quantitatively different in naïve versus previously infected monkeys. Finally, an ELIspot assay determined that the magnitude and kinetics of responses differed between previously infected and naïve monkeys.
皮肤利什曼病是一种由寄生虫感染引起的皮肤溃疡性疾病,在全球范围内都是一种重要疾病,迫切需要一种疫苗。对于设计针对硕大利什曼原虫的预防性疫苗而言,能密切模拟人类疾病的动物模型至关重要。我们已经评估了非人灵长类动物皮肤感染硕大利什曼原虫后的生物学和免疫学参数。将未感染过的恒河猴或先前接触过硕大利什曼原虫的猴子用不同剂量的硕大利什曼原虫循环前鞭毛体进行感染,并在10周的时间内评估皮损大小。与未感染过的猴子相比,先前感染过硕大利什曼原虫的猴子在接受两种较高剂量感染后,皮损要小得多,愈合也更快。此外,在感染过程中,九只未感染过的猴子中有八只在其皮损中检测到了寄生虫。另外,未感染过与先前感染过的猴子皮损内的细胞浸润在定性和定量方面均有所不同。最后,一项酶联免疫斑点试验确定,先前感染过的猴子与未感染过的猴子之间的反应强度和动力学有所不同。