Moreno C A, Rodriguez R, Oliveira G A, Ferreira V, Nussenzweig R S, Moya Castro Z R, Calvo-Calle J M, Nardin E
Instituto de Inmunología, Hospital San Juan de Dios, Santafé de Bogotá, Colombia.
Vaccine. 1999 Aug 20;18(1-2):89-99. doi: 10.1016/s0264-410x(99)00184-x.
Multiple antigen peptides (MAPs) containing epitopes of the major surface protein of the malaria sporozoite, the circumsporozoite (CS) protein, have been shown in previous studies to elicit antibody-mediated protection against sporozoite challenge in experimental murine and simian hosts. For the preparation for a phase I trial of a P. falciparum (T1B)4 MAP, which contains T and B cell epitopes from the CS repeat region, pre-clinical immunogenicity and adjuvant formulation studies were carried out in mice and Aotus monkeys. The (T1B)4 MAP was found to be immunogenic in three different species of owl monkeys, Aotus nancymae, A. vociferans and A. nigriceps. Optimal antibody responses were obtained in A. nancymae immunized s.c. with (T1B)4 MAP emulsified in Freund's, in which peak titers of over 10(6) were obtained in individual monkeys. MAP immunized A. vociferans also developed high levels of anti-sporozoite antibodies, although the kinetics and the magnitude of the response differed from A. nancymae. (T1B)4 MAP adsorbed to alum (aluminum hydroxide), a formulation that is acceptable for human use, was less immunogenic in naive A. nancymae, as well as A. nigriceps. The injection of MAPs/alum, however, significantly enhanced antibody responses in sporozoite-primed monkeys, suggesting that the administration of the MAP vaccine may be an effective means to increase the low levels of antibody present in individuals living in malaria endemic areas. The addition of a co-adjuvant QS-21, a purified saponin, significantly increased the immunogenicity of the alum-adsorbed MAP in both mice and monkeys, providing a vaccine formulation suitable for phase I trials in human volunteers.
含有疟原虫子孢子主要表面蛋白环子孢子（CS）蛋白表位的多抗原肽（MAPs），在先前的研究中已表明，在实验性鼠类和猿类宿主中可引发抗体介导的针对子孢子攻击的保护作用。为制备含有来自CS重复区域的T细胞和B细胞表位的恶性疟原虫（T1B）4 MAP进行I期试验，在小鼠和夜猴中开展了临床前免疫原性和佐剂配方研究。发现（T1B）4 MAP在三种不同的夜猴物种——南希夜猴、叫夜猴和黑首夜猴中具有免疫原性。用弗氏佐剂乳化的（T1B）4 MAP经皮下免疫南希夜猴可获得最佳抗体反应，其中个别猴子的峰值滴度超过10⁶。用MAP免疫的叫夜猴也产生了高水平的抗子孢子抗体，尽管反应的动力学和强度与南希夜猴不同。吸附于明矾（氢氧化铝）的（T1B）4 MAP（一种可用于人类的配方），在未接触过抗原的南希夜猴以及黑首夜猴中免疫原性较低。然而，注射MAPs/明矾可显著增强经子孢子致敏的猴子的抗体反应，这表明给予MAP疫苗可能是提高生活在疟疾流行地区个体中低水平抗体的有效手段。添加共佐剂QS - 21（一种纯化的皂苷）可显著提高明矾吸附的MAP在小鼠和猴子中的免疫原性，从而提供一种适合人类志愿者I期试验的疫苗配方。
