Herrera S, Herrera M A, Perlaza B L, Burki Y, Caspers P, Döbeli H, Rotmann D, Certa U
Department of Microbiology, School of Health, Universidad del Valle, Cali, Colombia.
Proc Natl Acad Sci U S A. 1990 May;87(10):4017-21. doi: 10.1073/pnas.87.10.4017.
The current spread of multidrug-resistant malaria demands rapid vaccine development against the major pathogen Plasmodium falciparum. The high quantities of protein required for a worldwide vaccination campaign select recombinant DNA technology as a practical approach for large-scale antigen production. We describe the vaccination of Aotus monkeys with two recombinant blood-stage antigens (recombinant p41 and 190N) that were considered as vaccine candidates because parasite-derived antigen preparations could protect susceptible monkeys from an otherwise lethal malaria infection. In contrast to the natural antigen, recombinant p41 protein (P. falciparum aldolase) could not protect monkeys, although all animals seroconverted. 190N antigen, a recombinant protein containing conserved sequences of the major merozoite surface antigen p190, protected two of five monkeys from critical levels of infection with the highly virulent FVO isolate of P. falciparum. However, the B- and T-cell responses to 190N antigen were similar in protected and unprotected animals so that other unknown factors may contribute to protection. Higher purity or lack of protective epitopes or different structure of protective epitopes in the recombinant proteins might explain the better performance of parasite-derived antigens in vaccination trials. The partial protection obtained with 190N antigen suggests that this molecule could contribute to a vaccine mixture against P. falciparum.
耐多药疟疾的当前传播态势要求迅速研发针对主要病原体恶性疟原虫的疫苗。全球疫苗接种运动所需的大量蛋白质使得重组DNA技术成为大规模生产抗原的实用方法。我们描述了用两种重组血液期抗原（重组p41和190N）对夜猴进行疫苗接种的情况，这两种抗原被视为疫苗候选物，因为源自寄生虫的抗原制剂可以保护易感猴子免受原本致命的疟疾感染。与天然抗原不同，重组p41蛋白（恶性疟原虫醛缩酶）虽然所有动物都发生了血清转化，但却无法保护猴子。190N抗原是一种包含主要裂殖子表面抗原p190保守序列的重组蛋白，保护了五只猴子中的两只免受恶性疟原虫高毒力FVO分离株的严重感染。然而，受保护和未受保护动物对190N抗原的B细胞和T细胞反应相似，因此其他未知因素可能有助于提供保护。重组蛋白中更高的纯度、缺乏保护性表位或保护性表位的不同结构可能解释了源自寄生虫的抗原在疫苗试验中表现更好的原因。用190N抗原获得的部分保护表明该分子可能有助于组成针对恶性疟原虫的疫苗混合物。
