A multiple antigen peptide (MAP) malaria vaccine containing minimal Plasmodium falciparum circumsporozoite protein repeat epitopes was assessed for safety and immunogenicity in volunteers of known class II genotypes. The MAP/alum/QS-21 vaccine formulation elicited high levels of parasite-specific antibodies in 10 of 12 volunteers expressing DQB1*0603, DRB1*0401, or DRB1*1101 class II molecules. In contrast, volunteers of other HLA genotypes were low responders or nonresponders. A second study of 7 volunteers confirmed the correlation of class II genotype and high responder phenotype. This is the first demonstration in humans that a peptide vaccine containing minimal T and B cell epitopes composed of only 5 amino acids (N, A, V, D, and P) can elicit antibody titers comparable to multiple exposures to irradiated P. falciparum—infected mosquitoes. Moreover, the high-responder phenotypes were predicted by analysis of peptide/HLA interactions in vitro, thus facilitating the rational design of epitope-based peptide vaccines for malaria, as well as for other pathogens.
在已知 II 类
基因型的志愿者中评估了含有最小恶性疟原虫周孢子虫蛋白重复表位的多抗原肽(
MAP)疟疾疫苗的安全性和免疫原性。在12名表达DQB1*0603、DRB1*0401或DRB1*1101 II类分子的志愿者中,有10名志愿者体内的
MAP/
明矾/QS-21疫苗配方激发了高
水平的寄生虫特异性
抗体。相比之下,其他 H
LA 基因型的志愿者反应较低或没有反应。对 7 名志愿者进行的第二项研究证实了 II 类
基因型与高应答表型的相关性。这是首次在人类中证明,一种包含仅由 5 个
氨基酸(N、A、V、D 和 P)组成的最小 T 细胞和 B 细胞表位的
多肽疫苗所激发的
抗体滴度可与多次暴露于经辐照的恶性疟原虫感染蚊子所激发的
抗体滴度相媲美。此外,通过分析肽与 H
LA 在体外的相互作用,可以预测高应答表型,从而有助于合理设计基于表位的
多肽疫苗,用于疟疾和其他病原体的治疗。