de Oliveira G A, Clavijo P, Nussenzweig R S, Nardin E H
Department of Medical and Molecular Parasitology, New York University School of Medicine, NY 10010.
Vaccine. 1994 Aug;12(11):1012-7. doi: 10.1016/0264-410x(94)90337-9.
Multiple-antigen peptides (MAPs), containing B- and T-cell epitopes of the Plasmodium falciparum circumsporozoite (CS) protein, have been designed to overcome the limitations of first-generation peptide vaccines caused by low epitope density, carrier toxicity and the lack of parasite-derived T-cell epitopes. The immunogenicity of a P. falciparum MAP construct (T1B4), containing four copies of the 5' repeat cell T epitope (T1) combined with the 3' repeat epitope (NANP)3, has been examined using different adjuvant formulations. Mice immunized intraperitoneally or subcutaneously with (T1B)4 in alum, a formulation suitable for human vaccines, developed high anti-peptide and anti-sporozoite antibody titres, comparable with those obtained with Freund's adjuvant. The MAP/alum formulation also elicited a strong anamnestic antibody response in sporozoite-primed mice, raising the possibility of using a MAP/alum vaccine to increase the low anti-sporozoite antibody levels of people living in malaria-endemic areas.
已设计出包含恶性疟原虫环子孢子蛋白(CS)的B细胞和T细胞表位的多抗原肽(MAPs),以克服第一代肽疫苗因表位密度低、载体毒性以及缺乏寄生虫衍生的T细胞表位而产生的局限性。使用不同的佐剂配方检测了一种包含四个5'重复细胞T表位(T1)拷贝与3'重复表位(NANP)3结合的恶性疟原虫MAP构建体(T1B4)的免疫原性。用适用于人类疫苗的明矾中的(T1B)4对小鼠进行腹腔内或皮下免疫,产生了高抗肽和抗子孢子抗体滴度,与使用弗氏佐剂获得的滴度相当。MAP/明矾配方还在子孢子致敏的小鼠中引发了强烈的回忆性抗体反应,增加了使用MAP/明矾疫苗提高疟疾流行地区人群低抗子孢子抗体水平的可能性。