PROTECTION AGAINST MALARIA BY IMMUNIZATION WITH PLASMID DNA ENCODING CIRCUMSPOROZOITE PROTEIN
PROTECTION AGAINST MALARIA BY IMMUNIZATION WITH PLASMID DNA ENCODING CIRCUMSPOROZOITE PROTEIN
复制标题
DOI：
10.1073/pnas.91.21.9866
复制
发表时间：
1994-10-11
影响因子：
11.1
通讯作者：
HOFFMAN, SL
中科院分区：
文献类型：
--
作者：
SEDEGAH, M;HEDSTROM, R;HOFFMAN, SL
用辐照的孢子子免疫可以保护动物和人类免受疟疾的侵害，而环孢子子蛋白是这种保护性免疫的一个目标。我们现在报道，与使用辐照的孢子子免疫相比，将编码约氏疟原虫环孢子子蛋白的质粒DNA在小鼠肌肉内无佐剂注射可诱导更高水平的针对约氏疟原虫环孢子子蛋白的抗体和细胞毒性T淋巴细胞。用该疫苗免疫的小鼠在用5 × 10(5)个孢子虫（中位感染剂量bbb10(5)）攻毒后，肝脏期寄生虫负荷减少86%。接受两剂或三剂疫苗的28只小鼠中，有18只（68%）免受10(2)个孢子虫的攻击，这种保护依赖于CD8(+) T细胞。这些研究证明了质粒DNA免疫对非病毒性感染的效用。通过避免多肽合成、重组蛋白的表达和纯化以及佐剂的要求，这种免疫方法为快速鉴定保护性B和t细胞表位以及构建预防疟疾和其他传染病的疫苗提供了重要的替代方法。
Immunization with irradiated sporozoites protects animals and humans against malaria, and the circumsporozoite protein is a target of this protective immunity. We now report that adjuvant-free intramuscular injection of mice with plasmid DNA encoding the Plasmodium yoelii circumsporozoite protein induced higher levels of antibodies and cytotoxic T lymphocytes against the P. yoelii circumsporozoite protein than did immunization with irradiated sporozoites. Mice immunized with this vaccine had an 86% reduction in liver-stage parasite burden after challenge with 5 x 10(5) sporozoites (>10(5) median infectious doses). Eighteen (68%) of 28 mice that received two or three doses of vaccine were protected against challenge with 10(2) sporozoites, and the protection was dependent on CD8(+) T cells. These studies demonstrate the utility of plasmid DNA immunization against a nonviral infection. By obviating the requirement for peptide synthesis, expression and purification of recombinant proteins, and adjuvants, this method of immunization provides an important alternative for rapid identification of protective B- and T-cell epitopes and for construction of vaccines to prevent malaria and other infectious diseases.