Induction of antigen-specific cytotoxic T lymphocytes in humans by a malaria DNA vaccine

Induction of antigen-specific cytotoxic T lymphocytes in humans by a malaria DNA vaccine
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DOI:
10.1126/science.282.5388.476
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发表时间:
1998-10-16
期刊:
影响因子:
56.9
通讯作者:
Hoffman, SL
Hoffman, SL
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Wang, RB;Doolan, DL;Hoffman, SL

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CD8(+)细胞毒性T淋巴细胞(CTL)对细胞内病原体的保护至关重要,但通常很难通过亚单位疫苗在动物体内诱导。DNA疫苗诱导保护性CD8(+)T细胞反应。未感染疟疾的志愿者接种了编码疟疾蛋白的质粒DNA,产生了抗原特异的、遗传受限的、依赖CD8(+)T细胞的CTL。反应是针对所有10个被测试的多肽,并受到6个人类淋巴细胞抗原(HL A)I类等位基因的限制。在健康的幼稚人类中首次证明了DNA疫苗诱导CD8(+)CTL,包括在同一个体中受多个HLA等位基因限制的CTL,为进一步的人体测试这一潜在的革命性疫苗技术提供了基础。
CD8(+) cytotoxic T lymphocytes (CTLs) are critical for protection against intracellular pathogens but often have been difficult to induce by subunit vaccines in animals. DNA vaccines elicit protective CD8(+) T cell responses. Malaria-naive volunteers who were vaccinated with plasmid DNA encoding a malaria protein developed antigen-specific, genetically restricted, CD8(+) T cell-dependent CTLs. Responses were directed against all 10 peptides tested and were restricted by six human lymphocyte antigen (HLA) class I alleles. This first demonstration in healthy naive humans of the induction of CD8(+) CTLs by DNA vaccines, including CTLs that were restricted by multiple HLA alleles in the same individual, provides a foundation for further human testing of this potentially revolutionary vaccine technology.