Hanke T, Schneider J, Gilbert S C, Hill A V, McMichael A
Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, UK.
Vaccine. 1998 Feb;16(4):426-35. doi: 10.1016/s0264-410x(97)00296-x.
The potential of building multi-cytotoxic T lymphocyte (CTL) epitope antigens in combination with the nucleic acid immunization technology is explored for development of acquired immunodeficiency syndrome (AIDS) and malaria vaccines. A novel minimal vector pTH for direct gene transfer was constructed for efficient expression of vaccine antigens and used as a vehicle for human immunodeficiency virus (HIV)- and Plasmodium falciparum-derived polyepitope genes. Two murine epitopes were included into these constructs to allow for testing of vaccine immunogenicity in small animals. The results showed that a single DNA injection generated CTL responses in all 15 vaccinated mice. The elicited CTL precursor frequencies were estimated in an interferon-gamma (IFN-gamma)-based ELISPOT assay and found to be an average of 300 (range 4-1346) peptide-responding cells per 10(6) splenocytes.
为开发获得性免疫缺陷综合征(艾滋病)和疟疾疫苗,探索了构建多细胞毒性T淋巴细胞(CTL)表位抗原并结合核酸免疫技术的潜力。构建了一种新型最小载体pTH用于直接基因转移,以高效表达疫苗抗原,并用作携带人类免疫缺陷病毒(HIV)和恶性疟原虫来源的多表位基因的载体。这些构建体中包含两个鼠表位,以便在小动物中测试疫苗的免疫原性。结果显示,单次DNA注射在所有15只接种疫苗的小鼠中均产生了CTL反应。通过基于γ干扰素(IFN-γ)的ELISPOT试验估计诱导的CTL前体频率,发现每10⁶个脾细胞中平均有300个(范围为4-1346个)对肽有反应的细胞。