一种设计用于全球使用的合成共有序列打乱抗原HIV-1疫苗的研发。

Development of a synthetic consensus sequence scrambled antigen HIV-1 vaccine designed for global use.

作者信息

Thomson Scott A, Jaramillo Angel B, Shoobridge Maryanne, Dunstan Kerrie J, Everett Beth, Ranasinghe Charani, Kent Stephen J, Gao Ke, Medveckzy Jill, Ffrench Rosemary A, Ramshaw Ian A

机构信息

Division of Immunology and Genetics, John Curtin School of Medical Research (JCSMR), Australian National University, P.O. Box 334, Canberra, ACT 2601, Australia.

出版信息

Vaccine. 2005 Sep 7;23(38):4647-57. doi: 10.1016/j.vaccine.2005.04.045.

DOI:10.1016/j.vaccine.2005.04.045

PMID:15964105

Abstract

Induction of high levels of broadly reactive cytotoxic T lymphocytes (CTL) remains a promising approach for an effective HIV-1 vaccine. We have developed a novel genetic-based vaccine strategy that encodes consensus overlapping peptide sets from all HIV-1 proteins scrambled together. This synthetic scrambled antigen vaccine (SAVINE) strategy has significant advantages, e.g. capacity to encode more antigens safely and is very flexible compared to traditional isolate-based strategies. The SAVINE vaccine strategy is clearly immunogenic, being able to restimulate a range of human HIV-1 specific responses in vitro and induce HIV-1 specific immunity in vivo in mice. Interestingly, different in vivo delivery strategies affected the resulting immunity and immunodominance pattern in mice. This platform strategy could be used for other infections and cancers where T cell responses are important for protection.

摘要

诱导高水平的广泛反应性细胞毒性T淋巴细胞（CTL）仍然是开发有效HIV-1疫苗的一种有前景的方法。我们已经开发出一种基于基因的新型疫苗策略，该策略编码来自所有HIV-1蛋白的共有重叠肽集，并将它们混合在一起。这种合成的混合抗原疫苗（SAVINE）策略具有显著优势，例如能够安全地编码更多抗原，并且与传统的基于病毒分离株的策略相比非常灵活。SAVINE疫苗策略具有明显的免疫原性，能够在体外重新刺激一系列人类HIV-1特异性反应，并在小鼠体内诱导HIV-1特异性免疫。有趣的是，不同的体内递送策略会影响小鼠产生的免疫和免疫优势模式。这种平台策略可用于T细胞反应对保护作用很重要的其他感染和癌症。