Duke Cindy M P, Maguire Casey A, Keefer Michael C, Federoff Howard J, Bowers William J, Dewhurst Stephen
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Vaccine. 2007 Oct 16;25(42):7410-21. doi: 10.1016/j.vaccine.2007.08.015. Epub 2007 Aug 30.
HSV-1 amplicon vectors elicit strong T-cell responses to encoded antigens but the qualitative nature of these responses is poorly understood. Antigen-specific CD4(+) and CD8(+) T-cell responses to amplicon and adenovirus (rAd5) vectors encoding HIV-1 gp120 were assessed following immunization of mice, by performing intracellular cytokine staining for IFNgamma, IL2 and TNFalpha, following stimulation of splenocytes with a HIV-1 Env peptide pool. The quality of the primary T-cell response to amplicon and rAd5 vectors was strikingly similar, but there were qualitative differences in responses to amplicon vectors that incorporated different promoters upstream of gp120 - suggesting that promoters can significantly influence immune response quality. When prime-boost combinations were studied, a rAd5 prime and amplicon boost elicited the highest T-cell response. Furthermore, protocols that incorporated a rAd5 prime consistently elicited a greater proportion of polyfunctional CD4(+) T-cells-regardless of boost. This suggests that initial priming can shape immune response quality after a boost. Overall, these findings provide insight into effective vector combinations for HIV-1 vaccine development.
单纯疱疹病毒1型（HSV-1）扩增子载体可引发针对编码抗原的强烈T细胞反应，但这些反应的定性本质却知之甚少。在小鼠免疫后，通过在用HIV-1Env肽库刺激脾细胞后对IFNγ、IL2和TNFα进行细胞内细胞因子染色，评估了对编码HIV-1 gp120的扩增子和腺病毒（rAd5）载体的抗原特异性CD4(+)和CD8(+) T细胞反应。对扩增子和rAd5载体的初始T细胞反应质量惊人地相似，但对在gp120上游掺入不同启动子的扩增子载体的反应存在定性差异——这表明启动子可显著影响免疫反应质量。当研究初免-加强组合时，rAd5初免和扩增子加强引发了最高的T细胞反应。此外，无论加强方式如何，采用rAd5初免的方案始终能引发更大比例的多功能CD4(+) T细胞。这表明初始致敏可在加强后塑造免疫反应质量。总体而言，这些发现为HIV-1疫苗开发的有效载体组合提供了见解。
