Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10065-6399, USA.
Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4281-6. doi: 10.1073/pnas.1000621107. Epub 2010 Feb 16.
To improve the efficacy of T cell-based vaccination, we pursued the principle that CD4(+) T cells provide help for functional CD8(+) T cell immunity. To do so, we administered HIV gag to mice successively as protein and DNA vaccines. To achieve strong CD4(+) T cell immunity, the protein vaccine was targeted selectively to DEC-205, a receptor for antigen presentation on dendritic cells. This targeting helped CD8(+) T cell immunity develop to a subsequent DNA vaccine and improved protection to intranasal challenge with recombinant vaccinia gag virus, including more rapid accumulation of CD8(+) T cells in the lung. The helper effect of dendritic cell-targeted protein vaccine was mimicked by immunization with specific MHC II binding HIV gag peptides but not peptides from a disparate Yersinia pestis microbe. CD4(+) helper cells upon adoptive transfer allowed wild-type, but not CD40(-/-), recipient mice to respond better to the DNA vaccine. The transfer also enabled recipients to more rapidly accumulate gag-specific CD8(+) T cells in the lung following challenge with vaccinia gag virus. Thus, complementary prime boost vaccination, in which prime and boost favor distinct types of T cell immunity, improves plasmid DNA immunization, including mobilization of CD8(+) T cells to sites of infection.
为了提高基于 T 细胞的疫苗接种的疗效，我们遵循这样一个原则，即 CD4(+)T 细胞为功能性 CD8(+)T 细胞免疫提供帮助。为此，我们先后用 HIV gag 蛋白和 DNA 疫苗对小鼠进行了给药。为了实现强大的 CD4(+)T 细胞免疫，将蛋白疫苗选择性靶向 DEC-205，这是树突状细胞上抗原呈递的受体。这种靶向作用有助于 CD8(+)T 细胞免疫发展到随后的 DNA 疫苗，并改善对重组痘苗病毒 gag 的鼻腔内挑战的保护作用，包括 CD8(+)T 细胞更快地在肺部积聚。用特异性 MHC II 结合的 HIV gag 肽而非来自不同的鼠疫耶尔森菌的肽免疫可模拟树突状细胞靶向蛋白疫苗的辅助作用。过继转移的 CD4(+)辅助细胞使野生型，但不是 CD40(-/-)，的受体小鼠对 DNA 疫苗的反应更好。转移还使受体在接种痘苗病毒 gag 后更快地在肺部积累 gag 特异性 CD8(+)T 细胞。因此，互补的初级加强疫苗接种，其中初级和加强疫苗优先考虑不同类型的 T 细胞免疫，可提高质粒 DNA 免疫，包括将 CD8(+)T 细胞动员到感染部位。
