The 17D-204 Vaccine Strain-Induced Protection against Virulent Yellow Fever Virus Is Mediated by Humoral Immunity and CD4+ but not CD8+ T Cells.
The 17D-204 Vaccine Strain-Induced Protection against Virulent Yellow Fever Virus Is Mediated by Humoral Immunity and CD4+ but not CD8+ T Cells.
复制标题
DOI：
10.1371/journal.ppat.1005786
复制
发表时间：
2016-07
期刊：
影响因子：
6.7
通讯作者：
Ryman KD
中科院分区：
文献类型：
--
作者：
Watson AM;Lam LK;Klimstra WB;Ryman KD
A gold standard of antiviral vaccination has been the safe and effective live-attenuated 17D-based yellow fever virus (YFV) vaccines. Among more than 500 million vaccinees, only a handful of cases have been reported in which vaccinees developed a virulent wild type YFV infection. This efficacy is presumed to be the result of both neutralizing antibodies and a robust T cell response. However, the particular immune components required for protection against YFV have never been evaluated. An understanding of the immune mechanisms that underlie 17D-based vaccine efficacy is critical to the development of next-generation vaccines against flaviviruses and other pathogens. Here we have addressed this question for the first time using a murine model of disease. Similar to humans, vaccination elicited long-term protection against challenge, characterized by high neutralizing antibody titers and a robust T cell response that formed long-lived memory. Both CD4+ and CD8+ T cells were polyfunctional and cytolytic. Adoptive transfer of immune sera or CD4+ T cells provided partial protection against YFV, but complete protection was achieved by transfer of both immune sera and CD4+ T cells. Thus, robust CD4+ T cell activity may be a critical contributor to protective immunity elicited by highly effective live attenuated vaccines. The 17D line yellow fever virus (YFV) vaccines are some of the safest and most effective live-attenuated virus vaccines ever produced, protecting recipients for life against deadly yellow fever (YF). As a testament to this safety and efficacy, the 17D line of live-attenuated vaccines has become an important model for the design of future vaccines. However, we still lack a fundamental understanding of the protective immunity elicited against the virulent YFV, a knowledge gap that must be overcome to inform the design of future live-attenuated and subunit vaccines. Humans develop robust antibody and T cell responses following vaccination, leading some to suggest that vaccine-elicited CD8+ T cells are important for protection against virulent YFV. Since this can never be tested in humans, we have used mice to model immunity to the 17D-204 vaccine strain. We found that CD4+ T cells elicited by 17D-204 contributed to protection against virulent YFV, but CD8+ T cells had no effect on the outcomes of survival or disease. Our study is the first to demonstrate that vaccine-elicited CD4+ T cells can protect against YFV infection. These results suggest that vaccine developers should consider the importance of CD4+ T cells when designing vaccines against viruses similar to YFV.
