Amara Rama Rao, Nigam Pragati, Sharma Sunita, Liu Jinyan, Bostik Vanda
Emory Vaccine Center and Yerkes National Primate Research Center and Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, Georgia 30329, USA.
J Virol. 2004 Apr;78(8):3811-6. doi: 10.1128/jvi.78.8.3811-3816.2004.
The currently used smallpox vaccine is associated with a high incidence of adverse events, and there is a serious need for a safe and effective alternative vaccine. Here, we carried out a longitudinal evaluation of vaccinia virus-specific CD4 and CD8 T cells in smallpox-vaccinated individuals by using a highly sensitive intracellular cytokine staining assay. Our results demonstrate that, in addition to the CD8 response, the smallpox vaccinations raised a robust CD4 response with a Th1-dominant cytokine profile. These CD4 T cells were stable and exhibited only a twofold contraction between peak effector and memory phases compared with an approximate sevenfold contraction for CD8 cells. A significant proportion of vaccinated individuals lost detectable CD8 memory while maintaining CD4 memory. After a booster immunization, these individuals generated a robust CD8 response, which some of them rapidly lost. Thus, the current smallpox vaccine provides long-lasting CD4 help that may be critical for long-lived B-cell memory. We suggest that the provision of adequate CD4 help for CD8 and humoral effector functions will be critical to the success of the next generation of smallpox vaccines.
目前使用的天花疫苗与高不良事件发生率相关，因此迫切需要一种安全有效的替代疫苗。在此，我们通过使用高度敏感的细胞内细胞因子染色测定法，对天花疫苗接种个体中的痘苗病毒特异性CD4和CD8 T细胞进行了纵向评估。我们的结果表明，除了CD8反应外，天花疫苗接种还引发了具有Th1主导细胞因子谱的强大CD4反应。这些CD4 T细胞稳定，与CD8细胞约七倍的收缩相比，在效应峰值和记忆阶段之间仅表现出两倍的收缩。相当一部分接种疫苗的个体在维持CD4记忆的同时失去了可检测到的CD8记忆。在加强免疫后，这些个体产生了强大的CD8反应，但其中一些反应很快消失。因此，当前的天花疫苗提供了持久的CD4辅助，这可能对长寿B细胞记忆至关重要。我们认为，为CD8和体液效应功能提供足够的CD4辅助对于下一代天花疫苗的成功至关重要。
