Messer Ronald J, Dittmer Ulf, Peterson Karin E, Hasenkrug Kim J
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12260-5. doi: 10.1073/pnas.0404769101. Epub 2004 Aug 5.
The current experiments use the Friend retrovirus model to demonstrate that vaccine-primed B cells are essential for sterilizing immunity, and the results indicate that the requisite function of these cells is the production of virus-neutralizing antibodies rather than priming or reactivation of T cells. B cell-deficient mice were poorly protected by vaccination, but adoptive transfer experiments showed that the T cells from B cell-deficient mice were primed as well as those from wild-type mice. Furthermore, passive transfer of virus-neutralizing antibodies completely compensated for B cell deficiency. The presence of virus-neutralizing antibodies at the time of infection was crucial for vaccine efficacy. Interestingly, virus-neutralizing antibodies worked synergistically with vaccine-primed T cells to provide a level of protection many orders of magnitude greater than either antibodies or immune T cells alone. Nonneutralizing antibodies also contributed to protection and acted cooperatively with neutralizing antibodies to reduce infection levels. These results emphasize the importance of inducing both T cell responses and virus-neutralizing antibody responses for effective retroviral vaccine protection.
当前的实验使用弗瑞德氏逆转录病毒模型来证明经疫苗致敏的B细胞对于无菌免疫至关重要,结果表明这些细胞的必要功能是产生病毒中和抗体,而非启动或激活T细胞。B细胞缺陷型小鼠通过接种疫苗得到的保护较差,但过继转移实验表明,B细胞缺陷型小鼠的T细胞与野生型小鼠的T细胞一样被启动。此外,病毒中和抗体的被动转移完全弥补了B细胞缺陷。感染时存在病毒中和抗体对于疫苗效力至关重要。有趣的是,病毒中和抗体与经疫苗致敏的T细胞协同作用,提供的保护水平比单独的抗体或免疫T细胞高出许多个数量级。非中和抗体也有助于保护,并与中和抗体协同作用以降低感染水平。这些结果强调了诱导T细胞应答和病毒中和抗体应答对于有效的逆转录病毒疫苗保护的重要性。