Tibbetts Scott A, McClellan J Scott, Gangappa Shivaprakash, Speck Samuel H, Virgin Herbert W
Department of Pathology & Immunology and Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
J Virol. 2003 Feb;77(4):2522-9. doi: 10.1128/jvi.77.4.2522-2529.2003.
The fundamental question of whether a primed immune system is capable of preventing latent gammaherpesvirus infection remains unanswered. Recent studies showing that vaccination can reduce acute replication and short-term latency but cannot alter long-term latency further call into question the possibility of achieving sterilizing immunity against gammaherpesviruses. Using the murine gammaherpesvirus 68 (gammaHV68) system, we demonstrate that it is possible to effectively vaccinate against long-term latency. By immunizing mice with a gammaHV68 mutant virus that is deficient in its ability to reactivate from latency, we reduced latent infection of wild-type challenge virus to a level below the limit of detection. Establishment of latency was inhibited by vaccination regardless of whether mice were challenged intraperitoneally or intranasally. Passive transfer of antibody from vaccinated mice could partially reconstitute the effect, demonstrating that antibody is an important component of vaccination. These results demonstrate the potential of a memory immune response against gammaherpesviruses to alter long-term latency and suggest that limiting long-term latent infection in a clinically relevant situation is an attainable goal.
已致敏的免疫系统是否能够预防潜伏性γ疱疹病毒感染这一基本问题仍未得到解答。最近的研究表明，疫苗接种可以减少急性复制和短期潜伏，但无法进一步改变长期潜伏，这进一步质疑了实现针对γ疱疹病毒的无菌免疫的可能性。利用小鼠γ疱疹病毒68（γHV68）系统，我们证明了有效接种疫苗以对抗长期潜伏是可能的。通过用一种从潜伏状态重新激活能力缺陷的γHV68突变病毒免疫小鼠，我们将野生型攻击病毒的潜伏感染降低到检测限以下水平。无论小鼠是经腹腔还是经鼻攻击，疫苗接种均能抑制潜伏状态的建立。来自接种疫苗小鼠的抗体的被动转移可部分重建这种效果，表明抗体是疫苗接种的重要组成部分。这些结果证明了针对γ疱疹病毒的记忆性免疫反应改变长期潜伏的潜力，并表明在临床相关情况下限制长期潜伏感染是一个可实现的目标。
