Rooney J F, Wohlenberg C, Cremer K J, Moss B, Notkins A L
Laboratory of Oral Medicine, National Institute of Dental Research, Bethesda, Maryland 20892.
J Virol. 1988 May;62(5):1530-4. doi: 10.1128/JVI.62.5.1530-1534.1988.
Previously we showed that mice immunized with a vaccinia virus vector expressing the herpes simplex virus type 1 (HSV-1) glycoprotein D (gD) gene (vaccinia/gD) were protected against both lethal and latent infections with HSV-1 for at least 6 weeks after immunization (K. J. Cremer, M. Mackett, C. Wohlenberg, A. L. Notkins, and B. Moss, Science 228:737-740, 1985). In the experiments described here, we examined long-term immunity to HSV following vaccinia/gD vaccination, the effect of revaccination with vaccinia/gD, and the impact of previous immunity to vaccinia virus on immunization with the gD recombinant. Mice immunized with vaccinia/gD showed 100, 100, and 80% protection against lethal infection with HSV-1 at 18, 44, and 60 weeks postimmunization, respectively. Protection against latent trigeminal ganglionic infection was 70, 50, and 31% at 6, 41, and 60 weeks postvaccination, respectively. To study the effect of reimmunization on antibody levels, mice vaccinated with vaccinia/gD were given a second immunization (booster dose) 3 months after the first. These mice developed a 10-fold increase in neutralizing-antibody titer (221 to 2,934) and demonstrated a significant increase in protection against lethal HSV-1 challenge compared with animals that received only one dose of vaccinia/gD. To determine whether preexisting immunity to vaccinia virus inhibited the response to vaccination with vaccinia/gD virus, mice were immunized with a recombinant vaccinia virus vector expressing antigens from either influenza A or hepatitis B virus and were then immunized (2 to 3 months later) with vaccinia/gD. These mice showed reduced titers of neutralizing antibody to HSV-1 and decreased protection against both lethal and latent infections with HSV-1 compared with animals vaccinated only with vaccinia/gD. We conclude that vaccination with vaccinia/gD produces immunity against HSV-1 that lasts over 1 year and that this immunity can be increased by a booster but that prior immunization with a vaccinia recombinant virus expressing a non-HSV gene reduces the levels of neutralizing antibody and protective immunity against HSV-1 challenge.
此前我们发现，用表达单纯疱疹病毒1型（HSV-1）糖蛋白D（gD）基因的痘苗病毒载体（痘苗/gD）免疫的小鼠，在免疫后至少6周内可抵御HSV-1的致死性感染和潜伏感染（K. J. 克雷默、M. 麦基特、C. 沃伦贝格、A. L. 诺特金斯和B. 莫斯，《科学》228:737 - 740，1985年）。在本文所述实验中，我们检测了痘苗/gD疫苗接种后对HSV的长期免疫力、再次接种痘苗/gD的效果以及既往对痘苗病毒的免疫力对gD重组疫苗接种的影响。用痘苗/gD免疫的小鼠在免疫后18、44和60周时，对HSV-1致死性感染的保护率分别为100%、100%和80%。接种疫苗后6、41和60周时，对潜伏性三叉神经节感染的保护率分别为70%、50%和31%。为研究再次免疫对抗体水平的影响，用痘苗/gD接种的小鼠在首次接种3个月后进行第二次免疫（加强剂量）。与仅接受一剂痘苗/gD的动物相比，这些小鼠的中和抗体滴度增加了10倍（从221增至2934），并且在抵御HSV-1致死性攻击方面的保护作用显著增强。为确定既往对痘苗病毒的免疫力是否会抑制对痘苗/gD病毒接种的反应，用表达甲型流感病毒或乙型肝炎病毒抗原的重组痘苗病毒载体免疫小鼠，然后（2至3个月后）用痘苗/gD免疫。与仅接种痘苗/gD的动物相比，这些小鼠对HSV-1的中和抗体滴度降低，对HSV-1致死性感染和潜伏感染的保护作用减弱。我们得出结论，接种痘苗/gD可产生针对HSV-1的免疫力，且这种免疫力可持续1年以上，加强免疫可增强这种免疫力，但既往用表达非HSV基因的痘苗重组病毒免疫会降低中和抗体水平以及针对HSV-1攻击的保护性免疫力。
