Lodmell D L, Sumner J W, Esposito J J, Bellini W J, Ewalt L C
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840.
J Virol. 1991 Jun;65(6):3400-5. doi: 10.1128/JVI.65.6.3400-3405.1991.
Raccoon poxvirus (RCN) recombinants expressing the rabies virus internal structural nucleoprotein (RCN-N) protected A/WySnJ mice against a lethal challenge with street rabies virus (SRV). Maximum survival was achieved following vaccination by tail scratch and footpad (FP) SRV challenge. RCN-N-vaccinated mice inoculated in the FP with SRV were resistant to infection for at least 54 weeks postvaccination. Protection was also elicited by RCN recombinants expressing the rabies virus glycoprotein (RCN-G). Vaccination with RCN-G evoked rabies virus neutralizing antibody. Rabies virus neutralizing antibody was not detected in RCN-N-vaccinated mice prior to or following SRV infection. Radioimmunoprecipitation assays showed that sera from RCN-N-vaccinated mice which survived SRV infection did not contain antibody to SRV structural protein G, M, or NS. The mechanism(s) of N-induced resistance appears to correlate with the failure of peripherally inoculated SRV to enter the central nervous system (CNS). Support for this correlation with resistance was documented by the observations that SRV-inoculated RCN-N-vaccinated mice did not develop clinical signs of CNS rabies virus infection, infectious SRV was not detected in the spinal cord or brain following FP challenge, and all RCN-N-vaccinated mice died following direct intracranial infection of the CNS with SRV. These results suggest that factors other than anti-G neutralizing antibody are important in resistance to rabies virus and that the N protein should be considered for incorporation with the G protein in recombinant vaccines.
表达狂犬病病毒内部结构核蛋白（RCN-N）的浣熊痘病毒（RCN）重组体可保护A/WySnJ小鼠免受街狂犬病毒（SRV）的致死性攻击。通过尾部划痕接种疫苗并经足垫（FP）用SRV攻击后可实现最大存活率。用SRV接种足垫的RCN-N疫苗接种小鼠在接种疫苗后至少54周对感染具有抗性。表达狂犬病病毒糖蛋白（RCN-G）的RCN重组体也能引发保护作用。用RCN-G接种疫苗可诱生狂犬病病毒中和抗体。在SRV感染之前或之后，RCN-N疫苗接种小鼠中均未检测到狂犬病病毒中和抗体。放射免疫沉淀试验表明，在SRV感染中存活的RCN-N疫苗接种小鼠的血清中不含有针对SRV结构蛋白G、M或NS的抗体。N诱导抗性的机制似乎与外周接种的SRV无法进入中枢神经系统（CNS）有关。SRV接种的RCN-N疫苗接种小鼠未出现CNS狂犬病病毒感染的临床症状、在足垫攻击后脊髓或脑中未检测到传染性SRV以及所有RCN-N疫苗接种小鼠在CNS直接颅内感染SRV后均死亡等观察结果证明了这种与抗性的相关性。这些结果表明，除抗G中和抗体以外的因素在抗狂犬病病毒中也很重要，并且在重组疫苗中应考虑将N蛋白与G蛋白结合使用。
