狂犬病病毒HEP-Flury M基因重排在小鼠致病性和保护性研究

目的 了解M基因重排对病毒致病性和免疫保护性的影响,从而为狂犬病疫苗的开发提供更适合的候选株。方法 将病毒rHEP-Flury和M基因重排株颅内接种1～3 d龄的乳鼠,测定病毒在乳鼠上的半数致死量(LD₅₀)。将rHEP-Flury和M基因重排株以10³、10⁴和10⁵ FFU免疫接种6~8周龄的成鼠,然后用标准攻毒株CVS-24进行颅内感染小鼠,测定小鼠的存活率。同时用ELISA方法检测小鼠血清抗体水平。结果 狂犬病病毒HEP-Flury的M基因重排后,病毒对乳鼠的毒力随着M基因位置远离病毒启动子位置增强,即M24和10⁵FFU时,M基因重排对病毒在成鼠上的保护性没有统计学意义影响;当接种剂量为10³FFU时,M基因重排病毒对小鼠的保护性明显高于rHEP-Flury。结论 狂犬病病毒HEP-Flury的M基因重排能够降低病毒对乳鼠的毒力,提高对小鼠的保护性,为狂犬病疫苗开发奠定基础。

Pathogenicity and protection in mice of rearranging the M gene of RABV HEP-Flury

In order to help rabies vaccine candidate construction,the lethality and immunological protection between rHEP-Flury and M gene rearranged viruses were compared and analyzed.Lethality in suckling mice was performed by intracranial inoculating rHEP-Flury or M gene rearranged viruses,then LD 50 was calculated.Protection of mice was performed by immunized once intramuscularly with different doses of rHEP-Flury or M gene rearranged viruses,then mice were challenged IC with CVS-24 and survivor numbers were evaluated.At the same time,the antibody level was assessed by ELISA.The lethality in suckling mice increased as the M gene was moved successively away from promoter proximal position to successive positions down the viral genome,that is M2