预存免疫对基于仙台病毒载体开发的疫苗免疫效果的影响

Influence of pre-existing immunity on the immunogenicity of Sendai virus vector-based vaccines

目的研究仙台病毒(Sendai virus,SeV)预存免疫对基于仙台病毒载体开发的Ⅱ型单纯疱疹病毒(herpes simplex virus 2,HSV-2)疫苗SeV-dF/HSV-2 ICP27和SeV-dF/HSV-2 gD免疫效果的影响,为克服预存免疫的影响提供数据参考。方法使用不同剂量(3lg、4lg、5lg、6lg、7lg、8lg CIU)仙台病毒免疫小鼠,建立不同程度预存免疫模型。对建立了预存免疫的小鼠分别免疫SeV-dF/HSV-2 ICP27和SeV-dF/HSV-2 gD,采用酶联免疫斑点检测(ELISPOT)法测定小鼠脾淋巴细胞分泌的ICP27特异性IFN-γ活性,蚀斑减少中和试验(PRNT50)测定小鼠血清中HSV-2中和抗体效价。结果小鼠经不同剂量仙台病毒免疫后建立了预存免疫,且仙台病毒中和抗体效价随着免疫剂量的增加而升高,呈现剂量依赖效应。3lg^8lg CIU仙台病毒免疫小鼠所建立的预存免疫均可对SeV-dF/HSV-2 ICP27诱导的细胞免疫产生显著抑制作用,但对SeV-dF/HSV-2 gD诱导的体液免疫未产生显著抑制作用。结论预存免疫对基于仙台病毒载体开发的疫苗的影响需要考虑预存病毒中和抗体是否存在,同时病毒载体表达何种外源蛋白也是需要考虑的因素之一。

Objective To investigate the influence of pre-existing immunity on the immunogenicity of Sendai virus vector-based herpes simplex virus type 2(HSV-2)vaccines(SeV-dF/HSV-2 ICP27 and SeV-dF/HSV-2 gD)in order to provide reference for further research on reducing the influence of pre-existing immunity.Methods Varying degrees of pre-existing immunity were induced in mice by immunizing with Sendai virus at 3lg,4lg,5lg,6lg,7lg and 8lg cell infectious units(CIU).ELISPOT assay was used to evaluate the secretion of ICP27-specific INF-γby splenic lymphocytes following immunization the mice with SeV-dF/HSV-2 ICP27.HSV-2 neutralizing antibody titers were measured by plaque reduction neutralization test(PRNT)after immunization with SeV-dF/HSV-2 gD.Results Pre-existing immunity was successfully induced in mice using different doses of Sendai virus.The titer of neutralizing antibody against Sendai virus was raised with the increasing immunization dose,showing a dose-dependent effect.The pre-existing immunity induced in mice with 3lg-8lg CIU of Sendai virus showed significant inhibitory effects on cellular immunity induced by SeV-dF/HSV-2 ICP27,but no significant inhibition on humoral immunity induced by SeV-dF/HSV-2 gD.Conclusions The existence of neutralizing antibody to Sendai virus vector and the kind of protein expressed by the vector should be taken into consideration in terms of the impact of pre-existing immunity on the immunogenicity of Sendai virus vector-based vaccines.