Rouvio Ory, Dvorkin Tatyana, Amir-Kroll Hila, Atias Danit, Cohen Irun R, Rager-Zisman Bracha, Porgador Angel
Department of Microbiology and Immunology, Faculty of Health Sciences and the Cancer Research Center, Ben Gurion University of the Negev, Beer Sheva 84105, Israel.
Vaccine. 2005 May 20;23(27):3508-18. doi: 10.1016/j.vaccine.2005.02.002.
Murine cytomegalovirus (MCMV) infection is associated with persistence of virus in the salivary glands, despite relatively rapid clearance of virus from the spleen. An effective immunization against MCMV should prevent such viral persistence. We previously reported that a peptide (p458) from the sequence of the 60 kDa heat shock protein (HSP60) molecule in a conjugate vaccine can provide T cell help for the induction of protecting antibody against bacterial capsular polysaccharides. We now report that the p458 peptide as a carrier peptide can also enhance the immunogenicity of a dominant CTL epitope of the MCMV pp89 antigen-89pep. We synthesized a linear combined peptide: chimeric p458-89pep. We immunized young BALB/c mice and challenged them with MCMV. We found that the p458-89pep chimeric peptide was more effective than the 89pep in inducing 89pep-specific IFN(gamma) secretion and specific CTL activity. Moreover, the p458-89pep chimeric peptide induced sustained IFN(gamma) secretion in the salivary gland specific to 89pep and only this immunization was associated with clearance of virus from the salivary gland. These results suggest that a peptide epitope of HSP60 may be advantageous as a T cell carrier peptide in the induction of specific T cell immunity against infectious agents.
鼠巨细胞病毒（MCMV）感染与病毒在唾液腺中的持续存在有关，尽管病毒能较快地从脾脏中清除。针对MCMV的有效免疫应能防止这种病毒的持续存在。我们之前报道过，在结合疫苗中，来自60 kDa热休克蛋白（HSP60）分子序列的一种肽（p458）可以为诱导针对细菌荚膜多糖的保护性抗体提供T细胞辅助。我们现在报道，p458肽作为载体肽还能增强MCMV pp89抗原的显性CTL表位（89pep）的免疫原性。我们合成了一种线性组合肽：嵌合p458-89pep。我们用其免疫年轻的BALB/c小鼠，然后用MCMV对它们进行攻击。我们发现，p458-89pep嵌合肽在诱导89pep特异性IFN（γ）分泌和特异性CTL活性方面比89pep更有效。此外，p458-89pep嵌合肽在唾液腺中诱导了针对89pep的持续IFN（γ）分泌，只有这种免疫与唾液腺中病毒的清除有关。这些结果表明，HSP60的肽表位作为T细胞载体肽，在诱导针对感染因子的特异性T细胞免疫方面可能具有优势。
