Schleiss Mark R, Stroup Greg, Pogorzelski Kelly, McGregor Alistair
Division of Infectious Diseases, University of Minnesota Medical School, Department of Pediatrics, Center for Infectious Diseases and Microbiology Translational Research, Minneapolis, MN 55455, United States.
Vaccine. 2006 Sep 11;24(37-39):6175-86. doi: 10.1016/j.vaccine.2006.06.077. Epub 2006 Jul 18.
It is unclear if protective immunity can be conferred by a cytomegalovirus (CMV) vaccine encoding a single protein subunit, or if multiple viral genes need to be targeted. Using the guinea pig model of congenital CMV infection, these studies examined the immunogenicity and efficacy of a DNA vaccine based on the guinea pig cytomegalovirus (GPCMV) genome cloned as a non-infectious BAC plasmid, modified by transposon insertion into the homolog of the HCMV tegument protein, UL48. Following vaccination of female Hartley guinea pigs with BAC DNA, adverse GPCMV-related pregnancy outcome were assessed after establishment of pregnancy, followed by GPCMV third-trimester challenge. Animals immunized with recombinant BACmid engendered anti-GPCMV antibodies by ELISA assay. Immunogenicity of BAC plasmid DNA was augmented by inclusion of the lipid adjuvant, DOTMA/DOPE, in the vaccine regimen. Among pups born to 12 control (sham-immunized) dams challenged with GPCMV in the third trimester, mortality was 23/35 (66%). In contrast, among evaluable pregnancy outcomes in pups born to 10 BAC-immunized pregnant dams, preconception immunization resulted in reduced pup mortality, to 10/34 pups (29%; p<0.005 versus control, Fisher's exact test). In addition, vaccinated dams had reduced viral load, compared to controls, as assessed by quantitative, real-time PCR.
目前尚不清楚编码单个蛋白质亚基的巨细胞病毒（CMV）疫苗是否能赋予保护性免疫，或者是否需要靶向多个病毒基因。利用先天性CMV感染的豚鼠模型，这些研究检测了一种基于豚鼠巨细胞病毒（GPCMV）基因组克隆为非感染性BAC质粒的DNA疫苗的免疫原性和效力，该质粒通过转座子插入人巨细胞病毒（HCMV）被膜蛋白UL48的同源物进行修饰。在用BAC DNA对雌性Hartley豚鼠进行疫苗接种后，在怀孕确立后评估与GPCMV相关的不良妊娠结局，随后进行GPCMV孕晚期攻击。通过ELISA检测，用重组BACmid免疫的动物产生了抗GPCMV抗体。在疫苗方案中加入脂质佐剂DOTMA/DOPE可增强BAC质粒DNA的免疫原性。在12只孕晚期接受GPCMV攻击的对照（假免疫）母鼠所生的幼崽中，死亡率为23/35（66%）。相比之下，在10只接受BAC免疫的怀孕母鼠所生幼崽的可评估妊娠结局中，孕前免疫导致幼崽死亡率降低，为10/34只幼崽（29%；与对照组相比，Fisher精确检验p<0.005）。此外，通过定量实时PCR评估，与对照组相比，接种疫苗的母鼠病毒载量降低。
