Choi K Yeon, McGregor Alistair
Health Science Center, Department of Microbial Pathogenesis & Immunology, College of Medicine, Texas A&M University, Bryan, TX 77807-3260, USA.
Viruses. 2021 Jul 27;13(8):1467. doi: 10.3390/v13081467.
A vaccine against congenital cytomegalovirus infection is a high priority. Guinea pig cytomegalovirus (GPCMV) is the only congenital CMV small animal model. GPCMV encodes essential glycoprotein complexes for virus entry (gB, gH/gL/gO, gM/gN) including a pentamer complex (gH/gL/GP129/GP131/GP133 or PC) for endocytic cell entry. The cohorts for protection against congenital CMV are poorly defined. Neutralizing antibodies to the viral glycoprotein complexes are potentially more important than an immunodominant T-cell response to the pp65 protein. In GPCMV, GP83 (pp65 homolog) is an evasion factor, and the GP83 mutant GPCMV has increased sensitivity to type I interferon. Although GP83 induces a cell-mediated response, a GP83-only-based vaccine strategy has limited efficacy. GPCMV attenuation via GP83 null deletion mutant in glycoprotein PC positive or negative virus was evaluated as live-attenuated vaccine strains (GP83dPC+/PC-). Vaccinated animals induced antibodies to viral glycoprotein complexes, and PC+ vaccinated animals had sterilizing immunity against wtGPCMV challenge. In a pre-conception vaccine (GP83dPC+) study, dams challenged mid-2nd trimester with wtGPCMV had complete protection against congenital CMV infection without detectable virus in pups. An unvaccinated control group had 80% pup transmission rate. Overall, gB and PC antibodies are key for protection against congenital CMV infection, but a response to pp65 is not strictly necessary.
研发针对先天性巨细胞病毒感染的疫苗是当务之急。豚鼠巨细胞病毒（GPCMV）是唯一的先天性巨细胞病毒小动物模型。GPCMV编码病毒进入所必需的糖蛋白复合物（gB、gH/gL/gO、gM/gN），包括用于内吞细胞进入的五聚体复合物（gH/gL/GP129/GP131/GP133或PC）。针对先天性巨细胞病毒感染的保护性队列定义不明确。针对病毒糖蛋白复合物的中和抗体可能比针对pp65蛋白的免疫显性T细胞反应更重要。在GPCMV中，GP83（pp65同源物）是一种逃逸因子，GP83突变的GPCMV对I型干扰素的敏感性增加。尽管GP83诱导细胞介导的反应，但仅基于GP83的疫苗策略疗效有限。通过糖蛋白PC阳性或阴性病毒中的GP83缺失突变体对GPCMV进行减毒，评估其作为减毒活疫苗株（GP83dPC+/PC-）。接种疫苗的动物诱导产生针对病毒糖蛋白复合物的抗体，接种PC+疫苗的动物对野生型GPCMV攻击具有无菌免疫力。在一项孕前疫苗（GP83dPC+）研究中，在妊娠中期用野生型GPCMV攻击的母鼠对先天性巨细胞病毒感染具有完全保护作用，幼崽中未检测到病毒。未接种疫苗的对照组幼崽传播率为80%。总体而言，gB和PC抗体是预防先天性巨细胞病毒感染的关键，但对pp65的反应并非严格必需。
