Liu Yujun, Gong Hao, Zhu Jiaming, Liu Fenyong
School of Public Health, University of California, Berkeley, CA 94720, USA.
Program in Comparative Biochemistry, University of California, Berkeley, CA 94720, USA.
Pathogens. 2025 Mar 25;14(4):314. doi: 10.3390/pathogens14040314.
Attenuated strains are promising oral vectors for vaccination against human infectious diseases. Human cytomegalovirus (CMV) is among the most common causes of disability in children, including intellectual disability and sensorineural hearing loss. Developing an anti-CMV vaccine is a major public health priority. We report in this study the construction of a new attenuated strain to express murine cytomegalovirus (MCMV) M25 protein and its use for vaccination in mice against MCMV infection. In mice orally vaccinated with the constructed vector carrying the M25 expression cassette, we revealed a substantial induction of anti-MCMV serum IgG and mucosal IgA humoral responses and a considerable elicitation of anti-MCMV T cell responses. When the vaccinated mice were challenged intraperitoneally and intranasally with MCMV, we observed a significant inhibition of virus infection and growth in various organs including spleens, livers, lungs, and salivary glands, compared to the non-vaccinated animals or those receiving a control vaccine without M25 protein expression. Moreover, we showed effective protection of these vaccinated mice from MCMV challenge. Our study provides the first direct evidence that an attenuated -based vector with the MCMV M25 expression cassette can induce strong humoral and T cell responses and provide effective protection against MCMV infection. These results illustrate the feasibility of engineering -based vectors expressing the M25 antigen for anti-CMV oral vaccine development.
减毒株是用于预防人类传染病疫苗接种的有前景的口服载体。人类巨细胞病毒（CMV）是儿童残疾的最常见原因之一，包括智力残疾和感音神经性听力损失。开发抗CMV疫苗是一项重大的公共卫生优先事项。我们在本研究中报告了一种表达鼠巨细胞病毒（MCMV）M25蛋白的新型减毒株的构建及其在小鼠中用于预防MCMV感染疫苗接种的应用。在用携带M25表达盒的构建载体口服接种的小鼠中，我们发现诱导了大量的抗MCMV血清IgG和粘膜IgA体液反应以及相当程度的抗MCMV T细胞反应。当对接种疫苗的小鼠进行腹腔内和鼻内MCMV攻击时，与未接种疫苗的动物或接受无M25蛋白表达的对照疫苗的动物相比，我们观察到在包括脾脏、肝脏、肺和唾液腺在内的各种器官中病毒感染和生长受到显著抑制。此外，我们表明这些接种疫苗的小鼠对MCMV攻击具有有效的保护作用。我们的研究提供了首个直接证据，即带有MCMV M25表达盒的减毒载体可诱导强烈的体液和T细胞反应，并提供针对MCMV感染的有效保护。这些结果说明了构建表达M25抗原的减毒载体用于抗CMV口服疫苗开发的可行性。
