Rasquinha Mahima T, Lasrado Ninaad, Sur Meghna, Mone Kiruthiga, Qiu Haowen, Riethoven Jean-Jack, Sobel Raymond A, Reddy Jay
School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Vaccines (Basel). 2022 Dec 29;11(1):76. doi: 10.3390/vaccines11010076.
Enteroviruses, which include Coxsackieviruses, are a common cause of virus infections in humans, and multiple serotypes of the group B Coxsackievirus (CVB) can induce similar diseases. No vaccines are currently available to prevent CVB infections because developing serotype-specific vaccines is not practical. Thus, developing a vaccine that induces protective immune responses for multiple serotypes is desired. In that direction, we created a live-attenuated CVB3 vaccine virus, designated mutant (Mt)10, that offers protection against myocarditis and pancreatitis induced by CVB3 and CVB4 in disease-susceptible A/J mice. Here, we report that the Mt10 vaccine protected against CVB4-triggered type 1 diabetes (T1D) in non-obese diabetic (NOD) mice but the expected subsequent development of spontaneous T1D in these genetically predisposed NOD mice was not altered. We noted that Mt10 vaccine induced significant amounts of neutralizing antibodies, predominantly of the IgG2c isotype, and the virus was not detected in vaccine-challenged animals. Furthermore, monitoring blood glucose levels-and to a lesser extent, insulin antibodies-was found to be helpful in predicting vaccine responses. Taken together, our data suggest that the monovalent Mt10 vaccine has the potential to prevent infections caused by multiple CVB serotypes, as we have demonstrated in various pre-clinical models.
肠道病毒，包括柯萨奇病毒，是人类病毒感染的常见病因，B组柯萨奇病毒（CVB）的多种血清型可引发相似疾病。目前尚无预防CVB感染的疫苗，因为研发血清型特异性疫苗并不实际。因此，人们期望开发一种能诱导针对多种血清型产生保护性免疫反应的疫苗。在这一方向上，我们构建了一种减毒活CVB3疫苗病毒，命名为突变体（Mt）10，它能在易感疾病的A/J小鼠中预防由CVB3和CVB4诱导的心肌炎和胰腺炎。在此，我们报告Mt10疫苗在非肥胖糖尿病（NOD）小鼠中可预防CVB4引发的1型糖尿病（T1D），但这些具有遗传易感性的NOD小鼠中预期随后出现的自发性T1D并未改变。我们注意到Mt10疫苗诱导产生了大量中和抗体，主要为IgG2c同种型，并且在接受疫苗攻击的动物中未检测到病毒。此外，监测血糖水平以及在较小程度上监测胰岛素抗体，被发现有助于预测疫苗反应。综上所述，我们的数据表明，正如我们在各种临床前模型中所证明的那样，单价Mt10疫苗有潜力预防由多种CVB血清型引起的感染。
