a Department of Experimental Therapeutics , Beckman Research Institute of City of Hope , Duarte , CA , USA.
b Department of Medical Specialties , City of Hope National Medical Center , Duarte , CA , USA.
Expert Rev Vaccines. 2018 Oct;17(10):889-911. doi: 10.1080/14760584.2018.1526085. Epub 2018 Oct 3.
It has been almost fifty years since the Towne strain was used by Plotkin and collaborators as the first vaccine candidate for cytomegalovirus (CMV). While that approach showed partial efficacy, there have been a multitude of challenges to improve on the promise of a CMV vaccine. Efforts have been dichotomized into a therapeutic vaccine for patients with CMV-infected allografts, either stem cells or solid organ, and a prophylactic vaccine for congenital infection.
This review will evaluate research prospects for a therapeutic vaccine for transplant recipients that recognizes CMV utilizing primarily T cell responses. Similarly, we will provide an extensive discussion on attempts to develop a vaccine to prevent the manifestations of congenital infection, based on eliciting a humoral anti-CMV protective response. The review will also describe newer developments that have upended the efforts toward such a vaccine through the discovery of a second pathway of CMV infection that utilizes an alternative receptor for entry using a series of antigens that have been determined to be important for prevention of infection.
There is a concerted effort to unify separate therapeutic and prophylactic vaccine strategies into a single delivery agent that would be effective for both transplant-related and congenital infection.
自 50 年前,普洛特金(Plotkin)及其合作者首次将托恩(Towne)株用于巨细胞病毒(CMV)疫苗候选株以来,已经过去了将近 50 年。虽然该方法显示出部分疗效,但在提高 CMV 疫苗的前景方面仍存在诸多挑战。人们努力将 CMV 疫苗分为两类:一种是用于治疗 CMV 感染的同种异体移植物(无论是干细胞还是实体器官)的患者的治疗性疫苗,另一种是用于预防先天性感染的预防性疫苗。
本综述将评估利用主要针对 T 细胞反应识别 CMV 的治疗性疫苗用于移植受者的研究前景。同样,我们将广泛讨论尝试开发一种疫苗以预防先天性感染的表现,该疫苗基于诱导体液抗 CMV 保护性反应。该综述还将描述通过发现第二种 CMV 感染途径来颠覆此类疫苗研发工作的最新进展,该途径利用替代进入受体,使用一系列已确定对预防感染很重要的抗原。
目前正在齐心协力将单独的治疗性和预防性疫苗策略统一到一个单一的递药载体中,以使其对移植相关和先天性感染都有效。