Galen James E, Wahid Rezwanul, Buskirk Amanda D
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Center for Drug Evaluation and Research, Office of Pharmaceutical Quality, Office of Process and Facilities, Division of Microbiology Assessment II, U.S. Food and Drug Administration, Silver Spring, MD 20903, USA.
Vaccines (Basel). 2021 Feb 17;9(2):162. doi: 10.3390/vaccines9020162.
The use of live-attenuated bacterial vaccines as carriers for the mucosal delivery of foreign antigens to stimulate the mucosal immune system was first proposed over three decades ago. This novel strategy aimed to induce immunity against at least two distinct pathogens using a single bivalent carrier vaccine. It was first tested using a live-attenuated serovar Typhi strain in clinical trials in 1984, with excellent humoral immune responses against the carrier strain but only modest responses elicited against the foreign antigen. Since then, clinical trials with additional -based carrier vaccines have been conducted. As with the original trial, only modest foreign antigen-specific immunity was achieved in most cases, despite the incorporation of incremental improvements in antigen expression technologies and carrier design over the years. In this review, we will attempt to deconstruct carrier vaccine immunogenicity in humans by examining the basis of bacterial immunity in the human gastrointestinal tract and how the gut detects and responds to pathogens versus benign commensal organisms. Carrier vaccine design will then be explored to determine the feasibility of retaining as many characteristics of a pathogen as possible to elicit robust carrier and foreign antigen-specific immunity, while avoiding over-stimulation of unacceptably reactogenic inflammatory responses.
三十多年前首次提出使用减毒活细菌疫苗作为载体进行黏膜递送外来抗原，以刺激黏膜免疫系统。这一新颖策略旨在利用单一二价载体疫苗诱导针对至少两种不同病原体的免疫。1984年首次在临床试验中使用减毒伤寒血清型菌株进行测试，对载体菌株产生了良好的体液免疫反应，但对外来抗原引发的反应较小。从那时起，已开展了使用其他载体疫苗的临床试验。与最初的试验一样，尽管多年来抗原表达技术和载体设计不断改进，但在大多数情况下，仅获得了适度的外来抗原特异性免疫。在本综述中，我们将试图通过研究人类胃肠道细菌免疫的基础以及肠道如何检测病原体与良性共生生物并作出反应，来解构载体疫苗在人类中的免疫原性。然后将探讨载体疫苗设计，以确定保留病原体尽可能多的特征以引发强大的载体和外来抗原特异性免疫，同时避免过度刺激不可接受的反应原性炎症反应的可行性。
