Czerkinsky Cecil, Holmgren Jan
CNRS, INSERM, Institut de Pharmacologie Moleculaire et Cellulaire, Université Nice Sophia Antipolis, 06103 Nice, France
Department of Microbiology and Immunology, University of Gothenburg Vaccine Research Institute (GUVAX), Gothenburg 405 30, Sweden
Philos Trans R Soc Lond B Biol Sci. 2015 Jun 19;370(1671). doi: 10.1098/rstb.2015.0142.
Since the first licensure of the Sabin oral polio vaccine more than 50 years ago, only eight enteric vaccines have been licensed for four disease indications, and all are given orally. While mucosal vaccines offer programmatically attractive tools for facilitating vaccine deployment, their development remains hampered by several factors: -limited knowledge regarding the properties of the gut immune system during early life; -lack of mucosal adjuvants, limiting mucosal vaccine development to live-attenuated or killed whole virus and bacterial vaccines; -lack of correlates/surrogates of mucosal immune protection; and -limited knowledge of the factors contributing to oral vaccine underperformance in children from developing countries. There are now reasons to believe that the development of safe and effective mucosal adjuvants and of programmatically sound intervention strategies could enhance the efficacy of current and next-generation enteric vaccines, especially in lesser developed countries which are often co-endemic for enteric infections and malnutrition. These vaccines must be safe and affordable for the world's poorest, confer long-term protection and herd immunity, and must be able to contain epidemics.
自50多年前首次批准使用萨宾口服脊髓灰质炎疫苗以来,仅有8种肠道疫苗获批用于4种疾病适应症,且均为口服给药。虽然黏膜疫苗为促进疫苗接种提供了具有吸引力的工具,但其研发仍受到多种因素的阻碍:关于生命早期肠道免疫系统特性的知识有限;缺乏黏膜佐剂,将黏膜疫苗的研发限制在减毒活疫苗或灭活全病毒及细菌疫苗;缺乏黏膜免疫保护的相关指标/替代指标;以及对发展中国家儿童口服疫苗效果不佳的影响因素了解有限。现在有理由相信,开发安全有效的黏膜佐剂和合理的干预策略可以提高当前和下一代肠道疫苗的效力,尤其是在肠道感染和营养不良往往同时流行的欠发达国家。这些疫苗必须对世界上最贫困的人群安全且价格可承受,提供长期保护和群体免疫,并且必须能够控制疫情。