Benedicto-Matambo Prisca, Bines Julie E, Malamba-Banda Chikondi, Shawa Isaac T, Barnes Kayla, Kamng'ona Arox W, Hungerford Daniel, Jambo Kondwani C, Iturriza-Gomara Miren, Cunliffe Nigel A, Flanagan Katie L, Jere Khuzwayo C
Virology Research Group, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre 312225, Malawi.
Centre for Global Vaccine Research, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L69 7BE, UK.
Vaccines (Basel). 2022 Mar 10;10(3):418. doi: 10.3390/vaccines10030418.
Following the introduction of live-attenuated rotavirus vaccines in many countries, a notable reduction in deaths and hospitalisations associated with diarrhoea in children <5 years of age has been reported. There is growing evidence to suggest that live-attenuated vaccines also provide protection against other infections beyond the vaccine-targeted pathogens. These so called off-target effects of vaccination have been associated with the tuberculosis vaccine Bacille Calmette Guérin (BCG), measles, oral polio and recently salmonella vaccines, and are thought to be mediated by modified innate and possibly adaptive immunity. Indeed, rotavirus vaccines have been reported to provide greater than expected reductions in acute gastroenteritis caused by other enteropathogens, that have mostly been attributed to herd protection and prior underestimation of rotavirus disease. Whether rotavirus vaccines also alter the immune system to reduce non targeted gastrointestinal infections has not been studied directly. Here we review the current understanding of the mechanisms underlying off-target effects of vaccines and propose a mechanism by which the live-attenuated neonatal rotavirus vaccine, RV3-BB, could promote protection beyond the targeted pathogen. Finally, we consider how vaccine developers may leverage these properties to improve health outcomes in children, particularly those in low-income countries where disease burden and mortality is disproportionately high relative to developed countries.
在许多国家引入减毒活轮状病毒疫苗后，有报告称5岁以下儿童因腹泻导致的死亡和住院人数显著减少。越来越多的证据表明，减毒活疫苗除了能针对疫苗靶向病原体提供保护外，还能抵御其他感染。这些所谓的疫苗脱靶效应与卡介苗（BCG）、麻疹、口服脊髓灰质炎疫苗以及最近的沙门氏菌疫苗有关，并且被认为是由先天性免疫的改变以及可能的适应性免疫介导的。事实上，据报道轮状病毒疫苗对其他肠道病原体引起的急性肠胃炎的减少幅度超过预期，这主要归因于群体免疫保护以及之前对轮状病毒疾病的低估。轮状病毒疫苗是否也会改变免疫系统以减少非靶向性胃肠道感染尚未得到直接研究。在此，我们综述了目前对疫苗脱靶效应潜在机制的理解，并提出一种机制，通过该机制减毒活新生儿轮状病毒疫苗RV3-BB可以在靶向病原体之外提供保护。最后，我们探讨疫苗研发者如何利用这些特性来改善儿童的健康状况，尤其是那些低收入国家的儿童，在这些国家，疾病负担和死亡率相对于发达国家过高。
