Bandim Health Project, Bissau, Guinea-Bissau, University of Southern Denmark, Odense, Denmark; Odense Patient data Explorative Network, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Radboud Center for Infectious Diseases, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands; Department of Immunology and Metabolism, Life and Medical Science Institute, University of Bonn, Bonn, Germany.
Lancet Infect Dis. 2023 Jan;23(1):e34-e42. doi: 10.1016/S1473-3099(22)00498-4. Epub 2022 Aug 26.
Live attenuated vaccines could have beneficial, non-specific effects of protecting against vaccine-unrelated infections, such as BCG protecting against respiratory infection. During the COVID-19 pandemic, testing of these effects against COVID-19 was of interest to the pandemic control programme. Non-specific effects occur due to the broad effects of specific live attenuated vaccines on the host immune system, relying on heterologous lymphocyte responses and induction of trained immunity. Knowledge of non-specific effects has been developed in randomised controlled trials and observational studies with children, but examining of whether the same principles apply to adults and older adults was of interest to researchers during the pandemic. In this Personal View, we aim to define a framework for the analysis of non-specific effects of live attenuated vaccines against vaccine-unrelated infections with pandemic potential using several important concepts. First, study endpoints should prioritise severity of infection and overall patient health rather than incidence of infection only (eg, although several trials found no protection of the BCG vaccine against COVID-19 infection, it is associated with lower overall mortality than placebo). Second, revaccination of an individual with the same live attenuated vaccine could be the most effective strategy against vaccine-unrelated infections. Third, coadministration of several live attenuated vaccines might enhance beneficial non-specific effects. Fourth, the sequence of vaccine administration matters; the live attenuated vaccine should be the last vaccine administered before exposure to the pandemic infection and non-live vaccines should not be administered afterwards. Fifth, live attenuated vaccines could modify the immune response to specific COVID-19 vaccines. Finally, non-specific effects of live attenuated vaccines should always be analysed with subgroup analysis by sex of individuals receiving the vaccines.
减毒活疫苗可能具有有益的、非特异性的作用，可以预防与疫苗无关的感染，例如卡介苗（BCG）预防呼吸道感染。在 COVID-19 大流行期间，针对 COVID-19 测试这些效果引起了大流行控制计划的兴趣。非特异性作用是由于特定的减毒活疫苗对宿主免疫系统的广泛影响而产生的，依赖于异源淋巴细胞反应和训练免疫的诱导。非特异性效应的知识已经在针对儿童的随机对照试验和观察性研究中得到了发展，但研究人员在大流行期间对这些原理是否同样适用于成人和老年人进行了研究。在本个人观点中，我们旨在使用几个重要概念为分析具有大流行潜力的与疫苗无关的感染的减毒活疫苗的非特异性效应定义一个框架。首先，研究终点应优先考虑感染的严重程度和整体患者健康，而不仅仅是感染的发生率（例如，尽管几项试验发现卡介苗疫苗不能预防 COVID-19 感染，但它与安慰剂相比总体死亡率较低）。其次，用相同的减毒活疫苗对个体进行再接种可能是预防与疫苗无关的感染的最有效策略。第三，几种减毒活疫苗的联合使用可能会增强有益的非特异性效应。第四，疫苗接种顺序很重要；活疫苗应在接触大流行感染之前最后接种，非活疫苗不应在此之后接种。第五，活疫苗可能会改变对特定 COVID-19 疫苗的免疫反应。最后，应始终通过接受疫苗的个体的性别进行亚组分析来分析减毒活疫苗的非特异性效应。
