Grupo de Genetica de Micobacterias, Departamento de Microbiología y Medicina Preventiva, Facultad de Medicina, Universidad de Zaragoza, IIS-Aragón, Zaragoza 50009, Spain; CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
Translational Pediatrics and Infectious Diseases, Pediatrics Department, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain; GENVIP Research Group (www.genvip.org), Instituto de Investigación Sanitaria de Santiago (SERGAS), University of Santiago de Compostela, Galicia, Spain.
EBioMedicine. 2021 Mar;65:103254. doi: 10.1016/j.ebiom.2021.103254. Epub 2021 Mar 9.
The Bacillus Calmette-Guérin (BCG), the only vaccine against tuberculosis (TB) currently in use, has shown beneficial effects against unrelated infections and to enhance immune responses to vaccines. However, there is little evidence regarding the influence of BCG vaccination on pertussis.
Here, we studied the ability of BCG to improve the immune responses to diphtheria, tetanus, and acellular (DTaP) or whole-cell pertussis (DTwP) vaccination in a mouse model. We included MTBVAC, an experimental live-attenuated vaccine derived from Mycobacterium tuberculosis, in our studies to explore if it presents similar heterologous immunity as BCG. Furthermore, we explored the potential effect of routine BCG vaccination on pertussis incidence worldwide.
We found that both BCG and MTBVAC when administered before DTaP, triggered Th1 immune responses against diphtheria, tetanus, and pertussis in mice. Immunization with DTaP alone failed to trigger a Th1 response, as measured by the production of IFN-γ. Humoral responses against DTaP antigens were also enhanced by previous immunization with BCG or MTBVAC. Furthermore, exploration of human epidemiological data showed that pertussis incidence was 10-fold lower in countries that use DTaP and BCG compared to countries that use only DTaP.
BCG vaccination may have a beneficial impact on the protection against pertussis conferred by DTaP. Further randomized controlled trials are needed to properly define the impact of BCG on pertussis incidence in a controlled setting. This could be a major finding that would support changes in immunization policies.
This work was supported by the Ministry of "Economía y Competitividad"; European Commission H2020 program, "Gobierno de Aragón"; CIBERES; "Fundação Butantan"; Instituto de Salud Carlos III and "Fondo FEDER".
卡介苗（BCG）是唯一用于预防结核病（TB）的疫苗，它对相关感染具有有益的影响，并能增强对疫苗的免疫应答。然而，关于卡介苗接种对百日咳的影响，目前证据较少。
在这里，我们研究了 BCG 在小鼠模型中对白喉、破伤风和无细胞（DTaP）或全细胞百日咳（DTwP）疫苗免疫反应的改善作用。我们还包括 MTBVAC，这是一种源自结核分枝杆菌的实验性减毒活疫苗，以探索其是否具有与 BCG 相似的异源免疫作用。此外，我们还探索了全球常规 BCG 接种对百日咳发病率的潜在影响。
我们发现，BCG 和 MTBVAC 在接种 DTaP 之前接种，均可在小鼠中引发针对白喉、破伤风和百日咳的 Th1 免疫应答。单独接种 DTaP 未能触发 Th1 反应，如 IFN-γ 的产生所衡量的。BCG 或 MTBVAC 免疫接种前，对 DTaP 抗原的体液反应也得到了增强。此外，对人类流行病学数据的探索表明，与仅使用 DTaP 的国家相比，使用 DTaP 和 BCG 的国家百日咳发病率降低了 10 倍。
BCG 接种可能对 DTaP 提供的百日咳保护产生有益影响。需要进一步的随机对照试验来正确定义 BCG 对控制环境中百日咳发病率的影响。这可能是一个重大发现，将支持免疫接种政策的改变。
这项工作得到了“Economía y Competitividad”部；欧洲委员会 H2020 计划；“Gobierno de Aragón”；CIBERES；“Fundación Butantan”；西班牙卡洛斯三世卫生研究所和“Fondo FEDER”的支持。
