Departamento de Genética Moleculary Microbiología, Facultad de Ciencias Biológicas, Millennium Institute of Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago, Chile.
Departamento de Endocrinología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Front Immunol. 2018 Dec 6;9:2875. doi: 10.3389/fimmu.2018.02875. eCollection 2018.
The Human Respiratory Syncytial Virus (hRSV) and the Human Metapneumovirus (hMPV) are two pneumoviruses that are leading agents causing acute lower respiratory tract infections (ALRTIs) affecting young infants, the elderly, and immunocompromised patients worldwide. Since these pathogens were first discovered, many approaches for the licensing of safe and effective vaccines have been explored being unsuccessful to date. We have previously described that immunization with recombinant strains of Bacillus Calmette-Guérin (rBCG) expressing the hRSV nucleoprotein (rBCG-N) or the hMPV phosphoprotein (rBCG-P) induced immune protection against each respective virus. These vaccines efficiently promoted viral clearance without significant lung damage, mainly through the induction of a T helper 1 cellular immunity. Here we show that upon viral challenge, rBCG-immunized mice developed a protective humoral immunity, characterized by production of antibodies specific for most hRSV and hMPV proteins. Further, isotype switching from IgG1 to IgG2a was observed in mice immunized with rBCG vaccines and correlated with an increased viral clearance, as compared to unimmunized animals. Finally, sera obtained from animals immunized with rBCG vaccines and infected with their respective viruses exhibited virus neutralizing capacity and protected mice from viral replication and pulmonary disease. These results support the notion that the use of rBCG strains could be considered as an effective vaccination approach against other respiratory viruses with similar biology as hRSV and hMPV.
人呼吸道合胞病毒(hRSV)和人偏肺病毒(hMPV)是两种引起急性下呼吸道感染(ALRTIs)的肺炎病毒,影响全球的婴幼儿、老年人和免疫功能低下的患者。自这些病原体首次被发现以来,已经探索了许多安全有效的疫苗许可方法,但迄今为止都没有成功。我们之前曾描述过,用表达 hRSV 核蛋白(rBCG-N)或 hMPV 磷蛋白(rBCG-P)的重组卡介苗(rBCG)菌株免疫可诱导针对每种病毒的免疫保护。这些疫苗有效地促进了病毒清除,而不会对肺部造成明显损害,主要是通过诱导 T 辅助 1 细胞免疫。在这里,我们表明,在病毒攻击后,rBCG 免疫的小鼠产生了保护性的体液免疫,其特征是产生针对大多数 hRSV 和 hMPV 蛋白的特异性抗体。此外,与未免疫的动物相比,用 rBCG 疫苗免疫的小鼠观察到 IgG1 向 IgG2a 的同种型转换,并与病毒清除增加相关。最后,从用 rBCG 疫苗免疫并感染其各自病毒的动物获得的血清显示出病毒中和能力,并保护小鼠免受病毒复制和肺部疾病的侵害。这些结果支持了这样的观点,即使用 rBCG 菌株可以被认为是针对具有与 hRSV 和 hMPV 相似生物学特性的其他呼吸道病毒的有效疫苗接种方法。
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