Bavarian Nordic GmbH, Martinsried, Germany.
University of Zürich, Dekanat Vetsuisse-Fakultät Immunology, Zurich, Switzerland.
Front Immunol. 2022 Jun 14;13:841471. doi: 10.3389/fimmu.2022.841471. eCollection 2022.
Respiratory syncytial virus (RSV) causes a respiratory disease with a potentially fatal outcome especially in infants and elderly individuals. Several vaccines failed in pivotal clinical trials, and to date, no vaccine against RSV has been licensed. We have developed an RSV vaccine based on the recombinant Modified Vaccinia Virus Ankara-BN (MVA-RSV), containing five RSV-specific antigens that induced antibody and T-cell responses, which is currently tested in clinical trials. Here, the immunological mechanisms of protection were evaluated to determine viral loads in lungs upon vaccination of mice with MVA-RSV followed by intranasal RSV challenge. Depletion of CD4 or CD8 T cells, serum transfer, and the use of genetically engineered mice lacking the ability to generate either RSV-specific antibodies (T11µMT), the IgA isotype (IgA knockout), or CD8 T cells (β2M knockout) revealed that complete protection from RSV challenge is dependent on CD4 and CD8 T cells as well as antibodies, including IgA. Thus, MVA-RSV vaccination optimally protects against RSV infection by employing multiple arms of the adaptive immune system.
呼吸道合胞病毒（RSV）可引起呼吸道疾病，特别是对婴儿和老年人来说，可能会导致致命后果。有几种疫苗在关键性临床试验中失败了，迄今为止，还没有获得授权的 RSV 疫苗。我们基于重组改良安卡拉痘苗病毒-BN（MVA-RSV）开发了一种 RSV 疫苗，该疫苗含有五种 RSV 特异性抗原，可诱导抗体和 T 细胞反应，目前正在临床试验中进行测试。在这里，评估了免疫保护机制，以确定用 MVA-RSV 接种小鼠后，通过鼻腔 RSV 挑战，肺部的病毒载量。耗尽 CD4 或 CD8 T 细胞、血清转移以及使用缺乏产生 RSV 特异性抗体（T11µMT）、IgA 同种型（IgA 敲除）或 CD8 T 细胞（β2M 敲除）能力的基因工程小鼠，表明完全免受 RSV 挑战的保护依赖于 CD4 和 CD8 T 细胞以及抗体，包括 IgA。因此，MVA-RSV 疫苗接种通过利用适应性免疫系统的多个分支，可实现对 RSV 感染的最佳保护。
