重组活减毒流感疫苗病毒递呈的呼吸道合胞病毒(RSV)保守 T 细胞表位可有效诱导 RSV 特异性肺局部记忆 T 细胞,并增强流感特异性驻留记忆 T 细胞应答。
Conserved T-cell epitopes of respiratory syncytial virus (RSV) delivered by recombinant live attenuated influenza vaccine viruses efficiently induce RSV-specific lung-localized memory T cells and augment influenza-specific resident memory T-cell responses.
机构信息
Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.
Department of Immunology, Institute of Experimental Medicine, Saint Petersburg, Russia.
出版信息
Antiviral Res. 2020 Oct;182:104864. doi: 10.1016/j.antiviral.2020.104864. Epub 2020 Jun 22.
Respiratory syncytial virus (RSV) can cause recurrent infection in people because it does not stimulate a long-lived immunological memory. There is an urgent need to develop a safe and efficacious vaccine against RSV that would induce immunological memory without causing immunopathology following natural RSV infection. We have previously generated two recombinant live attenuated influenza vaccine (LAIV) viruses that encode immunodominant T-cell epitopes of RSV M2 protein in the neuraminidase or NS1 genes. These chimeric vaccines afforded protection against influenza and RSV infection in mice, without causing pulmonary eosinophilia or inflammatory RSV disease. The current study assessed the formation of influenza-specific and RSV-specific CD4 and CD8 T-cell responses in the lungs of mice, with special attention to the lung tissue-resident memory T cell subsets (T). The RSV epitopes did not affect influenza-specific CD4 effector memory T cell (Tem) levels in the lungs. The majority of these cells formed by LAIV or LAIV-RSV viruses had CD69CD103 phenotype. Both LAIV+NA/RSV and LAIV+NS/RSV recombinant viruses induced significant levels of RSV M2 epitope-specific lung-localized CD8 Tem cells expressing both CD69 and CD103 T markers. Surprisingly, the CD69CD103 influenza-specific CD8 Tem responses were augmented by the addition of RSV epitopes, possibly as a result of the local microenvironment formed by the RSV-specific memory T cells differentiating to T in the lungs of mice immunized with LAIV-RSV chimeric viruses. This study provides evidence that LAIV vector-based vaccination can induce robust lung-localized T-cell immunity to the inserted T-cell epitope of a foreign pathogen, without altering the immunogenicity of the viral vector itself.
呼吸道合胞病毒(RSV)可引起人体的反复感染,因为它不能刺激长期的免疫记忆。目前迫切需要开发一种安全有效的 RSV 疫苗,该疫苗在诱导免疫记忆的同时,不会在自然 RSV 感染后引起免疫病理学。我们之前生成了两种重组活减毒流感疫苗(LAIV)病毒,这些病毒在神经氨酸酶或 NS1 基因中编码 RSV M2 蛋白的免疫优势 T 细胞表位。这些嵌合疫苗在小鼠中提供了针对流感和 RSV 感染的保护,而不会引起肺部嗜酸性粒细胞增多或炎症性 RSV 疾病。本研究评估了 RSV 特异性和 CD4 和 CD8 T 细胞在小鼠肺部的形成,特别关注肺组织驻留记忆 T 细胞亚群(T)。RSV 表位不会影响 LAIV 或 LAIV-RSV 病毒在肺部形成的流感特异性 CD4 效应记忆 T 细胞(Tem)水平。这些细胞中的大多数通过 LAIV 或 LAIV-RSV 病毒形成,具有 CD69CD103 表型。LAIV+NA/RSV 和 LAIV+NS/RSV 重组病毒均诱导显著水平的 RSV M2 表位特异性肺驻留 CD8 Tem 细胞,表达 CD69 和 CD103 T 标志物。令人惊讶的是,加入 RSV 表位增强了 CD69CD103 流感特异性 CD8 Tem 反应,这可能是由于 RSV 特异性记忆 T 细胞在感染 LAIV-RSV 嵌合病毒的小鼠肺部分化为 T 细胞而形成的局部微环境所致。这项研究提供了证据,表明基于 LAIV 载体的疫苗接种可以诱导针对外来病原体插入 T 细胞表位的强大肺部局部 T 细胞免疫,而不会改变病毒载体本身的免疫原性。