Статья

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

V. Matyushenko, T. Kotomina, I. Kudryavtsev, D. Mezhenskaya, P. Prokopenko, A. Matushkina, K. Sivak, A. Muzhikyan, L. Rudenko, I. Isakova-Sivak,
2021

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 (TRM). 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 CD69+CD103- phenotype. Both LAIV+NA/RSV and LAIV+NS/RSV recombinant viruses induced significant levels of RSV M282 epitope-specific lung-localized CD8 Tem cells expressing both CD69 and CD103 TRM markers. Surprisingly, the CD69+CD103+ 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 TRM 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. © 2020 Elsevier B.V.

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  • 1. Version of Record от 2021-04-27

Метаданные

Об авторах
  • V. Matyushenko
    Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russian Federation
  • T. Kotomina
    Department of Immunology, Institute of Experimental Medicine, Saint Petersburg, Russian Federation
  • I. Kudryavtsev
    Smorodintsev Research Institute of Influenza, Saint Petersburg, Russian Federation
  • D. Mezhenskaya
  • P. Prokopenko
  • A. Matushkina
  • K. Sivak
  • A. Muzhikyan
  • L. Rudenko
  • I. Isakova-Sivak
Название журнала
  • Antiviral Research
Том
  • 182
Страницы
  • -
Ключевые слова
  • alpahaE beta7integrin; CD69 antigen; epitope; immunoglobulin G; integrin; respiratory syncytial virus vaccine; sialidase; T lymphocyte antigen; unclassified drug; animal cell; animal experiment; animal model; animal tissue; Article; bronchiole; CD4+ T lymphocyte; CD8+ T lymphocyte; cellular immunity; controlled study; cytokine response; eosinophil; erythrocyte; female; HEp-2 cell line; histopathology; Human respiratory syncytial virus; immune response; influenza; Influenza A virus (H7N9); lung parenchyma; memory T lymphocyte; mononuclear cell; mouse; nonhuman; phenotype; priority journal; respiratory syncytial virus infection; spleen cell; TEM cell line; tumor microenvironment; virus immunity; virus recombinant
Издатель
  • Elsevier B.V.
Тип документа
  • journal article
Тип лицензии Creative Commons
  • CC
Правовой статус документа
  • Свободная лицензия
Источник
  • scopus