Cytotoxic T-Lymphocyte Epitope Vaccination Protects against Human Metapneumovirus Infection and Disease in Mice

Suresh Mahalingam, Karen Herd, Ian Mackay, Michael Nissen, Theo Sloots, Robert Tindle

    Research output: Contribution to journalArticle

    58 Citations (Scopus)

    Abstract

    Human metapneumovirus (hMPV) has emerged as an important human respiratory pathogen causing upper and lower respiratory tract infections in young children and older adults. In addition, hMPV infection is associated with asthma exacerbation in young children. Recent epidemiological evidence indicates that hMPV may cocirculate with human respiratory syncytial virus (hRSV) and mediate clinical disease similar to that seen with hRSV. Therefore, a vaccine for hMPV is highly desirable. In the present study, we used predictive bioinformatics, peptide immunization, and functional T-cell assays to define hMPV cytotoxic T-lymphocyte (CTL) epitopes recognized by mouse T cells restricted through several major histocompatibility complex class I alleles, including HLA-A*0201. We demonstrate that peptide immunization with hMPV CTL epitopes reduces viral load and immunopathology in the lungs of hMPV-challenged mice and enhances the expression of Th1-type cytokines (gamma interferon and interleukin-12 [IL-12]) in lungs and regional lymph nodes. In addition, we show that levels of Th2-type cytokines (IL-10 and IL-4) are significantly lower in hMPV CTL epitope-vaccinated mice challenged with hMPV. These results demonstrate for the first time the efficacy of an hMPV CTL epitope vaccine in the control of hMPV infection in a murine model.
    Original languageEnglish
    Pages (from-to)2034-2044
    Number of pages11
    JournalJournal of Virology
    Volume80
    Issue number4
    DOIs
    Publication statusPublished - 2006

    Fingerprint

    Human metapneumovirus
    Metapneumovirus
    cytotoxic T-lymphocytes
    T-Lymphocyte Epitopes
    Cytotoxic T-Lymphocytes
    epitopes
    Vaccination
    vaccination
    mice
    Infection
    infection
    Human respiratory syncytial virus
    Immunization
    immunization
    cytokines
    Vaccines
    T-lymphocytes
    lungs
    peptides
    Cytokines

    Cite this

    Mahalingam, Suresh ; Herd, Karen ; Mackay, Ian ; Nissen, Michael ; Sloots, Theo ; Tindle, Robert. / Cytotoxic T-Lymphocyte Epitope Vaccination Protects against Human Metapneumovirus Infection and Disease in Mice. In: Journal of Virology. 2006 ; Vol. 80, No. 4. pp. 2034-2044.
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    abstract = "Human metapneumovirus (hMPV) has emerged as an important human respiratory pathogen causing upper and lower respiratory tract infections in young children and older adults. In addition, hMPV infection is associated with asthma exacerbation in young children. Recent epidemiological evidence indicates that hMPV may cocirculate with human respiratory syncytial virus (hRSV) and mediate clinical disease similar to that seen with hRSV. Therefore, a vaccine for hMPV is highly desirable. In the present study, we used predictive bioinformatics, peptide immunization, and functional T-cell assays to define hMPV cytotoxic T-lymphocyte (CTL) epitopes recognized by mouse T cells restricted through several major histocompatibility complex class I alleles, including HLA-A*0201. We demonstrate that peptide immunization with hMPV CTL epitopes reduces viral load and immunopathology in the lungs of hMPV-challenged mice and enhances the expression of Th1-type cytokines (gamma interferon and interleukin-12 [IL-12]) in lungs and regional lymph nodes. In addition, we show that levels of Th2-type cytokines (IL-10 and IL-4) are significantly lower in hMPV CTL epitope-vaccinated mice challenged with hMPV. These results demonstrate for the first time the efficacy of an hMPV CTL epitope vaccine in the control of hMPV infection in a murine model.",
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    Cytotoxic T-Lymphocyte Epitope Vaccination Protects against Human Metapneumovirus Infection and Disease in Mice. / Mahalingam, Suresh; Herd, Karen; Mackay, Ian; Nissen, Michael; Sloots, Theo; Tindle, Robert.

    In: Journal of Virology, Vol. 80, No. 4, 2006, p. 2034-2044.

    Research output: Contribution to journalArticle

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