A T Cell-Inducing Influenza Vaccine for the Elderly: Safety and Immunogenicity of MVA-NP+M1 in Adults Aged over 50 Years

Richard D Antrobus, Patrick J Lillie, Tamara K Berthoud, Alexandra J Spencer, James E McLaren, Kristin Ladell, Teresa Lambe, Anita Milicic, David A Price, Adrian V S Hill and Sarah C Gilbert

PLOS ONE, 2012, vol. 7, issue 10, 1-10

Abstract: Background: Current influenza vaccines have reduced immunogenicity and are of uncertain efficacy in older adults. We assessed the safety and immunogenicity of MVA-NP+M1, a viral-vectored influenza vaccine designed to boost memory T cell responses, in a group of older adults. Methods: Thirty volunteers (aged 50–85) received a single intramuscular injection of MVA-NP+M1 at a dose of 1·5×108 plaque forming units (pfu). Safety and immunogenicity were assessed over a period of one year. The frequency of T cells specific for nucleoprotein (NP) and matrix protein 1 (M1) was determined by interferon-gamma (IFN-γ) ELISpot, and their phenotypic and functional properties were characterized by polychromatic flow cytometry. In a subset of M1-specific CD8+ T cells, T cell receptor (TCR) gene expression was evaluated using an unbiased molecular approach. Results: Vaccination with MVA-NP+M1 was well tolerated. ELISpot responses were boosted significantly above baseline following vaccination. Increases were detected in both CD4+ and CD8+ T cell subsets. Clonality studies indicated that MVA-NP+M1 expanded pre-existing memory CD8+ T cells, which displayed a predominant CD27+CD45RO+CD57−CCR7− phenotype both before and after vaccination. Conclusions: MVA-NP+M1 is safe and immunogenic in older adults. Unlike seasonal influenza vaccination, the immune responses generated by MVA-NP+M1 are similar between younger and older individuals. A T cell-inducing vaccine such as MVA-NP+M1 may therefore provide a way to circumvent the immunosenescence that impairs routine influenza vaccination. Trial Registration: ClinicalTrials.gov NCT00942071

Date: 2012
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0048322

DOI: 10.1371/journal.pone.0048322

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