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- Title
A T Cell-Inducing Influenza Vaccine for the Elderly: Safety and Immunogenicity of MVA-NP+M1 in Adults Aged over 50 Years.
- Authors
Antrobus, Richard D.; Lillie, Patrick J.; Berthoud, Tamara K.; Spencer, Alexandra J.; McLaren, James E.; Ladell, Kristin; Lambe, Teresa; Anita Milicic; Price, David A.; Hill, Adrian V. S.; Gilbert, Sarah C.
- 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⋅5x108 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.
- Subjects
INFLUENZA vaccination research; T cells; RESEARCH methodology; NUCLEOPROTEINS; IMMUNE response; IMMUNOSENESCENCE
- Publication
PLoS ONE, 2012, Vol 7, Issue 10, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0048322