Journal Article

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

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

2012

Overview

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. Thirty volunteers (aged 50-85) received a single intramuscular injection of MVA-NP+M1 at a dose of 1·5×10(8) 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. 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. 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. ClinicalTrials.gov NCT00942071.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adults / Age groups / Aged / Aged, 80 and over / Amino Acid Sequence / Antigens / Biological response modifiers / Biology / CC chemokine receptors / CCR7 protein / CD27 antigen / CD4 antigen / CD57 antigen / CD8 antigen / Cytokines / Cytometry / Enzyme-linked immunosorbent assay / Female / Flow cytometry / Gene expression / Geriatrics / Hepatitis / Humans / Immune response / Immune system / Immunogenicity / Immunological memory / Immunosenescence / Infections / Influenza / Influenza A Virus, H3N2 Subtype - chemistry / Influenza A Virus, H3N2 Subtype - immunology / Influenza vaccines / Interferon / Interferon-gamma - metabolism / Lymphocytes / Lymphocytes T / Male / Matrix protein / Medical research / Medicine / Memory cells / Middle Aged / Molecular Sequence Data / Nucleoproteins - immunology / Older people / Orthomyxoviridae - chemistry / Orthomyxoviridae - immunology / Safety / T cell receptors / T cells / T-cell receptor / T-Lymphocytes - immunology / T-Lymphocytes - metabolism / Vaccination / Vaccines / Vaccinia virus - chemistry / Viral infections / Viral Proteins - immunology / Viral Vaccines - adverse effects / Viral Vaccines - immunology / Viruses / γ-Interferon