Efficacy and Safety of a Modified Vaccinia Ankara-NP+M1 Vaccine Combined with QIV in People Aged 65 and Older: A Randomised Controlled Clinical Trial (INVICTUS)
Chris Butler,
Chris Ellis,
Pedro M. Folegatti,
Hannah Swayze,
Julie Allen,
Louise Bussey,
Duncan Bellamy,
Alison Lawrie,
Elizabeth Eagling-Vose,
Ly-Mee Yu,
Milensu Shanyinde,
Catherine Mair,
Amy Flaxman,
Katie Ewer,
Sarah Gilbert,
Thomas G. Evans,
on behalf of the INVICTUS Investigators
Affiliations
Chris Butler
Nuffield Department of Primary Health Care Sciences, University of Oxford, Oxford OX2 6GG, UK
Chris Ellis
Vaccitech Ltd., Oxford OX4 4GE, UK
Pedro M. Folegatti
Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK
Hannah Swayze
Nuffield Department of Primary Health Care Sciences, University of Oxford, Oxford OX2 6GG, UK
Julie Allen
Nuffield Department of Primary Health Care Sciences, University of Oxford, Oxford OX2 6GG, UK
Louise Bussey
Vaccitech Ltd., Oxford OX4 4GE, UK
Duncan Bellamy
Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK
Alison Lawrie
Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK
Elizabeth Eagling-Vose
Vaccitech Ltd., Oxford OX4 4GE, UK
Ly-Mee Yu
Nuffield Department of Primary Health Care Sciences, University of Oxford, Oxford OX2 6GG, UK
Milensu Shanyinde
Nuffield Department of Primary Health Care Sciences, University of Oxford, Oxford OX2 6GG, UK
Catherine Mair
Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK
Amy Flaxman
Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK
Katie Ewer
Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK
Sarah Gilbert
Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK
Background: Pre-existing T cell responses to influenza have been correlated with improved clinical outcomes in natural history and human challenge studies. We aimed to determine the efficacy, safety and immunogenicity of a T-cell directed vaccine in older people. Methods: This was a multicentre, participant- and safety assessor-blinded, randomised, placebo-controlled trial of the co-administration of Modified Vaccinia Ankara encoding nucleoprotein and matrix protein 1 (MVA-NP+M1) and annual influenza vaccine in participants ≥ 65. The primary outcome was the number of days with moderate or severe influenza-like symptoms (ILS) during the influenza season. Results: 846 of a planned 2030 participants were recruited in the UK prior to, and throughout, the 2017/18 flu season. There was no evidence of a difference in the reported rates of days of moderate or severe ILS during influenza-like illness episodes (unadjusted OR = 0.95, 95% CI: 0.54–1.69; adjusted OR = 0.91, 95% CI: 0.51–1.65). The trial was stopped after one season due to a change in the recommended annual flu vaccine, for which safety of the new combination had not been established. More participants in the MVA-NP+M1 group had transient moderate or severe pain, redness, and systemic responses in the first seven days. Conclusion: The MVA-NP+M1 vaccine is well tolerated in those aged 65 years and over. Larger trials would be needed to determine potential efficacy.
