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. 2021 Aug 3;9(8):851.
doi: 10.3390/vaccines9080851.

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  1 , Chris Ellis  2 , Pedro M Folegatti  3 , Hannah Swayze  1 , Julie Allen  1 , Louise Bussey  2 , Duncan Bellamy  3 , Alison Lawrie  3 , Elizabeth Eagling-Vose  2 , Ly-Mee Yu  1 , Milensu Shanyinde  1 , Catherine Mair  3 , Amy Flaxman  3 , Katie Ewer  3 , Sarah Gilbert  3 , Thomas G Evans  2 , On Behalf Of The Invictus Investigators
Affiliations

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 et al. Vaccines (Basel). .

Abstract

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.

Keywords: MVA; elderly; influenza; nucleoprotein; vaccination.

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Conflict of interest statement

T.G.E., E.E.-V., L.B. and C.E. were employed by Vaccitech Ltd., the sponsor of the study. S.G. owns stock in Vaccitech Ltd. K.R. received consultancy income from Vaccitech Ltd.

Figures

Figure 1
Figure 1
CONSORT Diagram showing patient screening and flow. ITT- intention to treat.
Figure 2
Figure 2
Local (A) and Systemic (B) reactogenicity in the 7 days following vaccination as recorded on patient diary cards.
Figure 3
Figure 3
(A). Gamma interferon ELISpot responses to NP and M1 pools A. Data over the study shown as median plus 25 and 75% intervals at days 0, 21 and 182. (B). Fold change (+SD) in responses at day 0 and 21 to the NP or M1 peptide pools. Increases were significant comparing MVA-NP+M1 to placebo for each antigen (p < 0.01). The blue line represents no change (fold increase of 1).
Figure 4
Figure 4
Influenza-specific hemagglutination geometric mean titers to the 2017 vaccine components (H1N1, H3N2, B Brisbane and B Pukhet) in the MVA (n = 26) and placebo recipients (n = 23) (SD and p values shown in Table 4); all participants received inactivated influenza vaccine.
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