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. 2019 Mar 22;7(1):33.
doi: 10.3390/vaccines7010033.

Safety and Immunogenicity of the Heterosubtypic Influenza A Vaccine MVA-NP+M1 Manufactured on the AGE1.CR.pIX Avian Cell Line

Pedro M Folegatti  1 , Duncan Bellamy  2 , Amy Flaxman  3 , Catherine Mair  4 , Chris Ellis  5 , Raquel L Ramon  6 , Fernando Ramos Lopez  7 , Celia Mitton  8 , Megan Baker  9 , Ian Poulton  10 , Alison Lawrie  11 , Rachel Roberts  12 , Angela Minassian  13 , Katie J Ewer  14 , Thomas G Evans  15 , Adrian V S Hill  16 , Sarah C Gilbert  17
Affiliations

Safety and Immunogenicity of the Heterosubtypic Influenza A Vaccine MVA-NP+M1 Manufactured on the AGE1.CR.pIX Avian Cell Line

Pedro M Folegatti et al. Vaccines (Basel). .

Abstract

Seasonal influenza infections have a significant global impact leading to increased health and economic burden. The efficacy of currently available seasonal influenza vaccines targeting polymorphic surface antigens has historically been suboptimal. Cellular immune responses against highly conserved Influenza A virus antigens, such as nucleoprotein (NP) and matrix protein-1 (M1), have previously been shown to be associated with protection from disease, whilst viral-vectored vaccines are an effective strategy to boost cell-mediated immunity. We have previously demonstrated that MVA encoding NP and M1 can induce potent and persistent T cell responses against influenza. In this Phase I study, we evaluated the safety and immunogenicity of MVA-NP+M1, which was newly manufactured on an immortalized cell line, in six healthy adult participants. The vaccine was well-tolerated with only mild to moderate adverse events that resolved spontaneously and were comparable to previous studies with the same vaccine manufactured in chick embryo fibroblasts. A significant increase in vaccine-specific T cell responses was detected seven days after immunization and was directed against both antigens in the vector insert. This small Phase I study supports progression of this vaccine to a Phase IIb study to assess immunogenicity and additional protective efficacy in older adults receiving licensed seasonal influenza vaccines.

Keywords: heterosubtypic vaccine; immunogenicity; influenza; safety; viral vectors.

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Conflict of interest statement

T.G.E is the Chief Executive Officer and Board Director for Vaccitech Ltd. C.E. is the Chief Operating Officer for Vaccitech Ltd. AV.S.H and S.C.G scientific co-founders of, advisors to and shareholders in Vaccitech Ltd.

Figures

Figure 1
Figure 1
CONSORT flow diagram of the trial.
Figure 2
Figure 2
(a) Local and (b) systemic adverse events recorded after vaccination with a single dose of MVA-NP+M1.
Figure 3
Figure 3
Ex vivo IFN-γ ELISpot responses to influenza antigens NP and M1 at baseline (D0), D7 and D21 post intramuscular vaccination with MVA-NP+M1 (1.5 × 108 pfu) manufactured on AGE1.CR.pIX cell line. (a) Summed total response to NP and M1 from individual subjects. Comparisons across timepoints measured by Dunn’s multiple comparison tests; (b) responses to individual antigens, compared at each time point with two-tailed Wilcoxon signed-rank test; (c) median total responses to NP and M1 for individuals shown in (a) compared with those from a previous trial in which 21 volunteers received MVA-NP+M1 (1.5 × 108 pfu) manufactured on CEF cell line [10]. Error bars are interquartile ranges; (d) area-under-curve (AUC) analysis of data in (c). The Mann–Whitney test was used to compare the two groups; ”ns”, not statistically significant (p > 0.05).
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