are named inventors on patent applications relating to RH5 and/or other malaria vaccines and immunization regimens. L. Siani and S. Di Marco are employees of ReiThera (formerly Okairos), which is currently developing vectored vaccines for a number of diseases. J. Vekemans was an employee of GSK, which has acquired the ChAd63 vector from Okairos. R. Ashfield is a director of Ducentis and holds shares in the company, which is developing a therapy for autoimmune disease. A.M. Minassian has an immediate family member who is an inventor on patents relating to RH5 and/or other malaria vaccines and immunization regimens and who is a cofounder of, shareholder in, and consultant for SpyBiotech. S. Biswas is a cofounder and CEO of, and shareholder in, SpyBiotech and is a contributor in a patent application relating to multimerisation technology. J. Jin is a cofounder of and shareholder in SpyBiotech.

BackgroundT-cell responses against highly conserved influenza antigens have been previously associated with protection. However, these immune responses are poorly maintained following recovery from influenza infection and are not boosted by inactivated influenza vaccines. We have previously demonstrated the safety and immunogenicity of two viral vectored vaccines, modified vaccinia virus Ankara (MVA) and the chimpanzee adenovirus ChAdOx1 expressing conserved influenza virus antigens, nucleoprotein (NP) and matrix protein-1 (M1). We now report on the safety and long-term immunogenicity of multiple combination regimes of these vaccines in young and older adults.MethodsWe conducted a Phase I open-label, randomized, multi-center study in 49 subjects aged 18–46 years and 24 subjects aged 50 years or over. Following vaccination, adverse events were recorded and the kinetics of the T cell response determined at multiple time points for up to 18 months.FindingsBoth vaccines were well tolerated. A two dose heterologous vaccination regimen significantly increased the magnitude of pre-existing T-cell responses to NP and M1 after both doses in young and older adults. The fold-increase and peak immune responses after a single MVA-NP + M1 vaccination was significantly higher compared to ChAdOx1 NP + M1. In a mixed regression model, T-cell responses over 18 months were significantly higher following the two dose vaccination regimen of MVA/ChAdOx1 NP + M1.InterpretationA two dose heterologous vaccination regimen of MVA/ChAdOx1 NP + M1 was safe and immunogenic in young and older adults, offering a promising vaccination strategy for inducing long-term broadly cross-reactive protection against influenza A.Funding SourceMedical Research Council UK, NIHR BMRC Oxford.