Heterologous Two-Dose Vaccination with Simian Adenovirus and Poxvirus Vectors Elicits Long-Lasting Cellular Immunity to Influenza Virus A in Healthy Adults

Abstract

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.

The Design and Development of a Multi-HBV Antigen Encoded in Chimpanzee Adenoviral and Modified Vaccinia Ankara Viral Vectors; A Novel Therapeutic Vaccine Strategy against HBV

“…MVA vectored vaccines have been shown to boost the magnitude of adenoviral vaccine-induced T cell responses to several immunogens in mice [34][35][36] and humans [8,[37][38][39][40][41]. We therefore designed an MVA encoding SIi-CP mut TPA-S (sh) for use in a heterologous boost regimen following ChAdOx1-SP-SIi-CP mut TPA-S (sh) prime vaccination.…”

Humoral Immunogenicity and Efficacy of a Single Dose of ChAdOx1 MERS Vaccine Candidate in Dromedary Camels

“…ChAdOx1 MERS was generated by inserting the full length of the spike gene, from a MERS-CoV isolate (Genbank accession number: KJ650098.1), into the genome of the replication deficient ChAdOx1 vector as described previously 30,32 . The ChAdOx1 viral vector of this vaccine is replication-deficient and has been assessed in different animal models, including dromedaries 33 , and in human clinical trials 34,35 . Here, we evaluated the immunogenicity and efficacy of ChAdOx1 MERS in dromedaries that are either seropositive or seronegative for MERS-CoV.…”

Vaccine platforms for the prevention of Lassa fever

“…All immunisation regimens were found to boost pre-existing levels of T cells at all ages. Greater amplification was observed after heterologous prime-boost vaccination than after prime-only vaccination [113].…”

“…Safety evaluations of ChAdOx1 in humans have been completed for influenza (ChAdOx1 NP + M1) in younger and older adults [112,113]. In a phase I randomised-controlled trial with 49 individuals aged 18-46 years and 24 individuals aged 50 years or above, younger adults received one of four heterologous prime-boost immunisation regimens: ChAdOx1 NP + M1 and MVA-NP + MI given eight weeks apart (n = 12), ChAdOx1 NP + M1 and MVA-NP + MI given 52 weeks apart (n = 12), MVA-NP + M1 and ChAdOx1 NP + M1 given eight weeks apart (n = 13), or MVA-NP + M1 and ChAdOx1 NP + M1 given 52 weeks apart (n = 12).…”