Effect of vaccine dose on the safety and immunogenicity of a candidate TB vaccine, MVA85A, in BCG vaccinated UK adults

Purpose

A non-randomised, open-label, Phase I safety and immunogenicity dose-finding study to assess the safety and immunogenicity of the candidate TB vaccine Modified Vaccinia virus Ankara expressing Antigen 85A (MVA85A) from Mycobacterium tuberculosis (MTB) in healthy adult volunteers previously vaccinated with BCG.

Methods

Healthy BCG-vaccinated volunteers were vaccinated with either 1 × 10⁷ or 1 × 10⁸ PFU of MVA85A. All adverse events were documented and antigen specific T cell responses were measured using an ex vivo IFN-γ ELISPOT assay. Safety and immunogenicity were compared between the 2 dose groups and with a previous trial in which a dose of 5 × 10⁷ PFU MVA85A had been administered.

Results

There were no serious adverse events recorded following administration of either 1 × 10⁷ or 1 × 10⁸ PFU of MVA85A. Systemic adverse events were more frequently reported following administration of 1 × 10⁸ PFU of MVA85A when compared to either 5 × 10⁷ or 1 × 10⁷ PFU of MVA85A but were mild or moderate in severity and resolved completely within 7 days of immunisation. Antigen specific T cell responses as measured by the IFN-γ ELISPOT were significantly higher following immunisation in adults receiving 1 × 10⁸ PFU compared to the 5 × 10⁷ and 1 × 10⁷ doses. Additionally, a broader range of Ag85A epitopes are detected following 1 × 10⁸ PFU of MVA85A.

Conclusion

A higher dose of 1 × 10⁸ PFU of MVA85A is well-tolerated, increases the frequency of IFN-γ secreting T cells detected following immunisation and broadens the range of Ag85A epitopes detected.