Effect of vaccine dose on the safety and immunogenicity of a candidate TB vaccine, MVA85A, in BCG vaccinated UK adults.
OBJECTIVE
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 1×10(7) or 1×10(8)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 5×10(7)PFU MVA85A had been administered.


RESULTS
There were no serious adverse events recorded following administration of either 1×10(7) or 1×10(8)PFU of MVA85A. Systemic adverse events were more frequently reported following administration of 1×10(8)PFU of MVA85A when compared to either 5×10(7) or 1×10(7)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 1×10(8)PFU compared to the 5×10(7) and 1×10(7) doses. Additionally, a broader range of Ag85A epitopes are detected following 1×10(8)PFU of MVA85A.


CONCLUSIONS
A higher dose of 1×10(8)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.
The Jenner Institute, University of Oxford, Oxford, United Kingdom.
Ansar A
AA
Pathan
Angela M
AM
Minassian
Clare R
CR
Sander
Rosalind
R
Rowland
David W
DW
Porter
Ian D
ID
Poulton
Adrian V S
AV
Hill
Helen A
HA
Fletcher
Helen
H
McShane
D000328:Adult; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006805:Human Experimentation; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology; D014376:Tuberculosis / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D006113:United Kingdom; D019444:Vaccines, DNA; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D055815:Young Adult
C549320:MVA 85A; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D014765:Viral Vaccines; D007371:Interferon-gamma