Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans.
Protective immunity against Mycobacterium tuberculosis depends on the generation of a T(H)1-type cellular immune response, characterized by the secretion of interferon-gamma (IFN-gamma) from antigen-specific T cells. The induction of potent cellular immune responses by vaccination in humans has proven difficult. Recombinant viral vectors, especially poxviruses and adenoviruses, are particularly effective at boosting previously primed CD4(+) and CD8(+) T-cell responses against a number of intracellular pathogens in animal studies. In the first phase 1 study of any candidate subunit vaccine against tuberculosis, recombinant modified vaccinia virus Ankara (MVA) expressing antigen 85A (MVA85A) was found to induce high levels of antigen-specific IFN-gamma-secreting T cells when used alone in bacille Calmette-Guerin (BCG)-naive healthy volunteers. In volunteers who had been vaccinated 0.5-38 years previously with BCG, substantially higher levels of antigen-specific IFN-gamma-secreting T cells were induced, and at 24 weeks after vaccination these levels were 5-30 times greater than in vaccinees administered a single BCG vaccination. Boosting vaccinations with MVA85A could offer a practical and efficient strategy for enhancing and prolonging antimycobacterial immunity in tuberculosis-endemic areas.
McShane
Helen
H
Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, UK. Helen.mcshane@ndm.ox.ac.uk
Pathan
Ansar A
AA
Sander
Clare R
CR
Keating
Sheila M
SM
Gilbert
Sarah C
SC
Huygen
Kris
K
Fletcher
Helen A
HA
Hill
Adrian V S
AV
D000217:Acyltransferases / Q000276:immunology*; D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018604:Epitope Mapping; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology* / Q000378:metabolism
D000942:Antigens, Bacterial; D032581:Tuberculosis Vaccines; D014614:Vaccines, Synthetic; D007371:Interferon-gamma; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis