Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in healthy adults in South Africa.
BACKGROUND
The efficacy of bacille Calmette-Guérin (BCG) may be enhanced by heterologous vaccination strategies that boost the BCG-primed immune response. One leading booster vaccine, MVA85A (where "MVA" denotes "modified vaccinia virus Ankara"), has shown promising safety and immunogenicity in human trials performed in the United Kingdom. We investigated the safety and immunogenicity of MVA85A in mycobacteria-exposed--but Mycobacterium tuberculosis-uninfected--healthy adults from a region of South Africa where TB is endemic.


METHODS
Twenty-four adults were vaccinated with MVA85A. All subjects were monitored for 1 year for adverse events and for immunological assessment.


RESULTS
MVA85A vaccination was well tolerated and induced potent T cell responses, as measured by interferon (IFN)-gamma enzyme-linked immunospot assay, which exceeded prevaccination responses up to 364 days after vaccination. BCG-specific CD4+ T cells boosted by MVA85A were comprised of multiple populations expressing combinations of IFN-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, and IL-17, as measured by polychromatic flow cytometry. IFN-gamma-expressing and polyfunctional IFN-gamma+TNF-gamma+IL-2+ CD4+ T cells were boosted during the peak BCG-specific response, which occurred 7 days after vaccination.


CONCLUSIONS
The excellent safety profile and quantitative and qualitative immunogenicity data strongly support further trials assessing the efficacy of MVA85A as a boosting vaccine in countries where TB is endemic.


BACKGROUND
ClinicalTrials.gov identifier: NCT00460590.
Hawkridge
Tony
T
South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, and School of Child and Adolescent Health, University of Cape Town, Observatory, South Africa.
Scriba
Thomas J
TJ
Gelderbloem
Sebastian
S
Smit
Erica
E
Tameris
Michele
M
Moyo
Sizulu
S
Lang
Trudie
T
Veldsman
Ashley
A
Hatherill
Mark
M
Merwe
Linda van der
Lv
Fletcher
Helen A
HA
Mahomed
Hassan
H
Hill
Adrian V S
AV
Hanekom
Willem A
WA
Hussey
Gregory D
GD
McShane
Helen
H
D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D000956:Antigens, Viral / Q000737:chemistry; D001500:BCG Vaccine / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology* / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects* / Q000276:immunology; D007371:Interferon-gamma / Q000032:analysis; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology; D012449:Safety; D013019:South Africa; D014376:Tuberculosis / Q000517:prevention & control; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus / Q000378:metabolism*
D000942:Antigens, Bacterial; D000956:Antigens, Viral; D001500:BCG Vaccine; D014614:Vaccines, Synthetic; D007371:Interferon-gamma