BCG-induced increase in interferon-gamma response to mycobacterial antigens and efficacy of BCG vaccination in Malawi and the UK: two randomised controlled studies.
BACKGROUND
The efficacy of BCG vaccines against pulmonary tuberculosis varies between populations, showing no protection in Malawi but 50-80% protection in the UK. To investigate the mechanism underlying these differences, randomised controlled studies were set up to measure vaccine-induced immune responsiveness to mycobacterial antigens in both populations.


METHODS
483 adolescents and young adults in Malawi and 180 adolescents in the UK were tested for interferon-gamma (IFN-gamma) response to M tuberculosis purified protein derivative (PPD) in a whole blood assay, and for delayed type hypersensitivity (DTH) skin test response to tuberculin PPD, before and 1 year after receiving BCG (Glaxo 1077) vaccination or placebo or no vaccine.


RESULTS
The percentages of the randomised individuals who showed IFN-gamma and DTH responses were higher in Malawi than in the UK pre-vaccination-ie, 61% (331/546) versus 22% (47/213) for IFN-gamma and 46% (236/517) versus 13% (27/211) for DTH. IFN-gamma responses increased more in the UK than in Malawi, with 83% (101/122) and 78% (251/321) respectively of the vaccinated groups responding, with similar distributions in the two populations 1 year post-vaccination. The DTH response increased following vaccination in both locations, but to a greater extent in the UK than Malawi. The IFN-gamma and DTH responses were strongly associated, except among vaccinees in Malawi.


CONCLUSIONS
The magnitude of the BCG-attributable increase in IFN-gamma responsiveness to M tuberculosis PPD, from before to 1 year post-vaccination, correlates better with the known levels of protection induced by immunisation with BCG than does the absolute value of the IFN-gamma or DTH response after vaccination. It is likely that differential sensitisation due to exposure to environmental mycobacteria is the most important determinant of the observed differences in protection by BCG between populations.
Black
Gillian F
GF
Karonga Prevention Study, Chilumba, Malawi.
Weir
Rosemary E
RE
Floyd
Sian
S
Bliss
Lyn
L
Warndorff
David K
DK
Crampin
Amelia C
AC
Ngwira
Bagrey
B
Sichali
Lifted
L
Nazareth
Bernadette
B
Blackwell
Jenefer M
JM
Branson
Keith
K
Chaguluka
Steven D
SD
Donovan
Linda
L
Jarman
Elizabeth
E
King
Elizabeth
E
Fine
Paul E M
PE
Dockrell
Hazel M
HM
D000293:Adolescent; D000328:Adult; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D008295:Malawi; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014373:Tuberculin / Q000276:immunology*; D014374:Tuberculin Test; D014376:Tuberculosis / Q000517:prevention & control*; D006113:United Kingdom
D001500:BCG Vaccine; D014373:Tuberculin; D007371:Interferon-gamma