Effect of high-dose vitamin A supplementation on the immune response to Bacille Calmette-Guerin vaccine.
BACKGROUND
Vitamin A supplementation (VAS) at birth has been associated with decreased mortality in Asia. Bacille Calmette-Guérin (BCG) vaccine is given at birth in tuberculosis-endemic countries. Previous studies suggest that VAS may influence the immune response to vaccines.


OBJECTIVE
Our objective was to examine whether VAS influences the immune response to simultaneously administered BCG vaccine.


METHODS
Within a randomized trial of 50,000 IU vitamin A or placebo given with BCG vaccine at birth in Guinea-Bissau, 2710 infants were examined for BCG scar formation and delayed-type hypersensitivity (DTH) to purified protein derivative of Mycobacterium tuberculosis (PPD) at 2 and 6 mo of age. The ex vivo cytokine response to PPD was measured in 607 infants.


RESULTS
At 2 mo of age, 39% (43% of the boys and 34% of the girls) responded to PPD. The prevalence ratio of a measurable PPD reaction for VAS compared with placebo recipients was 0.90 (95% CI: 0.80, 1.02) for all infants, 0.81 (95% CI: 0.69, 0.95) for boys, and 1.04 (95% CI: 0.86, 1.26) for girls. At 6 mo of age, 42% of the infants responded to PPD. No difference was observed between VAS and placebo recipients. The prevalence of BCG scar was not affected by VAS. The ex vivo interferon-gamma response to PPD was increased by VAS (means ratio: 1.40; 95% CI: 1.03, 1.91).


CONCLUSIONS
VAS with BCG vaccination does not appear to interfere with the long-term immune response to BCG. However, VAS temporarily altered the DTH reaction to PPD in boys at 2 mo of age, suggesting sex differences in the immunologic response to VAS given with BCG. This trial was registered at www.clinicaltrials.gov as #NCT00168597.
Diness
Birgitte R
BR
Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau. birgitte@diness.dk
Fisker
Ane B
AB
Roth
Adam
A
Yazdanbakhsh
Maria
M
Sartono
Erliyani
E
Whittle
Hilton
H
Nante
Jose E
JE
Lisse
Ida M
IM
Ravn
Henrik
H
Rodrigues
Amabelia
A
Aaby
Peter
P
Benn
Christine S
CS
D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D016001:Confidence Intervals; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006169:Guinea-Bissau; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000453:epidemiology / Q000276:immunology*; D007223:Infant; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016017:Odds Ratio; D015995:Prevalence; D012737:Sex Factors; D013997:Time Factors; D014373:Tuberculin / Q000276:immunology; D014801:Vitamin A / Q000008:administration & dosage* / Q000494:pharmacology
D001500:BCG Vaccine; D014373:Tuberculin; D014801:Vitamin A