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lb496 |
1 South African Tuberculosis Vaccine Initiative, University of Cape Town, Cape Town, South Africa,
2 Aeras Global Tuberculosis Vaccine Foundation, Cape Town, South Africa,
3 TBRU, CWRU, Cleveland, OH,
4 PHRI, UMDNJ, newark, NJ
ABSTRACT
Objective: In HIV+ infants BCG vaccination carries a significant risk of developing BCG disease, and it is unknown whether protective immunity is induced in this immuno-compromised group. The aim of this study was to study the BCG-specific immune response in HIV+ infants, and assess the risk/benefit of vaccination.
Methods: We compared BCG-induced T cell responses longitudinally between HIV+, exposed HIV-, and HIV- infants for 1 year. Whole blood from infants at 3, 6, 9 and 12 months of age was restimulated with live BCG for 12 hours. Multiparameter flow cytometry was used to quantify T cells expressing IFNg, TNF, and IL-2. These cytokines were also measured in supernatants by ELISA.
Results: BCG vaccination of the 2 HIV- cohorts (n=27 and 23) induced a robust BCG response at 3 months, characterised by a high frequency of BCG-specific polyfunctional (IFNg+IL-2+TNF+) CD4 T cells. In contrast, the HIV+ cohort (n=18) had a very poor response. The BCG-specific CD8 T cell response, characterized predominantly by IFNg production, was also lower in the HIV+ cohort. Decreased IFNg and IL-2 levels were detected in supernatants from HIV+ infants. Immunity waned in all cohorts over the first year of life, but much more dramatically so in HIV+ infants.
Conclusions: BCG vaccination may provide minimal protective immunity in HIV+ infants, and supports the recommendation by the WHO that BCG not be given to this vulnerable group.
This study was supported by the Elizabeth Glaser Pediatric AIDS Foundation and the NIH-funded TB Research Unit.
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