The cytokine response to Bacille Calmette Guérin vaccination in South India

SETTING: Evaluation of immune response after BCG vaccination in a population from South India where BCG vaccination was a failure.

OBJECTIVE: To study the cell-mediated immune responses (CMI) in vitro by assessing skin test conversion, lymphocyte proliferation and cytokine patterns before and after BCG vaccination in 20 Mantoux negative subjects, and to compare this with that of 20 naturally Mantoux positive subjects.

DESIGN: In vitro lymphocyte proliferation and cytokine responses to various mycobacterial antigens were studied in 12 subjects from each group. The cytokines interferon gamma (IFN-γ), interleukin (IL)-4 and IL-10 were measured by both reverse transcriptase polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA).

RESULTS: All of those who were initially Mantoux negative but one subject converted to positivity following vaccination, confirming that BCG vaccination does cause skin test conversion. However, in vitro proliferative responses to phytohaemagglutinin (PHA), purified protein derivative (PPD) and Mycobacterium tuberculosis remained largely unaltered by vaccination. The production of IFN-γ was significantly higher in PPD-positive individuals compared to the PPD-negative group, and BCG vaccination of the latter did not change the levels of IFN-γ, IL-4 or IL-10.

CONCLUSIONS: The finding that PPD-negative individuals did not produce IFN-γ even following vaccination and skin test conversion suggests that BCG had little effect in driving the immune response towards a protective Th1 type.