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Failure to induce enhanced protection against tuberculosis by increasing T-cell-dependent interferon-gamma generation
I S Leal1, B Smedegård, P Andersen
1Laboratory of Microbiology and Immunology of Infection, Institute for Molecular and Cell Biology, University of Porto, Porto, Portugal.
We evaluated the use of recombinant human interleukin-6 (rhIL-6) and a monoclonal antibody specific for interferon-gamma (IFN-gamma) as co-adjuvants in a subunit vaccine against tuberculosis consisting of the culture filtrate proteins of Mycobacterium tuberculosis (ST-CF) emulsified in the adjuvant dimethyl-dioctadecylammonium bromide (DDA). Both the addition of rhIL-6 and the neutralization of IFN-gamma resulted in an increased T helper type 1 (Th1) response characterized by enhanced IFN-gamma production and cell proliferation. Nevertheless, this did not result in the enhancement of protection against either an intravenous or an aerosol M. tuberculosis challenge. Our data stress the need to identify further correlates of protection in addition to IFN-gamma production to screen vaccines against tuberculosis infection.
We evaluated the use of recombinant human interleukin-6 (rhIL-6) and a monoclonal antibody specific for interferon-gamma (IFN-gamma) as co-adjuvants in a subunit vaccine against tuberculosis consisting of the culture filtrate proteins of Mycobacterium tuberculosis (ST-CF) emulsified in the adjuvant dimethyl-dioctadecylammonium bromide (DDA). Both the addition of rhIL-6 and the neutralization of IFN-gamma resulted in an increased T helper type 1 (Th1) response characterized by enhanced IFN-gamma production and cell proliferation. Nevertheless, this did not result in the enhancement of protection against either an intravenous or an aerosol M. tuberculosis challenge. Our data stress the need to identify further correlates of protection in addition to IFN-gamma production to screen vaccines against tuberculosis infection.