Abstracts

Mycobacterium bovis BCG heat shock protein (BCG-HSP) / ovalbumin (OVA) fusion protein is more effective than free BCG-HSP in preventing allergic airway inflammation and airway hyperresponsiveness.

Abstract presented at ATS 2001 (American Thoracic Society) - San Francisco, CA, USA May 18-23, 2001 as printed in Am J Respir Crit Care Med 2001; 163(5): 243

Rha Y.H., Joetham A., Takeda K., Duez C., Balhorn A., Dakhama A., Siegel M.I. (1), Gelfand E.W.

Dept. of Pediatrics, National Jewish Medical and Research Center, Denver, CO, USA.
(1) Stressgen Biotechnologies, Inc., Collegeville, PA, USA.

BCG-HSP has been associated with the generation and induction of Th1-type immune responses. Antigen fusion protein has recently been demonstrated to be effective as Ag specific modulators of immune responses. In this study we investigated the effects of BCG-HSP/OVA fusion protein and free BCG-HSP in a mouse model of allergic airway inflammation. HSPs were administered to each group by intraperitoneal injection 2 h before sensitization and/or challenge. Sensitized and challenged mice (IPN) developed heightened responsiveness to methacholine and increased serum levels of OVA-specific IgE with a significant airway eosinophilia when compared to non-sensitized animals. Administration of BCG-HSP/OVA significantly prevented development of AHR, IL-4 and IL-5 production and eosinophilia in BALF and OVA-specific IgE production measured in serum (p<0.05) compared with untreated mice. IFN-G production in BALF was significantly increased following treatment with BCG-HSP/OVA. In contrast, treatment with free BCG-HSP showed smaller inhibitory effects on AHR and eosinophilia or IL-4 and IL-5 production in BALF. The supernatants of OVA stimulated mononuclear cell cultures from BCG-HSP/OVA treated mice contained significantly less IL-4 and IL-5. These results indicate the efficacy of BCG-HSP/OVA fusion protein can reversing Th2 immune responses and stimulating Th1 responses in an Ag-specific manner. BCG-HSP/Ag fusion protein may be beneficial in the treatment of allergic airway inflammation and hyperresponsiveness. This abstract is funded by: NIH, HL-36577