H INFLUENZAE VACCINE BASED ON RECOMBINANT BCG

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BCG (Bacille Calmette-Guerin), and attenuated strain of Mycobacterium bovis that is used in viable form to vaccinate humans against tuberculosis, offers a number of unique advantages for development as a multivalent vaccine vehicle. Recently, versatile vectors for the expression of heterologous proteins in recombinant BCG (rBCG) have been developed. To further improve the immunogenicity of heterologous antigens in rBCG we have constructed new rBCG expression vectors employing sequences encoding mycobacterial lipoproteins to effect in vivo acylation and export of recombinant antigens to the surface of rBCG. Others had previously shown that acylation can enhance the humoral and cellular responses to various proteins. Preliminary results with the recombinant lipoprotein antigen OspA of Borrelia burgdorferi show that the fusion- lipoprotein vectors can effect the desired biochemical modifications and immune response enhancement for this protein. To further test this system we propose to construct BCG recombinants expressing the highly conserved P6 lipoprotein of Haemophilus influenzae, a demonstrated target for protective antibodies. These proposed studies will provide useful insight into the potential for rBCG as a live vaccine vehicle, for the fusion- lipoprotein approach, and will also yield a new candidate vaccine for disease caused by both type b ad unencapsulated H. influenzae.