HHS - National Vaccine Program Office (NVPO)

Proposal Number:	N70
PI Name:	Brennan, Michael J.
PI Email:	brennan@cber.fda.gov
PI Title:	Senior Investigator
Project Title:	Development of a novel recombinant vaccine to treat adult pulmonary tuberculosis.
Project Start:	2003
Project End:	2004

Abstract: Close to 2 million people die each year from tuberculosis (TB). An important prevention strategy is to develop new subunit vaccines that can prevent adult pulmonary TB. Our previous work has identified a cell surface protein of Mycobacterium tuberculosis (Mtb), heparin-binding hemagglutinin (HBHA) as a mycobacterial adhesin and factor important for the dissemination of Mtb to extrapulmonary sites in the host. In this project, we will investigate the immunogenic properties of HBHA and determine if it is a suitable candidate for a subunit vaccine for TB. Since recombinant HBHA expressed in E. coli cannot be used as a vaccine due to the lack of important post-translational modifications, in Aim 1, we will first construct M. smegmatis and BCG strains over-expressing HBHA and test these strains as live vaccines in the mouse aerosol challenge model for TB. In Aim 2, recombinant HBHA will be purified from promising M. smegmatis and BCG strains, adjuvanted with DDA and MPL and tested as vaccines as described above. In parallel, we will use both cytokine and ELISA assays to monitor the immunity elicited by the live and the purified recombinant HBHA subunit vaccines. In these investigations, we hope to correlate a certain pattern of immune responses against HBHA vaccines with protection. In the future, we will combine HBHA with other TB antigens that have shown promise as vaccine candidates. Vaccines containing an adhesin such as HBHA, together with antigens that provide a strong cell-mediated immunity, may provide the most effective vaccine formulation for preventing adult pulmonary tuberculosis.

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