The Mycobacterial Heparin-Binding Hemagglutinin Is a Protective Antigen in the Mouse Aerosol Challenge Model of Tuberculosis

• DOI: 10.1128/iai.72.12.6799-6805.2004
• Publication Date: 2004-11-23T00:37:46Z
• Authors: Marcela Parra; Thames Pickett; Giovanni Delogu; Veerabadran Dheen...; Anne-Sophie Debrie; Camille Locht; Michael J. Brennan
• Keywords: Tuberculosis vaccines

ABSTRACT The heparin-binding hemagglutinin (HBHA) of Mycobacterium tuberculosis is a surface-expressed adhesin that can affect binding to host cells via unique, methylated, carboxyl-terminal, lysine-, alanine-, and proline-rich repeat region. It has been implicated in extrapulmonary dissemination M. from the lung following initial infection host. To assess vaccine potential this protein, purified preparations HBHA were emulsified dimethyldioctadecylammonium bromide-monophosphoryl lipid A adjuvant tested for ability reduce mouse aerosol challenge model tuberculosis. HBHA-containing gave ∼0.7-log reduction CFU both lungs spleens compared controls 28 days challenge. Although notable level serum antibody was elicited after three immunizations antibodies able bind surface , passive immunization with monoclonal directed against did not protect model. Compared controls, an elevated gamma interferon response generated by splenic lymph node-derived T immunized mice presence macrophages pulsed or infected live suggesting effective immunity may be cell mediated. Efforts construct recombinant vaccines fast-growing smegmatis have unsuccessful so far, which indicates distinctive posttranslational modifications present protein expressed are critical generating immune responses. studies described here demonstrate promising new candidate