Our overall aim is to develop a novel approach to the prevention and therapy of Mycobacterium tuberculosis infections. We have generated murine monoclonal antibodies that recognize surface antigens of M. tuberculosis and identified one of them as protective in a mouse model.
The aims of this project are: 1) to define the relationship between antibody isotype and biological efficacy; 2) to establish the mechanism(s) of antibody-mediated protection (or enhancement) in M. tuberculosis infection; 3) to study the interaction of monoclonal antibodies with cell-mediated immunity. The experimental approach will be: to generate switch variants of the protective monoclonal antibody; test the ability of these reagents to prolong survival and decrease organ mycobacterial burden in a mouse model; study the mechanisms by which they exert their biological functions using in-vivo and in-vitro studies; and study their interaction with cell-mediated immunity using in-vivo and in-vitro studies. This study will help us understand the structural characteristics required for useful antibodies to M. tuberculosis.
|Al-Sayyed, Ban; Piperdi, Sajida; Yuan, Xinni et al. (2007) Monoclonal antibodies to Mycobacterium tuberculosis CDC 1551 reveal subcellular localization of MPT51. Tuberculosis (Edinb) 87:489-97|
|Glatman-Freedman, Aharona (2006) The role of antibody-mediated immunity in defense against Mycobacterium tuberculosis: advances toward a novel vaccine strategy. Tuberculosis (Edinb) 86:191-7|
|Lang, Mark L; Glatman-Freedman, Aharona (2006) Do CD1-restricted T cells contribute to antibody-mediated immunity against Mycobacterium tuberculosis? Infect Immun 74:803-9|
|Glatman-Freedman, Aharona; Casadevall, Arturo; Dai, Zongdong et al. (2004) Antigenic evidence of prevalence and diversity of Mycobacterium tuberculosis arabinomannan. J Clin Microbiol 42:3225-31|
|Navoa, Josephine Anne D; Laal, Suman; Pirofski, Liise-Anne et al. (2003) Specificity and diversity of antibodies to Mycobacterium tuberculosis arabinomannan. Clin Diagn Lab Immunol 10:88-94|
|Glatman-Freedman, Aharona (2003) Advances in antibody-mediated immunity against Mycobacterium tuberculosis: implications for a novel vaccine strategy. FEMS Immunol Med Microbiol 39:9-16|
|Schwebach, J Reid; Chen, Bing; Glatman-Freedman, Aharona et al. (2002) Infection of mice with aerosolized Mycobacterium tuberculosis: use of a nose-only apparatus for delivery of low doses of inocula and design of an ultrasafe facility. Appl Environ Microbiol 68:4646-9|
|Schwebach, J Reid; Glatman-Freedman, Aharona; Gunther-Cummins, Leslie et al. (2002) Glucan is a component of the Mycobacterium tuberculosis surface that is expressed in vitro and in vivo. Infect Immun 70:2566-75|
|Glatman-Freedman, A; Mednick, A J; Lendvai, N et al. (2000) Clearance and organ distribution of Mycobacterium tuberculosis lipoarabinomannan (LAM) in the presence and absence of LAM-binding immunoglobulin M. Infect Immun 68:335-41|