Research Project
3456530
Mycobacteria infections, particularly M. tuberculosis and M. avium, are now major problems in AIDS patients. In the case of M. tuberculosis, the health risk extends into the HlV-1 noninfected population. Control of mycobacterial infections is typically mediated through aggressive drug therapies but this approach has not controlled spread and antibiotic resistant variants have arisen. I propose to use a vaccine approach, based on subunit vaccine formulations, to both establish protective immunity in noninfected hosts and to increase immunity in infected individuals. The unique component of my program is the use of a plant saponin called QS-21 which has potent adjuvant activity. This adjuvant not only increases antibody responses to protein and polysaccharide antigens but also induces cell-mediated immune responses, including class I MHC antigen restricted cytotoxic T.lymphocytes. These types of cellular immune responses typically require infection with the live pathogen or a replicating vector but when the QS-21 adjuvant is used in subunit vaccines the intracellular replication step is not needed. In my studies, I propose to evaluate the QS-21 adjuvant using a mouse model in vaccine formulations containing different proteins and glycolipids from M. avium. The immune responses will be characterized and animals will be challenged to directly assess immune-mediated protection. Mice with genetic or induced immunodeficiencies will be used to evaluate selected formulations in a model that reflects AIDS. Also, selected vaccines will be used in an immunotherapeutic manner by infecting mice prior to administration of the vaccines. The overall goal is to identify one or more M. avium components that can be used in vaccine formulations with the QS-21 adjuvant to induce protective immune responses and/or increase immunity so that the pathogen can be controlled and cleared.
