Boosting BCG strategy for tuberculosis

Mycos Research, Llc, Loveland CO

Investigators

Abstract

[unreadable] DESCRIPTION (provided by applicant): The objective of this Phase I proposal is to determine if pools of purified recombinant immunogenic proteins of Mycobacterium tuberculosis can be used as boosting vaccines in people already previously vaccinated with BCG. This concept has arisen from the demonstration by several laboratories, including our collaborators at Colorado State University and at Corixa Corporation, that the effects of BCG vaccination can be enhanced by prime/boost strategies. To address this issue in this proposal, we have identified recombinant proteins that induce strong gamma interferon responses by T cells harvested from infected mice, and intend to use them, delivered in a strong TH1-directed adjuvant, to demonstrate that they can improve the resistance of BCG-vaccinated guinea pigs against aerosol challenge infection with virulent M. tuberculosis. Two pools of proteins will be initially tested; the first are immunogenic proteins found in the mid-log phase culture filtrate pool, and the second [more experimental] pool are proteins expressed by the bacillus when exposed to stress [low oxygen] conditions. Proof of principle will be determined by the demonstration that the boosting strategy will decrease the bacterial load in the lungs, improve lung immunopathology, and/or lengthen animal survival times. The long term goal is to produce a new boosting vaccine for tuberculosis consisting of pools of key immunogenic recombinant proteins. [unreadable] [unreadable]