Immunogenic and pathogenic subfractions of Coxiella burnetii, the etiological agent of Q fever, are being studied in animals and in man in order to evaluate humoral and cellular mechanisms of pathogenesis. A. Mice. Sensitive (A/J) mice develop T-cell suppression and produce anti-lipopolysaccharide (LPS) antibodies late (35 days) in a low dose phase I infection; whereas, resistant (C57BL/6J) mice do not develop T-cell suppression and they produce anti-LPS antibodies early (21 days). Some phase I cells possess an immune suppressive complex (ISC) which consists of three separable components that may not be active alone but components 1 & 2 are required for activity, and component 3 anchors 1 & 2 to the cell surface. The biological response modification (BRM) induced by the ISC favors the growth of C. burnetii while not debilitating the hosts' response to other pathogenic agents. The ISC induces T- and B-cell antigen-specific suppressors which bind antigen. A T-cell suppresses the ConA response while a B-cell suppresses responses to antigen, but in concert these cells participate in an antigen-dependent suppressor circuit. B. Subunit vaccine. Major outer membrane proteins were identified and chromosomal DNA encoding at least 5 proteins were cloned and expressed in Escherichia coli. The structure of one of these proteins may be regulated by the acid environment of the phagolysosome thus conferring acidophilic properties to the C. burnetii cell surface. A new pahse I subunit vaccine designated as cholorform-methanol residue (CMR) produced by the Salk Institute will enter preclinical trials in September 1986. Previously, we showed that the CMR vaccine was non-toxic and efficacious in animals. Significance: The objectives of this project are to define the genetic basis of susceptibility to infection in the mouse model, to characterize components of the ISC, to develop a new recombinant subunit vaccine, and test the safety and efficacy of the CMR vaccine. Accomplishment of these objectives will allow us to produce recombinant vaccine against Q fever and test the Biological Respose Modification in model systems.
| Eells, Samantha J; Bharadwa, Kiran; McKinnell, James A et al. (2014) Recurrent urinary tract infections among women: comparative effectiveness of 5 prevention and management strategies using a Markov chain Monte Carlo model. Clin Infect Dis 58:147-60 |
