The objectives of this project in this reporting period were i) the evaluation of the safety and immunogenicity of the Francisella tularensis live vaccine in human subjects, ii) to study the changes in murine splenic and thymic lymphoid populations after injection with Coxiella burnetii antigens, iii) the evaluation of C. burnetii lipopolysaccharide (LPS) and protein antigens as vaccines against Q fever, and iv) to study the humoral antibody immune response of humans naturally infected with C. burnetii. A. The scarification vaccination of humans with F. tularensis produced mild local reactions at the inoculation site, a significant rise in specific IgA, IgG and IgM antibodies, and a marked increase in lymphocytes responding to specific F. tularensis antigens. B. The injection of mice with phase I C. burnetii whole cells induced significant lymphocyte immunosuppression to mitogens and antigens without a significant change in antibody levels. The whole cell antigen apparently activated resident suppressor T cells rather than induce an increase in the number of Lyt-2 cells. C. Although the LPS was effective as a protective antigen, a major surface protein was more protective than LPS. D. The analysis of a specific humoral immune response by immunoblotting with human Q fever sera revealed that IgM was the first antibody to be produced, then IgG and IgA. The early detection of IgM and IgG to phase I and II whole cells in acute Q fever contrasted sharply with the lack of IgA antibodies against the LPS. Significance. i) The intradermal administration of the F. tularensis live vaccine to humans appears to be safe and it induced significant cell-mediated and humoral immune responses, ii) The suppression of cell-mediated immune responses after the injection of mice with phase I whole cells is unique in that it activates resident suppressor cells rather than altering the balance of suppressors and helpers, iii) Protein antigens of C. burnetii are effective vaccines against Q fever in mice, iv) detection of specific antibodies against several proteins but not of antibodies against the phase I lipopolysaccharide by immunoblotting distinguishes acute from chronic Q fever.
| 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 |
