Comparative analysis of humoral and cellular immunity induced by C. burnetii whole cell vaccines : a dissertation /
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| Format: | Thesis Book |
| Language: | English |
| Published: |
[College Station, Tex.] :
[Texas A&M University System Health Science Center],
[2011]
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| Subjects: |
| Abstract: | ABSTRACT: Coxiella burnetii is an obligate Gram-negative intracellular bacterium that causes acute Q fever and chronic infections in humans. An effective formalin killed whole cell vaccine (Q-Vax®), in use in Australia, is administered to individuals that are skin test and serologically negative. Vaccination can result in severe local or systemic adverse reaction, especially when administered to previously infected populations, and repeat vaccination can induce severe persistent reactions. Several other vaccines including inactivated Nine Mile I reference whole cell vaccines (Phase I-WCV) its derivative Phase II-W have been developed and tested in animal models. Previous study suggested that PI-WCV was more protective than PII-WCV against virulent bacterium challenge in a guinea pig and both humoral and cellular immunity are critical for vaccine derived C. burnetii protective immunity. In order to gain a better understanding of vaccine mediated protective immunity, we designed a series of experiments to dissect protective immune components through comparative analysis of PI-WCV and PII-WCV induced immune responses. First, by using C. burnetii protein microarray, we were able to decipher detailed IgG antibody profiles and make side-by-side comparison of humoral immune responses induced by PI-WCV and PII-WCV in mice. The overall IgG responding profiles were similar in these two vaccine induced sera and only identified differential immunodominant antigen was bacterial lipopolysaccharide (LPS). Although there were no major immunodominant protein antigen difference between PI-WCV and PII-WCV, we did see a higher overall IgG responses in PI-WCV immunization derived sera. Next, we analyzed the magnitude of CD4⁺ T cell responses induced by these two vaccines. By using newly identified C. burnetii H-2 I-A(superscript ♭) restricted T cell epitopes and several functional assays, we found that, comparing to PII-WCV, PI-WCV induced more cytokine producing CD4⁺ T cells (IFN-y, IL-2, and TNF-(alpha)) and these cells also had superior ability for secreting effector cytokines. Last, we compared APC responses upon stimulation with different vaccine antigens. Surprisingly, PI-WCV stimulated mBMDCs had more surface maturation marker CCR7 expression and better migratory ability than those induced by PII-WCV. In vivo functional assays further confirmed that better migration of PI-WCV treated mBMDCs correlated with more antigen presentation and T cell activation. These results may at least partially explain our observation, that higher humoral and cellular immunity are induced by PI-WCV immunization. Based on these results, we postulate that the PI-LPS or other undefined surface structure from phase I organism may trigger some unique host signaling pathway and serve as critical adjuvant for efficacious PI-WCV. |
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| Item Description: | Vita. "Major Subject: Medical Sciences". "Submitted to the Office of Research and Graduate Studies of the Texas A&M Health Science Center in partial fulfillment of the requirements for the degree of Doctor of Philosophy March 2011." "Approved as to style and content by: James E. Samuel, David McMurray, Robert C. Alaniz, Waithaka Mwangi, James E. Samuel, May 2010." |
| Physical Description: | x, 105 leaves : illustrations ; 28 cm. |
| Bibliography: | Includes bibliographical references (leaves 91-104). |