Mechanisms of vaccine protection in pneumococcal pneumonia

Schubert, Courtney Lynn

Mechanisms of vaccine protection in pneumococcal pneumonia

dc.contributor.advisor	Yipp, Bryan G.
dc.contributor.author	Schubert, Courtney Lynn
dc.contributor.committeemember	Leigh, Richard A.
dc.contributor.committeemember	Peters, Nathan C.
dc.date	2018-11
dc.date.accessioned	2018-06-25T14:52:27Z
dc.date.available	2018-06-25T14:52:27Z
dc.date.issued	2018-06-13
dc.description.abstract	Despite the overwhelming success of vaccination in reducing mortality due to infectious diseases, it is unknown what makes some vaccines protective while others are not. Multiple vaccine candidates have failed clinical trial regardless of the production of neutralizing antibodies, therefore there is a need to establish correlates of protection that are not antibody production. We began investigating the Pnuemovax-23 vaccine which provides well characterized protection in both mice and humans, in an attempt to determine the mechanism of vaccine protection. Instead of finding that Pneumovax-23 vaccination induces disease resistance against Streptococcus pneumoniae pneumonia through eradication of the bacteria, we found that vaccinated mice survive the pneumococcal infection via disease tolerance. Therefore, we began investigating how the survival of vaccinated mice is independent of bacterial clearance from the lungs and the spleen. The role of neutrophils was first explored since there was still robust neutrophil recruitment during infection in vaccinated mice, and neutrophils are known to regulate B cells in the spleen and produce B cell growth factors. Ultimately, we determined that despite ample neutrophil recruitment during infection, neutrophils are not mediating this disease tolerance to infection in vaccinated mice. Instead, we turned to investigate whether B cells were required for disease tolerance, where we found B1 innate B cells to be required for vaccinated mice to survive the infection. CD19-/- mice are deficient in innate cells, however still have conventional B cells and neutrophil recruitment during infection. Therefore, we have found a novel mechanism of how vaccination protects against infection, through disease tolerance of the bacterial infection. With further research into the exact mechanism of B1 cells, these findings can potentially alter the future of vaccine development for bacterial pathogens that do not yet have a protective vaccine.	en_US
dc.identifier.citation	Schubert, C. L. (2018). Mechanisms of vaccine protection in pneumococcal pneumonia (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/32001	en_US
dc.identifier.doi	http://dx.doi.org/10.11575/PRISM/32001
dc.identifier.uri	http://hdl.handle.net/1880/106775
dc.language.iso	eng
dc.publisher.faculty	Cumming School of Medicine
dc.publisher.faculty	Graduate Studies
dc.publisher.institution	University of Calgary	en
dc.publisher.place	Calgary	en
dc.rights	University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subject	Pneumonia
dc.subject	Infection
dc.subject	Neutrophil
dc.subject	Vaccine
dc.subject	Pneumococcal
dc.subject	S. pneumoniae
dc.subject	B cell
dc.subject	Disease tolerance
dc.subject.classification	Immunology	en_US
dc.title	Mechanisms of vaccine protection in pneumococcal pneumonia
dc.type	master thesis
thesis.degree.discipline	Medical Science
thesis.degree.grantor	University of Calgary
thesis.degree.name	Master of Science (MSc)
ucalgary.item.requestcopy	true