Mechanisms of vaccine protection in pneumococcal pneumonia
Date
2018-06-13
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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.
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Pneumonia, Infection, Neutrophil, Vaccine, Pneumococcal, S. pneumoniae, B cell, Disease tolerance
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