Advisory Committee Chair
David Briles
Advisory Committee Members
Scott Barnum
Susan Hollingshead
Richard Morrison
Moon Nahm
Frederik Van Ginkel
Document Type
Dissertation
Date of Award
2007
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. S. pneumoniae is a leading cause of pneumonia, meningitis, septicemia, and otitis media. Although all age groups can be affected, children and the elderly are espccially susceptible to infection. Currently there is a conjugate vaccine available for use, but this vaccine only contains capsular polysaccahride antigens from the seven most prevelant S. pneumoniae serotypes. The use of the conjugate vaccine has led to serotype shift, with more disease being caused by non-vaccine serotype bacteria. The studies presented in this dissertation identify and characterize a novel S. penumoniae vaccine candidate antigen. Pneumococcal choline-binding protein A (PcpA) is a leucine rich repeat protein. We wanted to know PcpA’s role in virulence, and we also wanted to know if it could provide protection against infection. Studies using mouse models of lung infection and fatal sepsis were used to determine if immunization with PcpA could elicit protective immunity. In our model of lung infection, active systemic and mucosal immunizations were able to significantly reduce bacterial counts from the lung homogenates of immunized mice compared to unimmunized mice. In our model of fatal sepsis, active systemic immunization significantly extended iii the survival times of immunized mice compared to unimmunized mice. The protection elicited by PcpA immunization was not serotype specific, PcpA immunization elicited significant protection against five capsular serotypes tested in our models. We also preformed studies aimed at further characterizing PcpA. We conclusively identified PcpA as a surface antigen. In addition we identified an in vitro function of PcpA. In adherence assays bacteria expressing PcpA on their surface adhered to a greater degree to lung epithelial cell monolayers than did either bacteria not expressing PcpA or mutant bacteria unable to express PcpA. This adherence appeared to be site-specific there was no difference in adherence in any of the bacterial preparations when using nasal epithelial cell monolayers. Our data strongly suggests that PcpA is a lung specific adhesin, and it also suggests that PcpA would be an effective S. pneumoniae vaccine antigen.
Recommended Citation
Glover, David Tawayne, "Pneumococcal Choline-Binding Protein A: Its Role In Virulence And Its Utility As A Streptococcus Pneumoniae Vaccine Antigen" (2007). All ETDs from UAB. 3704.
https://digitalcommons.library.uab.edu/etd-collection/3704