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Title page for ETD etd-06182015-130009


Type of Document Dissertation
Author Wen, Sherry Cai
Author's Email Address sherrywen14@gmail.com
URN etd-06182015-130009
Title Immunity and Protection against Human Metapneumovirus
Degree PhD
Department Microbiology and Immunology
Advisory Committee
Advisor Name Title
Luc Van Kaer Committee Chair
John V. Williams Committee Member
Kelli L. Boyd Committee Member
R. Stokes Peebles Committee Member
Terence S. Dermody Committee Member
Keywords
  • NK cells
  • VLP
  • vaccines
  • CD8+ T cells
  • human metapneumovirus
Date of Defense 2015-06-05
Availability unrestricted
Abstract
My thesis project explores the NK cell response to HMPV infection, as well as the CD8+ T cell (TCD8) response to virus-like particle (VLP) vaccination. I show that while activated lung NK cell numbers increase after human metapneumovirus (HMPV) infection, and these cells degranulate and produce IFNγ, NK cell depletion does not alter weight loss, peak HMPV titer, or time required for viral clearance. In addition, NK cell depletion does not affect the adaptive T cell response to HMPV infection. Thus, despite the importance of NK cells during the immune response against infections by many other viruses, these cells are expendable during HMPV infection, at least in a mouse model.

Additionally, I show that a non-replicating VLP vaccine fully protects wild-type C57BL/6 mice from HMPV viral challenge in the lungs for at least six months post-vaccination. Vaccination alone elicited TCD8 that recognized specific epitopes in each of the two HMPV proteins incorporated into the VLPs. Lung TCD8 responding to non-replicating VLPs expressed lower levels of the inhibitory receptors PD-1 and TIM-3 than those responding to replicating virus; however, inhibitory receptor expression on spleen TCD8 was much lower than that of lung TCD8 in all groups of mice. Viral challenge after vaccination abrogated the low-inhibitory receptor expression phenotype of TCD8 in vaccinated mice prior to challenge. These results have important implications for design of novel therapeutics and vaccine strategies against respiratory viruses.

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