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Development of a psoralen + UVA light-inactivated whole cell vaccine for urinary tract infection caused by uropathogenic E. coli (UPEC)

Electronic Theses and Dissertations

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abstract
Uropathogenic E. coli (UPEC) contribute to a large proportion of urinary tract infections (UTI), which cause a significant economic and health burden in the U.S. every year. There is currently no vaccine licensed for use in the U.S. to prevent UTI. This study proposes a whole cell vaccine inactivated by psoralen + UVA light (PUVA), which targets nucleic acids. The hypothesis on which this work is based is that PUVA will preserve surface proteins, resulting in a more immunogenic vaccine relative to formalin inactivation which is known to damage protein antigenicity. The work presented demonstrates that the PUVA method reproducibly inactivated UPEC. The properties of PUVA-UPEC were studied in comparison to formalin-inactivated UPEC. PUVA-UPEC were “killed but metabolically active (KBMA),” while formalin-UPEC were not. After PUVA treatment, surface adhesins including Type I pili and P fimbriae retained the capacity to mediate binding to yeast mannosylated proteins and human red blood cells, respectively, while formalin treatment reduced adhesive activity in both assays. The data supports PUVA-UPEC as an alternative inactivated vaccine candidate due to preservation of the bacterial surface in a native form and retention of metabolic activity, both properties that may enhance immunogenicity relative to formalin-inactivated bacteria.
subject
fimbriae
inactivation
KBMA
psoralen
UPEC
UTI
contributor
Morse, Alexis Elizabeth (author)
Westcott, Marlena M (committee chair)
Zafar, Ammar (committee member)
Sanders, John W (committee member)
date
2022-01-15T09:35:32Z (accessioned)
2022 (issued)
degree
Biomedical Science – MS (discipline)
2023-01-14 (liftdate)
embargo
2023-01-14 (terms)
identifier
http://hdl.handle.net/10339/99391 (uri)
language
en (iso)
publisher
Wake Forest University
title
Development of a psoralen + UVA light-inactivated whole cell vaccine for urinary tract infection caused by uropathogenic E. coli (UPEC)
type
Thesis

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