Item Details

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)

2023-07-14T08:30:05Z (available)

2022 (issued)

degree

Biomedical Science – MS (discipline)

embargo

2023-07-14 (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