Iron Receptor Antigen-Based Mucosal Immunization Prevents Urinary Tract Infection
DOI:
https://doi.org/10.59675/U125Keywords:
Urinary tract infection (UTI), Uropathogenic Escherichia coli (UPEC), UTI vaccine, Iron acquisition systems, Outer membrane iron receptors.Abstract
Urinary tract infection (UTI) is a leading bacterial infection worldwide caused by Uropathogenic Escherichia coli (UPEC). Despite the apparent ease of treatment, they carry an enormous health and economic burden because of the extent of relapses and resistance to anti-infective agents. This study aimed to develop a UTI vaccine that targets the iron acquisition systems of UPEC. With the help of functional vaccinology, six outer membrane iron receptors (ChuA, Hma, Iha, IreA, IroN, and IutA) were selected as possible vaccine candidates for further studies. Mouse models were immunised intranasally with recombinant antigens Hma, IreA, and IutA, mixing cholera toxin as an adjuvant. The humoral and cellular immune responses raised in vaccinated mice were highly robust. Immunisation conferred protection in specific locales, such as Hma to the kidney and IreA and IutA gave immunity to the bladder. This study is the first to describe specific immune protection against UPEC in a mouse model, as characterised by significant increases in antibody IgA in urine and IgG in serum, as well as the proinflammatory cytokines IL-17 and IFN-γ. This study provides proof of principle for iron acquisition pathways to be targets for vaccine development against UTIs. As iron is an essential nutrient for UPEC, vaccines directed at iron acquisition systems provide an excellent basis for future multivalent subunit vaccines that can alleviate the burden of UPEC infections.
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