TY - JOUR
T1 - Efficacy of EHEC gold nanoparticle vaccines evaluated with the Shiga toxin-producing Citrobacter rodentium mouse model
AU - Bowser, Sarah
AU - Melton-Celsa, Angela
AU - Chapartegui Gonzalez, Itziar
AU - Torres, Alfredo G.
N1 - Publisher Copyright:
Copyright © 2023 Bowser et al.
PY - 2024/1
Y1 - 2024/1
N2 - Enterohemorrhagic Escherichia coli (EHEC) is a group of pathogenic bacteria responsible for several foodborne-associated outbreaks of human diarrheal disease. Although EHEC is a major cause of morbidity as well as the condition known as hemolytic uremic syndrome, linked to the production of Shiga toxins (Stx), there are no licensed vaccines approved for human use. Fully assessing vaccine efficacy against EHEC infections is challenging because conventional adult mice are inherently resistant to EHEC infection and do not develop hallmark symptoms of the disease. Therefore, in this study, we utilized a strain of the murine pathogen Citrobacter rodentium that has been lysogenized to produce Stx2d, which consistently causes lethal infection and other measurable disease outcomes following oral challenge, to further evaluate the protective efficacy of our previously formulated EHEC gold nanoparticle (AuNP) vaccines. Using this model, along with a non-Stx2d-producing C. rodentium strain, we assessed the protection conferred by AuNPs conjugated to three EHEC antigens: EscC, LomW, and intimin (Eae). We demonstrated that intranasally immunizing mice with AuNP-Eae provides partial protection against mortality caused by Stx2d-producing C. rodentium and that AuNP-EscC and AuNP-Eae moderately reduce intestinal burden of the non-Stx2d-producing C. rodentium strain compared with adjuvant-only-treated mice. Additionally, the AuNP-protein vaccines induced antigen- and pathogen-specific serum IgG and fecal IgA against both EHEC and C. rodentium while in vitro functional assays indicate that the elicited antibodies are bactericidal and prevent adherence of C. rodentium to intestinal epithelial cells. We propose that C. rodentium murine data could translate into correlates of protection.
AB - Enterohemorrhagic Escherichia coli (EHEC) is a group of pathogenic bacteria responsible for several foodborne-associated outbreaks of human diarrheal disease. Although EHEC is a major cause of morbidity as well as the condition known as hemolytic uremic syndrome, linked to the production of Shiga toxins (Stx), there are no licensed vaccines approved for human use. Fully assessing vaccine efficacy against EHEC infections is challenging because conventional adult mice are inherently resistant to EHEC infection and do not develop hallmark symptoms of the disease. Therefore, in this study, we utilized a strain of the murine pathogen Citrobacter rodentium that has been lysogenized to produce Stx2d, which consistently causes lethal infection and other measurable disease outcomes following oral challenge, to further evaluate the protective efficacy of our previously formulated EHEC gold nanoparticle (AuNP) vaccines. Using this model, along with a non-Stx2d-producing C. rodentium strain, we assessed the protection conferred by AuNPs conjugated to three EHEC antigens: EscC, LomW, and intimin (Eae). We demonstrated that intranasally immunizing mice with AuNP-Eae provides partial protection against mortality caused by Stx2d-producing C. rodentium and that AuNP-EscC and AuNP-Eae moderately reduce intestinal burden of the non-Stx2d-producing C. rodentium strain compared with adjuvant-only-treated mice. Additionally, the AuNP-protein vaccines induced antigen- and pathogen-specific serum IgG and fecal IgA against both EHEC and C. rodentium while in vitro functional assays indicate that the elicited antibodies are bactericidal and prevent adherence of C. rodentium to intestinal epithelial cells. We propose that C. rodentium murine data could translate into correlates of protection.
KW - Citrobacter rodentium
KW - EHEC
KW - Shiga toxin
KW - hemolytic uremic syndrome
KW - nanovaccines
UR - http://www.scopus.com/inward/record.url?scp=85182500865&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85182500865&partnerID=8YFLogxK
U2 - 10.1128/spectrum.02261-23
DO - 10.1128/spectrum.02261-23
M3 - Article
C2 - 38047703
AN - SCOPUS:85182500865
SN - 2165-0497
VL - 12
JO - Microbiology Spectrum
JF - Microbiology Spectrum
IS - 1
ER -