TY - JOUR
T1 - P22-Based Nanovaccines against Enterohemorrhagic Escherichia coli
AU - Huerta-Saquero, Alejandro
AU - Chapartegui Gonzalez, Itziar
AU - Bowser, Sarah
AU - Khakhum, Nittaya
AU - Stockton, Jacob L.
AU - Torres, Alfredo G.
N1 - Publisher Copyright:
© 2023 American Society for Microbiology. All rights reserved.
PY - 2023/3
Y1 - 2023/3
N2 - Enterohemorrhagic Escherichia coli (EHEC) is an important causative agent of diarrhea in humans that causes outbreaks worldwide. Efforts have been made to mitigate the morbidity and mortality caused by these microorganisms; however, the global incidence is still high, causing hundreds of deaths per year. Several vaccine candidates have been evaluated that demonstrate some stability and therapeutic potential but have limited overarching effect. Virus-like particles have been used successfully as nanocontainers for the targeted delivery of drugs, proteins, or nucleic acids. In this study, phage P22 nanocontainers were used as a carrier for the highly antigenic T3SS structural protein EscC that is conserved between EHEC and other enteropathogenic bacteria. We were able to stably incorporate the EscC protein into P22 nanocontainers. The EscC-P22 particles were used to intranasally inoculate mice, which generated specific antibodies against EscC. These antibodies increased the phagocytic activity of murine macrophages infected with EHEC in vitro and reduced bacterial adherence to Caco-2 epithelial cells in vitro, illustrating their functionality. The EscC-P22-based particles are a potential nanovaccine candidate for immunization against EHEC O157:H7 infections. IMPORTANCE This study describes the initial attempt to use P22 viral-like particles as nanocontainers expressing enterohemorrhagic Escherichia coli (EHEC) proteins that are immunogenic and could be used as effective vaccines against EHEC infections.
AB - Enterohemorrhagic Escherichia coli (EHEC) is an important causative agent of diarrhea in humans that causes outbreaks worldwide. Efforts have been made to mitigate the morbidity and mortality caused by these microorganisms; however, the global incidence is still high, causing hundreds of deaths per year. Several vaccine candidates have been evaluated that demonstrate some stability and therapeutic potential but have limited overarching effect. Virus-like particles have been used successfully as nanocontainers for the targeted delivery of drugs, proteins, or nucleic acids. In this study, phage P22 nanocontainers were used as a carrier for the highly antigenic T3SS structural protein EscC that is conserved between EHEC and other enteropathogenic bacteria. We were able to stably incorporate the EscC protein into P22 nanocontainers. The EscC-P22 particles were used to intranasally inoculate mice, which generated specific antibodies against EscC. These antibodies increased the phagocytic activity of murine macrophages infected with EHEC in vitro and reduced bacterial adherence to Caco-2 epithelial cells in vitro, illustrating their functionality. The EscC-P22-based particles are a potential nanovaccine candidate for immunization against EHEC O157:H7 infections. IMPORTANCE This study describes the initial attempt to use P22 viral-like particles as nanocontainers expressing enterohemorrhagic Escherichia coli (EHEC) proteins that are immunogenic and could be used as effective vaccines against EHEC infections.
KW - EHEC
KW - P22-based nanovaccines
KW - nanocontainer
KW - pathogenic Escherichia coli
UR - http://www.scopus.com/inward/record.url?scp=85154063187&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85154063187&partnerID=8YFLogxK
U2 - 10.1128/spectrum.04734-22
DO - 10.1128/spectrum.04734-22
M3 - Article
C2 - 36943089
AN - SCOPUS:85154063187
SN - 2165-0497
VL - 11
JO - Microbiology Spectrum
JF - Microbiology Spectrum
IS - 2
ER -