TY - JOUR
T1 - Evaluation of a live attenuated s. Sonnei vaccine strain in the human enteroid model
AU - Pilla, Giulia
AU - Wu, Tao
AU - Grassel, Christen
AU - Moon, Jonathan
AU - Foulke-Abel, Jennifer
AU - Tang, Christoph M.
AU - Barry, Eileen M.
N1 - Funding Information:
This research was funded by NIH NIAID P01 AI125181, NIH NIAID U19AI109776 awarded to E.M.B., Wellcome Trust Senior Investigator awarded to C.M.T. (G102908) and Oxford-MRC Doctoral Training Partnership supplementary funding awarded to G.P. The confocal microscope was purchased with an NIH shared instrumentation grant (S10 OD025244). The Johns Hopkins GI Core Center that manages the microscope is funded by NIH P30 DK089502.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/8
Y1 - 2021/8
N2 - Shigella is a leading cause of bacillary dysentery worldwide, responsible for high death rates especially among children under five in low–middle income countries. Shigella sonnei prevails in high-income countries and is becoming prevalent in industrializing countries, where multi-drug resistant strains have emerged, as a significant public health concern. One strategy to combat drug resistance in S. sonnei is the development of effective vaccines. There is no licensed vaccine against Shigella, and development has been hindered by the lack of an effective small-animal model. In this work, we used human enteroids, for the first time, as a model system to evaluate a plasmid-stabilized S. sonnei live attenuated vaccine strain, CVD 1233-SP, and a multivalent derivative, CVD 1233-SP::CS2-CS3, which expresses antigens from enterotoxigenic Escherichia coli. The strains were also tested for immunogenicity and protective capacity in the guinea pig model, demonstrating their ability to elicit serum and mucosal antibody responses as well as protection against challenge with wild-type S. sonnei. These promising results highlight the utility of enteroids as an innovative pre-clinical model to evaluate Shigella vaccine candidates, constituting a significant advance for the development of preventative strategies against this important human pathogen.
AB - Shigella is a leading cause of bacillary dysentery worldwide, responsible for high death rates especially among children under five in low–middle income countries. Shigella sonnei prevails in high-income countries and is becoming prevalent in industrializing countries, where multi-drug resistant strains have emerged, as a significant public health concern. One strategy to combat drug resistance in S. sonnei is the development of effective vaccines. There is no licensed vaccine against Shigella, and development has been hindered by the lack of an effective small-animal model. In this work, we used human enteroids, for the first time, as a model system to evaluate a plasmid-stabilized S. sonnei live attenuated vaccine strain, CVD 1233-SP, and a multivalent derivative, CVD 1233-SP::CS2-CS3, which expresses antigens from enterotoxigenic Escherichia coli. The strains were also tested for immunogenicity and protective capacity in the guinea pig model, demonstrating their ability to elicit serum and mucosal antibody responses as well as protection against challenge with wild-type S. sonnei. These promising results highlight the utility of enteroids as an innovative pre-clinical model to evaluate Shigella vaccine candidates, constituting a significant advance for the development of preventative strategies against this important human pathogen.
KW - Human enteroids
KW - Shigella sonnei
KW - Shigella vaccine
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U2 - 10.3390/pathogens10091079
DO - 10.3390/pathogens10091079
M3 - Article
C2 - 34578112
AN - SCOPUS:85114050515
SN - 2076-0817
VL - 10
JO - Pathogens
JF - Pathogens
IS - 9
M1 - 1079
ER -