Safety and immunogenicity of WRSd1, a live attenuated Shigella dysenteriae type 1 vaccine candidate

Robin McKenzie; Malabi M. Venkatesan; Marcia K. Wolf; Dilara Islam; Shannon Grahek; Andrea M. Jones; Arlene Bloom; David N. Taylor; Thomas L. Hale; A. Louis Bourgeois

doi:10.1016/j.vaccine.2008.03.079

Safety and immunogenicity of WRSd1, a live attenuated Shigella dysenteriae type 1 vaccine candidate

Robin McKenzie, Malabi M. Venkatesan, Marcia K. Wolf, Dilara Islam, Shannon Grahek, Andrea M. Jones, Arlene Bloom, David N. Taylor, Thomas L. Hale, A. Louis Bourgeois

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

Among Shigella serotypes Shigella dysenteriae type 1 produces the most severe disease, including cases of hemolytic-uremic syndrome and pandemic outbreaks. WRSd1 is a live S. dysenteriae 1 strain attenuated by deletion of the virG(icsA) gene, which encodes a protein that mediates intercellular spread, and stxA and stxB, which encode the Shiga toxin. In this Phase I trial five groups of eight subjects ingested escalating doses of WRSd1 ranging from 10³ to 10⁷ CFU. No subject experienced fever or shigellosis, but 20% had diarrhea. Approximately two-thirds of subjects developed an IgA-ASC response to LPS. Days of fecal shedding of the vaccine strain, but not dose ingested, correlated with stronger immune responses. These results suggest that to be effective an attenuated Shigella vaccine must colonize well.

Original language	English (US)
Pages (from-to)	3291-3296
Number of pages	6
Journal	Vaccine
Volume	26
Issue number	26
DOIs	https://doi.org/10.1016/j.vaccine.2008.03.079
State	Published - Jun 19 2008
Externally published	Yes

Keywords

Live attenuated vaccine
S. dysenteriae
Shigella

ASJC Scopus subject areas

Molecular Medicine
General Immunology and Microbiology
General Veterinary
Public Health, Environmental and Occupational Health
Infectious Diseases

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10.1016/j.vaccine.2008.03.079

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title = "Safety and immunogenicity of WRSd1, a live attenuated Shigella dysenteriae type 1 vaccine candidate",

abstract = "Among Shigella serotypes Shigella dysenteriae type 1 produces the most severe disease, including cases of hemolytic-uremic syndrome and pandemic outbreaks. WRSd1 is a live S. dysenteriae 1 strain attenuated by deletion of the virG(icsA) gene, which encodes a protein that mediates intercellular spread, and stxA and stxB, which encode the Shiga toxin. In this Phase I trial five groups of eight subjects ingested escalating doses of WRSd1 ranging from 103 to 107 CFU. No subject experienced fever or shigellosis, but 20% had diarrhea. Approximately two-thirds of subjects developed an IgA-ASC response to LPS. Days of fecal shedding of the vaccine strain, but not dose ingested, correlated with stronger immune responses. These results suggest that to be effective an attenuated Shigella vaccine must colonize well.",

keywords = "Live attenuated vaccine, S. dysenteriae, Shigella",

author = "Robin McKenzie and Venkatesan, {Malabi M.} and Wolf, {Marcia K.} and Dilara Islam and Shannon Grahek and Jones, {Andrea M.} and Arlene Bloom and Taylor, {David N.} and Hale, {Thomas L.} and Bourgeois, {A. Louis}",

note = "Funding Information: This work was supported by the U.S. Army Military Infectious Disease Research Program, U.S. Army grant # DAMD17-01-D-0011 and Johns Hopkins University School of Medicine General Clinical Research Center grant # M01-RR00052 from the National Center for Research Resources, NIH. The material presented in this article has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation or publication. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting true views of the WRAIR/NMRC, the Department of the Army or the Department of Defense. ",

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AU - Venkatesan, Malabi M.

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AU - Islam, Dilara

AU - Grahek, Shannon

AU - Jones, Andrea M.

AU - Bloom, Arlene

AU - Taylor, David N.

AU - Hale, Thomas L.

AU - Bourgeois, A. Louis

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PY - 2008/6/19

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N2 - Among Shigella serotypes Shigella dysenteriae type 1 produces the most severe disease, including cases of hemolytic-uremic syndrome and pandemic outbreaks. WRSd1 is a live S. dysenteriae 1 strain attenuated by deletion of the virG(icsA) gene, which encodes a protein that mediates intercellular spread, and stxA and stxB, which encode the Shiga toxin. In this Phase I trial five groups of eight subjects ingested escalating doses of WRSd1 ranging from 103 to 107 CFU. No subject experienced fever or shigellosis, but 20% had diarrhea. Approximately two-thirds of subjects developed an IgA-ASC response to LPS. Days of fecal shedding of the vaccine strain, but not dose ingested, correlated with stronger immune responses. These results suggest that to be effective an attenuated Shigella vaccine must colonize well.

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Safety and immunogenicity of WRSd1, a live attenuated Shigella dysenteriae type 1 vaccine candidate

Abstract

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