Authors: Lisa Bedford, Suramya Fonseka, Tara Boren, Ryan T. Ranallo, Akamol E. Suvarnapunya, James E. Lee, Shoshana Barnoy and Malabi M. Venkatesan

Lisa Bedford

Division of Bacterial & Rickettsial Diseases, Walter Reed Army Institute of Research, Silver Spring, MD

Suramya Fonseka

Division of Bacterial & Rickettsial Diseases, Walter Reed Army Institute of Research, Silver Spring, MD

Tara Boren

Division of Bacterial & Rickettsial Diseases, Walter Reed Army Institute of Research, Silver Spring, MD

Ryan T. Ranallo

Division of Bacterial & Rickettsial Diseases, Walter Reed Army Institute of Research, Silver Spring, MD

Akamol E. Suvarnapunya

Division of Bacterial & Rickettsial Diseases, Walter Reed Army Institute of Research, Silver Spring, MD

James E. Lee

Division of Bacterial & Rickettsial Diseases, Walter Reed Army Institute of Research, Silver Spring, MD

Shoshana Barnoy

Division of Bacterial & Rickettsial Diseases, Walter Reed Army Institute of Research, Silver Spring, MD

Malabi M. Venkatesan

Corresponding author: malabi.venkatesan@US.ARMY.MIL
Division of Bacterial & Rickettsial Diseases, Walter Reed Army Institute of Research, Silver Spring, MD

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Abstract:

Shigella sonnei live vaccine candidates WRSs2 and WRSs3 are principally attenuated by the loss of the virG(icsA) gene that prevents bacterial spread. In addition both strains lack enterotoxin SenA and a paralog SenB. WRSs3 also has a deletion in the gene encoding MsbB2. Both of these vaccine candidates are expected to be improved safer versions of WRSS1 that only lacked the virG(icsA) gene and was reactogenic in volunteer trials. During the construction of WRSs2 and WRSs3, segments of the virulence plasmid spanning two FRT sites were found to be inverted in orientation. These inversions have been analysed to show that the overall composition of the plasmid is unaltered. Furthermore, characterization of WRSs2 and WRSs3 in a cell culture and in an animal model have conclusively demonstrated that the segment inversions per se do not adversely affect the behavior of these vaccine candidates and pose no increased safety risk for human evaluation.

Article Addendum to:
Houten NE van, KA Henry, GP Smith, JK Scott. Engineering filamentous phage carriers to improve focusing of antibody responses against peptides. Vaccine 2010; 28: 2174-85
PMID: 19932216 DOI: 10.1016/j.vaccine.20