Two live attenuated Shigella flexneri 2a strains WRSf2G12 and WRSf2G15: a new combination of gene deletions for 2nd generation live attenuated vaccine candidates.
Shigella infections are a major cause of inflammatory diarrhea and dysentery worldwide. First-generation virG-based live attenuated Shigella strains have been successfully tested in phase I and II clinical trials and are a leading approach for Shigella vaccine development. Additional gene deletions in senA, senB and msbB2 have been engineered into second-generation virG-based Shigella flexneri 2a strains producing WRSf2G12 and WRSf2G15. Both strains harbor a unique combination of gene deletions designed to increase the safety of live Shigella vaccines. WRSf2G12 and WRSf2G15 are genetically stable and highly attenuated in both cell culture and animal models of infection. Ocular immunization of guinea pigs with either strain induces robust systemic and mucosal immune responses that protect against homologous challenge with wild-type Shigella. The data support further evaluation of the second-generation strains in a phase I clinical trial.
Division of Bacterial & Rickettsial Diseases, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20814, United States.
Ryan T
RT
Ranallo
Suramya
S
Fonseka
Tara L
TL
Boren
Lisa A
LA
Bedford
Robert W
RW
Kaminski
Sejal
S
Thakkar
Malabi M
MM
Venkatesan
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004355:Drug Stability; D004405:Dysentery, Bacillary / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D017353:Gene Deletion; D005798:Genes, Bacterial; D006168:Guinea Pigs; D006367:HeLa Cells; D006801:Humans; D018928:Immunity, Mucosal; D007115:Immunization Schedule; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D022281:Shigella Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D012763:Shigella flexneri / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D022281:Shigella Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic