Shigella sonnei vaccine candidates WRSs2 and WRSs3 are as immunogenic as WRSS1, a clinically tested vaccine candidate, in a primate model of infection

• Published in: Vaccine Vol. 29; no. 37; pp. 6371 - 6378
• Main Authors: Barnoy, S, Baqar, S, Kaminski, R.W, Collins, T, Nemelka, K, Hale, T.L, Ranallo, R.T, Venkatesan, M.M
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 26.08.2011; Elsevier; Elsevier Limited
• Subjects: Allergy and Immunology; Animal models; Animals; Antibodies, Bacterial - blood; Antigens, Bacterial - immunology; Applied microbiology; Bacteria; bacterial antigens; Bacterial Proteins - genetics; Bacterial Proteins - immunology; Bacteriology; Biological and medical sciences; Candidates; Cell culture; clinical trials; Colonization; Dysentery; Dysentery, Bacillary - immunology; Dysentery, Bacillary - prevention & control; epithelium; excretion; Feces - cytology; Fever; Food contamination; Fundamental and applied biological sciences. Psychology; gastrointestinal system; genes; humans; Immune response; Immunogenicity; Immunoglobulin A - blood; Immunoglobulin G - blood; Live vaccine candidates; live vaccines; Macaca mulatta; Macaca mulatta - immunology; Macaca mulatta - virology; Microbiology; Miscellaneous; mucosal immunity; Proteins; Shigella; Shigella sonnei; Shigella sonnei - immunology; Shigella Vaccines - administration & dosage; Shigella Vaccines - adverse effects; Shigella Vaccines - immunology; Shigellosis; Studies; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Attenuated - administration & dosage; Vaccines, Attenuated - adverse effects; Vaccines, Attenuated - genetics; Vaccines, Attenuated - immunology; Vaccines, Synthetic - genetics; Vaccines, Synthetic - immunology; volunteers; Waterborne diseases; WRSs2; WRSs3; United States > US; WRSs3; Shigella sonnei; Live vaccine candidates; WRSs2; Vertebrata; Mammalia; Immunogenicity; Primates; Bacteria; Models; Vaccine; Enterobacteriaceae
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2011.04.115

Shigella causes diarrhea and dysentery through contaminated food and water. Shigella sonnei live vaccine candidates WRSs2 and WRSs3 are attenuated principally by the loss of VirG(IcsA) that prevents bacterial spread within the colonic epithelium. In this respect they are similar to the clinically tested vaccine candidate WRSS1. However, WRSs2 and WRSs3 are further attenuated by loss of senA, senB and WRSs3 also lacks msbB2. As previously shown in cell culture assays and in small animal models, these additional gene deletions reduced the levels of enterotoxicity and endotoxicity of WRSs2 and WRSs3, potentially making them safer than WRSS1. However the behavior of these second-generation VirG(IcsA)-based vaccine candidates in eliciting an immune response in a gastrointestinal model of infection has not been evaluated. In this study, WRSs2 and WRSs3 were nasogastrically administered to rhesus monkeys that were evaluated for colonization, as well as for systemic and mucosal immune responses. Both vaccine candidates were safe in rhesus monkeys and behaved comparably to WRSS1 in bacterial excretion rates that demonstrated robust intestinal colonization. Furthermore, humoral and mucosal immune responses elicited against bacterial antigens appeared similar in all categories across all three strains indicating that the additional gene deletions did not compromise the immunogenicity of these vaccine candidates. Based on data from previous clinical trials with WRSS1, it is likely that, WRSs2 and WRSs3 will not only be safer in human volunteers but will generate comparable levels of systemic and mucosal immune responses that were achieved with WRSS1.