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Research Paper

Safety and Immunogenicity of CVD 1208S, a Live, Oral ΔguaBA Δsen Δset Shigella flexneri 2a Vaccine Grown on Animal-Free Media

Karen L. Kotloff, Jakub K. Simon, Marcela Pasetti, Marcelo B. Sztein, Stacey L. Wooden, Sofie Livio, James P. Nataro, William C. Blackwelder, Eileen M. Barry, Wendy Picking and Myron M. Levine

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A previous Phase 1 trial demonstrated that Shigella flexneri 2a deleted in guaBA, sen and set (strain CVD 1208) is well-tolerated and immunogenic after a single oral dose of 108 or 109 CFU. To facilitate further clinical development, the strain was reconstructed using animal-free media to conform to regulatory guidelines, and designated CVD1208S. Healthy inpatient volunteers were randomized (double-blind) to receive a single oral dose of either CVD 1208S (108 [n = 7] or 109 [n = 7] CFU) or placebo (n = 2). Both vaccine dosage levels were generally well-tolerated. Anti-lipopolysaccharide responses, measured as IgA antibody secreting cells, serum IgG, or fecal IgA levels, occurred in 7 (100%), 3 (43%) and 2 (29%) subjects, respectively, following inoculation with 109 CFU. Interferon gamma production in response to Shigella antigens was observed in 1 of 4 (25%) and 4 of 7 (57%) subjects, respectively, following inoculation with 108 and 109 CFU. We conclude that CVD 1208S retains a favorable safety and immunogenicity profile after reconstruction on animal-free media, comparable to that seen with CVD 1208, which was constructed on media containing animal products, and shows promise as a live, oral Shigella vaccine.

Authors

Karen L. Kotloff

University of Maryland School of Medicine, Center for Vaccine Development, Baltimore, Maryland USA

Jakub K. Simon

Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD USA

Marcela Pasetti

Department of Pediatrics, Department of Medicine, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland

Marcelo B. Sztein

Department of Pediatrics, Department of Medicine, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland

Stacey L. Wooden

Department of Pediatrics, Department of Medicine, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland

Sofie Livio

Divison of Geographic Medicine, Department of Medicine, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland

James P. Nataro

Department of Medicine, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland

William C. Blackwelder

Divison of Geographic Medicine, Department of Medicine, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland

Eileen M. Barry

Divison of Geographic Medicine, Department of Medicine, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland

Wendy Picking

Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas

Myron M. Levine

Center for Vaccine Development, University of Maryland School of Medicin; Baltimore, Maryland USA

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