title: Phase I evaluation of delta virG Shigella sonnei live, attenuated, oral vaccine strain WRSS1 in healthy adults.
abstract: We conducted a phase I trial with healthy adults to evaluate WRSS1, a live, oral Delta virG Shigella sonnei vaccine candidate. In a double-blind, randomized, dose-escalating fashion, inpatient volunteers received a single dose of either placebo (n = 7) or vaccine (n = 27) at 3 x 10(3) CFU (group 1), 3 x 10(4) CFU (group 2), 3 x 10(5) CFU (group 3), or 3 x 10(6) CFU (group 4). The vaccine was generally well tolerated, although a low-grade fever or mild diarrhea occurred in six (22%) of the vaccine recipients. WRSS1 was recovered from the stools of 50 to 100% of the vaccinees in each group. The geometric mean peak anti-lipopolysaccharide responses in groups 1 to 4, respectively, were 99, 39, 278, and 233 for immunoglobulin (IgA) antibody-secreting cell counts; 401, 201, 533, and 284 for serum reciprocal IgG titers; and 25, 3, 489, and 1,092 for fecal IgA reciprocal titers. Postvaccination increases in gamma interferon production in response to Shigella antigens occurred in some volunteers. We conclude that WRSS1 vaccine is remarkably immunogenic in doses ranging from 10(3) to 10(6) CFU but elicits clinical reactions that must be assessed in further volunteer trials.
authors.affiliation: Division of Infectious Disease and Tropical Pediatrics, Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. kkotloff@medicine.umaryland.edu
authors.forename: Karen L
authors.initials: KL
authors.lastname: Kotloff
authors.forename: David N
authors.initials: DN
authors.lastname: Taylor
authors.forename: Marcelo B
authors.initials: MB
authors.lastname: Sztein
authors.forename: Steven S
authors.initials: SS
authors.lastname: Wasserman
authors.forename: Genevieve A
authors.initials: GA
authors.lastname: Losonsky
authors.forename: James P
authors.initials: JP
authors.lastname: Nataro
authors.forename: Malabi
authors.initials: M
authors.lastname: Venkatesan
authors.forename: Antoinette
authors.initials: A
authors.lastname: Hartman
authors.forename: William D
authors.initials: WD
authors.lastname: Picking
authors.forename: David E
authors.initials: DE
authors.lastname: Katz
authors.forename: James D
authors.initials: JD
authors.lastname: Campbell
authors.forename: Myron M
authors.initials: MM
authors.lastname: Levine
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Hale
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D004311:Double-Blind Method; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D007781:Lactoferrin / Q000032:analysis; D008070:Lipopolysaccharides / Q000276:immunology; D008875:Middle Aged; D022281:Shigella Vaccines / Q000276:immunology*; D012764:Shigella sonnei / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D007070:Immunoglobulin A; D008070:Lipopolysaccharides; D022281:Shigella Vaccines; D014613:Vaccines, Attenuated; D007371:Interferon-gamma; D007781:Lactoferrin