Phase I evaluation of delta virG Shigella sonnei live, attenuated, oral vaccine strain WRSS1 in healthy adults.
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.
Kotloff
Karen L
KL
Division of Infectious Disease and Tropical Pediatrics, Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. kkotloff@medicine.umaryland.edu
Taylor
David N
DN
Sztein
Marcelo B
MB
Wasserman
Steven S
SS
Losonsky
Genevieve A
GA
Nataro
James P
JP
Venkatesan
Malabi
M
Hartman
Antoinette
A
Picking
William D
WD
Katz
David E
DE
Campbell
James D
JD
Levine
Myron M
MM
Hale
Thomas L
TL
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
D000907:Antibodies, Bacterial; D007070:Immunoglobulin A; D008070:Lipopolysaccharides; D022281:Shigella Vaccines; D014613:Vaccines, Attenuated; D007371:Interferon-gamma; D007781:Lactoferrin