Lack of immune response to the Vi component of a Vi-positive variant of the Salmonella typhi live oral vaccine strain Ty21a in human studies.
New typhoid vaccines have been sought to replace the reactogenic parenteral whole cell vaccines. Both Ty21a, a live oral attenuated Vi-negative Salmonella typhi vaccine strain, and parenteral Vi polysaccharide vaccine are safe and efficacious in field trials. To achieve potentially greater protective efficacy, a derivative of Ty21a that expresses Vi polysaccharide was prepared and its safety and immunogenicity assessed in 27 adult volunteers. The volunteers received either one dose of 5 x 10(5), 5 x 10(7), or 5 x 10(9) cfu or three doses of 5 x 10(9) cfu of lyophilized vaccine and were observed for adverse effects on a research isolation ward. The vaccine was well tolerated; however, at the highest dose, 13% of volunteers had mild diarrhea. Serial blood cultures were negative for the vaccine strain. Vaccine was shed in the stool of most volunteers at the higher doses for 1-4 days. No serum antibodies to Vi, circulating cells secreting antibody to Vi, or jejunal fluid antibodies to Vi were detected in any volunteer.
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Department of Medicine, University of Maryland School of Medicine, Baltimore 21201.
Losonsky
G
G
Taylor
D N
DN
Baron
L S
LS
Kopecko
D
D
Cryz
S
S
Levine
M M
MM
D000328:Adult; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D000942:Antigens, Bacterial / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D011135:Polysaccharides, Bacterial / Q000276:immunology; D012485:Salmonella typhi / Q000276:immunology*; D014436:Typhoid-Paratyphoid Vaccines / Q000009:adverse effects / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000276:immunology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011135:Polysaccharides, Bacterial; D014436:Typhoid-Paratyphoid Vaccines; D014613:Vaccines, Attenuated