Development Of A Live, Oral, Attenuated Vaccine Against El Tor Cholera

• Published in: The Journal of infectious diseases Vol. 170; no. 6; pp. 1518 - 1523
• Main Authors: Taylor, David N., Killeen, Kevin P., Hack, Dallas C., Kenner, Julie R., Coster, Trinka S., Beattie, David T., Ezzell, John, Hyman, Tracy, Trofa, Andrew, Sjogren, Maria H., Friedlander, Arthur, Mekalanos, John J., Sadoff, Jerald C.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.12.1994; University of Chicago Press
• Subjects: Adolescent; Adult; Animals; Animals, Suckling; Antibodies, Bacterial - blood; Bacterial diseases; Biological and medical sciences; Cholera; Cholera - prevention & control; Cholera vaccine; Cholera Vaccines - adverse effects; Cholera Vaccines - genetics; Cholera Vaccines - immunology; Diarrhea; Dosage; Feces - microbiology; Female; Genes, Bacterial - genetics; Human bacterial diseases; Humans; Immunoglobulin G - blood; Infectious diseases; Intestines - microbiology; Major Articles; Male; Medical sciences; Mice; Microbial colonization; Recombination, Genetic; Sequence Deletion; Toxins; Transcriptional regulatory elements; Tropical bacterial diseases; Vaccination; Vaccines, Attenuated - adverse effects; Vaccines, Attenuated - genetics; Vaccines, Attenuated - immunology; Vibrio cholerae; Vibrio cholerae - genetics; Vibrio cholerae - growth & development; Vibrio cholerae - immunology; Vibrio cholerae - pathogenicity; Virulence; Volunteerism; Human; Immune response; Vaccine strain; Toxicity; Oral administration; Vaccine; Infection; Prevention; Immunoprophylaxis; Production; Bacteriosis; Bacteria; Vibrionaceae; Cholera; Attenuated strain; Vibrio cholerae elTor
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/170.6.1518

Vibrio cholerae EI Tor strains from Peru, Bangladesh, and Bahrain were attenuated by deletion of a genetic element that encodes virulence factors and RSI. The B subunit of ctx (ctxB) was reintroduced into the recA gene of the deletion mutants, rendering them unable to recombine with exogenous genetic elements and generating Peru-3, Bang-3, and Bah-3. Fifteen volunteers received one dose of various vaccine strains at 4 ‘d7 106 to 1 ’d7 108 cfu. All strains colonized the gut. A ⩽5? 4-fold rise in vibriocidal titer was observed in 14 volunteers, with titers of ⩽5? 1600 in 13. Peru-3 was the least reactogenic, but 2 of 6 volunteers had loose stools. Peru-14, a filamentous motility-deficient mutant of Peru-J, was well tolerated and colonized 18 of 21 volunteers at doses of 2 ‘d7 106 to 1 ’d7 109 cfu. Also, when 8 Peru-3 or Peru-S vaccinees, 5 Peru-14 vaccinees, and 8 controls were challenged with 2 'd7 106 cfu V. cholerae EI Tor Inaba (NI6961), 11 vaccinees were protected compared with no controls. Peru-14 shows promise as a safe, effective, single-dose oral vaccine against EI Tor cholera.