Development Of A Live, Oral, Attenuated Vaccine Against El Tor Cholera
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 geneti...
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| Published in | The Journal of infectious diseases Vol. 170; no. 6; pp. 1518 - 1523 |
|---|---|
| Main Authors | , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Chicago, IL
The University of Chicago Press
01.12.1994
University of Chicago Press |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0022-1899 1537-6613 |
| DOI | 10.1093/infdis/170.6.1518 |
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| Abstract | 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. |
|---|---|
| AbstractList | Vibrio cholerae El Tor strains from Peru, Bangladesh, and Bahrain were attenuated by deletion of a genetic element that encodes virulence factors and RS1. 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 x 10(6) to 1 x 10(8) cfu. All strains colonized the gut. A > or = 4-fold rise in vibriocidal titer was observed in 14 volunteers, with titers of > or = 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-3, was well tolerated and colonized 18 of 21 volunteers at doses of 2 x 10(6) to 1 x 10(9) cfu. Also, when 8 Peru-3 or Peru-5 vaccinees, 5 Peru-14 vaccinees, and 8 controls were challenged with 2 x 10(6) cfu V. cholerae El Tor Inaba (N16961), 11 vaccinees were protected compared with no controls. Peru-14 shows promise as a safe, effective, single-dose oral vaccine against El Tor cholera.Vibrio cholerae El Tor strains from Peru, Bangladesh, and Bahrain were attenuated by deletion of a genetic element that encodes virulence factors and RS1. 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 x 10(6) to 1 x 10(8) cfu. All strains colonized the gut. A > or = 4-fold rise in vibriocidal titer was observed in 14 volunteers, with titers of > or = 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-3, was well tolerated and colonized 18 of 21 volunteers at doses of 2 x 10(6) to 1 x 10(9) cfu. Also, when 8 Peru-3 or Peru-5 vaccinees, 5 Peru-14 vaccinees, and 8 controls were challenged with 2 x 10(6) cfu V. cholerae El Tor Inaba (N16961), 11 vaccinees were protected compared with no controls. Peru-14 shows promise as a safe, effective, single-dose oral vaccine against El Tor cholera. Vibrio cholerae El Tor strains from Peru, Bangladesh, and Bahrain were attenuated by deletion of a genetic element that encodes virulence factors and RS1. 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 x 10(6) to 1 x 10(8) cfu. All strains colonized the gut. A > or = 4-fold rise in vibriocidal titer was observed in 14 volunteers, with titers of > or = 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-3, was well tolerated and colonized 18 of 21 volunteers at doses of 2 x 10(6) to 1 x 10(9) cfu. Also, when 8 Peru-3 or Peru-5 vaccinees, 5 Peru-14 vaccinees, and 8 controls were challenged with 2 x 10(6) cfu V. cholerae El Tor Inaba (N16961), 11 vaccinees were protected compared with no controls. Peru-14 shows promise as a safe, effective, single-dose oral vaccine against El Tor cholera. 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. Vibrio cholerae El 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 X 10⁶ to 1 X 10⁸ cfu. All strains colonized the gut. A ⩾4-fold rise in vibriocidal titer was observed in 14 volunteers, with titers of ⩾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-3, was well tolerated and colonized 18 of 21 volunteers at doses of 2 X 10⁶ to 1 X 10⁹ cfu. Also, when 8 Peru-3 or Peru-5 vaccinees, 5 Peru-14 vaccinees, and 8 controls were challenged with 2 X 10⁶ cfu V. cholerae El Tor Inaba (N16961), 11 vaccinees were protected compared with no controls. Peru-14 shows promise as a safe, effective, single-dose oral vaccine against El Tor cholera. Vibrio cholerae El Tor strains from Peru, Bangladesh, and Bahrain were attenuated by deletion of a genetic element that encodes virulence factors and RS1. 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 x 10 super(6) to 1 x 10 super(8) cfu. All strains colonized the gut. A greater than or equal to 4-fold rise in vibriocidal titer was observed in 14 volunteers, with titers of greater than or equal to 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-3, was well tolerated and colonized 18 of 21 volunteers at doses of 2 x 10 super(6) to 1 x 10 super(9) cfu. Also, when 8 Peru-3 or Peru-5 vaccinees, 5 Peru-14 vaccinees, and 8 controls were challenged with 2 x 10 super(6) cfu V. cholerae El Tor Inaba (N16961), 11 vaccinees were protected compared with no controls. Peru-14 shows promise as a safe, effective, single-dose oral vaccine against El Tor cholera. |
| Author | Sadoff, Jerald C. Ezzell, John Taylor, David N. Coster, Trinka S. Kenner, Julie R. Mekalanos, John J. Beattie, David T. Killeen, Kevin P. Hack, Dallas C. Friedlander, Arthur Hyman, Tracy Trofa, Andrew Sjogren, Maria H. |
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| Copyright | Copyright 1994 The University of Chicago 1995 INIST-CNRS |
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| Issue | 6 |
| Keywords | Human Immune response Vaccine strain Toxicity Oral administration Vaccine Infection Prevention Immunoprophylaxis Production Bacteriosis Bacteria Vibrionaceae Cholera Attenuated strain Vibrio cholerae elTor |
| Language | English |
| License | CC BY 4.0 |
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| Notes | istex:4F69B25222364FFB47AAEFAABF02ED75506EB4E9 ark:/67375/HXZ-XZQ04G82-G Reprints or correspondence (present address): Dr. David N. Taylor, Naval Medical Research Institute Detachment, Unit 3800, APO AA 34031; from outside United States: NAMRID, Centro Medico Naval, Avenida Venezuela Cdra 36/s/n, Callao, Peru. Present affiliation: Department of Gastroenterology, Waiter Reed Army Medical Center, Washington, DC. ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Undefined-3 |
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| Snippet | 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... Vibrio cholerae El Tor strains from Peru, Bangladesh, and Bahrain were attenuated by deletion of a genetic element that encodes virulence factors and RSI. The... Vibrio cholerae El Tor strains from Peru, Bangladesh, and Bahrain were attenuated by deletion of a genetic element that encodes virulence factors and RS1. The... |
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| SubjectTerms | 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 |
| Title | Development Of A Live, Oral, Attenuated Vaccine Against El Tor Cholera |
| URI | https://api.istex.fr/ark:/67375/HXZ-XZQ04G82-G/fulltext.pdf https://www.jstor.org/stable/30133665 https://www.ncbi.nlm.nih.gov/pubmed/7995992 https://www.proquest.com/docview/16812277 https://www.proquest.com/docview/76885999 |
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