Construction and characterisation of O139 cholera vaccine candidates.
The hemagglutinin/protease (HA/P) seems to be an attractive locus for the insertion of heterologous tags in live cholera vaccine strains. A deltaCTXphi spontaneous mutant derived from a pathogenic strain of O139 Vibrio cholerae was sequentially manipulated to obtain hapA Colon, two colons celA derivatives which were later improved in their environmental safety by means of a thyA mutation. All the strains here obtained showed similar phenotypes in traits known to be remarkable for live cholera vaccines irrespective of their motility phenotypes, although the hapA mutants had a 10-fold decrease in their colonisation capacity compared with their parental strains in the infant mouse cholera model. However, the subsequent thyA mutation did not affect their colonisation properties in the same model. These preliminary results pave the way for further clinical assays to confirm the possibilities of these vaccine prototypes as safe and effective tools for the prevention of O139 cholera.
Ledón
Talena
T
Grupo de Genética, Centro Nacional de Investigaciones Científicas, AP 6412 Havana, Cuba. talena@biocnic.cneuro.edu.cu
Valle
Edgar
E
Valmaseda
Tania
T
Cedré
Barbara
B
Campos
Javier
J
Rodríguez
Boris L
BL
Marrero
Karen
K
García
Hilda
H
García
Luis
L
Fando
Rafael
R
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology; D016667:Bacterial Capsules / Q000096:biosynthesis / Q000276:immunology; D002480:Cellulase / Q000235:genetics; D002771:Cholera / Q000517:prevention & control; D002772:Cholera Toxin / Q000096:biosynthesis / Q000235:genetics; D022121:Cholera Vaccines / Q000276:immunology*; D003013:Clostridium / Q000235:genetics; D004351:Drug Resistance; D024901:Drug Resistance, Multiple, Bacterial; D005813:Genes, Synthetic; D006386:Hemagglutination Tests; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D008666:Metalloendopeptidases / Q000235:genetics; D016254:Mutagenesis, Insertional; D019081:O Antigens / Q000276:immunology*; D011817:Rabbits; D012449:Safety; D013307:Streptomycin / Q000494:pharmacology; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology; D041242:Vibrio cholerae O139 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000276:immunology*
D000907:Antibodies, Bacterial; D022121:Cholera Vaccines; D007074:Immunoglobulin G; D019081:O Antigens; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D002772:Cholera Toxin; C074775:CelA endoglucanase; D002480:Cellulase; D008666:Metalloendopeptidases; C039814:hemagglutinin-protease; D013307:Streptomycin