title: TLP01, an mshA mutant of Vibrio cholerae O139 as vaccine candidate against cholera.
abstract: No commercially live vaccine against cholera caused by Vibrio cholerae O139 serogroup is available and it is currently needed. Virulent O139 strain CRC266 was genetically modified by firstly deleting multiple copies of the filamentous phage CTXφ, further tagging by insertion of the endoglucanase A coding gene from Clostridium thermocellum into the hemagglutinin/protease gene and finally deleting the mshA gene, just to improve the vaccine biosafety. One of the derived strains designated as TLP01 showed full attenuation and good colonizing capacity in the infant mouse cholera model, as well as highly immunogenic properties in the adult rabbit and rat models. Since TLP01 lacks MSHA fimbriae, it is refractory to infection with another filamentous phage VGJφ and therefore protected of acquiring CTXφ from a recombinant hybrid VGJφ/CTXφ. This strategy could reduce the possibilities of stable reversion to virulence out of the human gut. Furthermore, this vaccine strain was impaired to produce biofilms under certain culture conditions, which might have implications for the strain survival in natural settings contributing to vaccine biosafety as well. The above results has encouraged us to consider TLP01 as a live attenuated vaccine strain having an adequate performance in animal models, in terms of attenuation and immunogenicity, so that it fulfills the requirements to be evaluated in human volunteers.
authors.affiliation: Departamento de Biología Molecular, División de Enfermedades Infecciosas, Centro Nacional de Investigaciones Científicas, Ave 25 Esq 158, AP 6412, La Habana, Cuba. talena.ledon@cnic.edu.cu
authors.forename: Talena
authors.initials: T
authors.lastname: Ledón
authors.forename: Beatriz
authors.initials: B
authors.lastname: Ferrán
authors.forename: Celso
authors.initials: C
authors.lastname: Pérez
authors.forename: Edith
authors.initials: E
authors.lastname: Suzarte
authors.forename: Joivier
authors.initials: J
authors.lastname: Vichi
authors.forename: Karen
authors.initials: K
authors.lastname: Marrero
authors.forename: Reinaldo
authors.initials: R
authors.lastname: Oliva
authors.forename: Rafael
authors.initials: R
authors.lastname: Fando
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D057138:Bacterial Shedding; D001483:Base Sequence; D018441:Biofilms; D002771:Cholera / Q000276:immunology / Q000517:prevention & control; D022121:Cholera Vaccines / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D004195:Disease Models, Animal; D005243:Feces / Q000382:microbiology; D036781:Fimbriae Proteins / Q000235:genetics / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology; D037601:Mannose-Binding Lectin / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D016415:Sequence Alignment; D017384:Sequence Deletion / Q000235:genetics; D018709:Statistics, Nonparametric; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D041242:Vibrio cholerae O139 / Q000235:genetics / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D022121:Cholera Vaccines; D037601:Mannose-Binding Lectin; C101032:MshA protein, Vibrio cholerae; D014613:Vaccines, Attenuated; D036781:Fimbriae Proteins