Attenuated strains of vibrio cholerae with improved biological safety features in freeze dried form for oral vaccination

• Main Authors: MOREIRA HERMANDEZ TOMAS MARCELINO, URRA VILLAVICENCIO CARIDAD, SUZARTE PORTAL EDITH, DELGADO RODRIGUEZ HERMINIA D.L, SILVA LARRANAGA YUSSUAN, MARRERO DOMINGUEZ KAREN, LEDON PEREZ TALENA Y, CAMPOS GOMEZ JAVIER, RODRIGUEZ GONZALEZ BORIS L, MARTINEZ GUTIERREZ ERIEL, FANDO CALZADA RAFAEL A
• Format: Patent
• Language: English
• Published: 29.03.2007
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; HUMAN NECESSITIES; HYGIENE; MEASURING; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; ORGANIC CHEMISTRY; PEPTIDES; PHYSICS; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; TESTING; TESTING STATIC OR DYNAMIC BALANCE OF MACHINES ORSTRUCTURES; TESTING STRUCTURES OR APPARATUS NOT OTHERWISE PROVIDED FOR; VINEGAR; WINE

The present invention discloses new live attenuated strains for oral immunization against cholera that are provided in freeze dried formulations for long term storage and administration to humans. These strains combine the two most important properties of live attenuated cholera vaccine candidates. One such property is being well tolerated by people ingesting them. This was achieved by virtue of mutations already described in the art. The second property is having enhanced environmental safety due to the absence of VGJPhi DNA in their genomes and also due to null mutations in the mshA gene or other spontaneous mutations conducive to the lack of MSHA type IV fimbria on the bacterial surface. This was done envisioning that VGJPhi is a filamentous phage able to recombine with CTXPhi and disseminate the cholera toxin genes. This VGJPhi phage as well as the VGJPhi-CTXPhi recombinants uses the MSHA fibers as receptor. Being devoid of MSHA fimbria the vaccine candidates are protected from acquiring CTXPhi from the recombinant hybrid VGJPhi-CTXPhi. Being devoid of VGJPhi, the vaccine candidates are impaired in the dissemination of CTXPhi, via VGJPhi.