Randomized, double-blind, placebo-controlled trial to evaluate the safety and immunogenicity of live oral cholera vaccine 638 in Cuban adults.

A randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the safety, reactogenicity and the immunogenicity of a 2 x 10(9)CFU dose of the 638 lyophilized live attenuated cholera vaccine for oral administration, formulated and produced at Finlay Institute, City of Havana, Cuba. Thirty-six healthy female and male adult volunteers from 18 to 40 years old were involved, clinically examined and laboratory tested after the informed consent signature. Adverse events were monitored and seroconversion rates and geometrical mean titer (GMT) of vibriocidal antibodies were tested in volunteer's sera samples. Neither serious adverse events nor other damages to the volunteers due to vaccine or placebo feeding were reported during the clinical follow-up period of this study; none of the adverse events registered within the first 72 h after inoculation were life-threatening for volunteers. Neither severe nor moderate adverse events were reported. Sixty-one percent of subjects showed mild expected adverse events in an interval lower than 24h up to the first 72 h, 75% of these in the vaccinated group and 18% in the placebo group. Fourteen days after inoculation the GMT of vibriocidal antibodies in the vaccine group significantly increased in comparison to the placebo group. All subjects in the vaccine group (24) seroconverted (100%). Results show that this vaccine is safe, well tolerated and immunogenic in healthy female and male volunteers.

Selección de cepas atenuadas de Vibrio cholerae para la obtención de candidatos vacunales atenuados orales contra el cólera / Selection of attenuated Vibrio cholerae strains to obtain oral attenuated candidate vaccines against cholera

Se desarrolló una metodología para la selección de cepas de Vibrio cholerae O1 y O139 modificadas genéticamente, con el objetivo de obtener candidatos vacunales atenuados orales contra el cólera. A las cepas modificadas se les realizó caracterización microbiológica, susceptibilidad bacteriana y diferentes pruebas biológicas (dosis letal media, capacidad colonizadora, adherencia en ratones, intestino ligado e inoculación intraduodenal en conejos como pruebas de virulencia y potencia). Las cepas 81, 638, 638T y 1333 fueron evaluadas en ensayos clínicos para determinar su reactogenicidad e inmunogenicidad. Todas las cepas fueron sensibles a la tetraciclina y doxiclicina y mostraron su atenuación e inmunogenicidad en modelos animales, resultando las cepas 638 y 1333 inmunogénicas y no reactogénicas en voluntarios