Randomized, double-blind, placebo-controlled trial to evaluate the safety and immunogenicity of live oral cholera vaccine 638 in Cuban adults
Instituto Finlay, Centro de Investigación, Desarrollo y Producción de Vacunas, P.O. Box 16017, La Lisa, Ciudad de La Habana 11600, Cuba. Vaccine
(Impact Factor: 3.62).
09/2009; 27(47):6564-9. DOI: 10.1016/j.vaccine.2009.08.042
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.
Available from: Jon Kim Andrus
- "Although two single-dose oral vaccine candidates are in clinical development,31–33 no such vaccine is currently licensed and produced. Single-dose vaccines would greatly improve the prospects of vaccination during or before a cholera outbreak, regardless of whether for pre-emptive or reactive purposes. "
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ABSTRACT: Deployment of oral cholera vaccine (OCV) on the Island of Hispaniola has been considered since the emergence of the disease in October of 2010. At that time, emergency response focused on the time-tested measures of treatment to prevent deaths and sanitation to diminish transmission. Use of the limited amount of vaccine available in the global market was recommended for demonstration activities, which were carried out in 2012. As transmission continues, vaccination was recommended in Haiti as one component of a comprehensive initiative supported by an international coalition to eliminate cholera on the Island of Hispaniola. Leveraging its delivery to strengthen other cholera prevention measures and immunization services, a phased OCV introduction is pursued in accordance with global vaccine supply. Not mutually exclusive or sequential deployment options include routine immunization for children over the age of 1 year and campaigns in vulnerable metropolitan areas or rural areas with limited access to health services.
Available from: Hilda María García
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ABSTRACT: El cólera constituye un problema de salud para muchos países en el mundo: las elevadas tasas de morbilidad y mortalidad registradas en los últimos años inquietan a la comunidad científica, pues el aumento de su incidencia podría generar una crisis global en su control. Existen factores claves en su reemergencia, entre ellos están el debilitamiento general de las actividades de salud pública, sobre todo las involucradas en la vigilancia y el deterioro de los laboratorios encargados de identificar cuanto antes a los microorganismos emergentes, así como la circulación en África y Asia de nuevas cepas de Vibrio cholerae O1 El Tor, las que producen la toxina del cólera clásico y reemplazan a la original del biotipo El Tor, ocasionando manifestaciones clínicas más graves,esta situación que representa un obstáculo importante para el control de esta enfermedad. En la lucha contra ésta en casos de desastre, la Organización Mundial de la Salud no recomienda el uso de las vacunas actuales, porque ocurre una rápida disminución en la protección, lo que da un sentido falso de la seguridad, debiéndose dirigirlos recursos a los métodos de control más útiles.Dada la repercusión global que implica la reemergencia del cólera, en este trabajo se exponen algunos aspectos epidemiológicos, así como consideraciones en torno a las medidas de prevención y el control de esta entidad clínica, a partir de la revisión de diferentes fuentes de información actualizadas y la exposición de nuevos conceptos sobre su control, observaciones que serán de utilidad e interés para profesionales de todos los niveles de la atención sanitaria.
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ABSTRACT: Cholera caused by the O139 serogroup still remains a public health concern in certain regions of the world and the existing O1 vaccines do not cross-protect cholera caused by this serogroup. An aminolevulinic acid (ALA) auxotroph vaccine candidate against the O139 serogroup, designated as VCUSM2, was recently developed. It was found to be immunogenic in animal model studies but showed mild reactogenic effects due to the presence of two intact copies of Vibrio cholerae toxin (CTX) genetic element. In the present study we have modified the ctx operon by systematic allelic replacement methodology to produce a mutant strain, designated as VCUSM14. This strain has two copies of chromosomally integrated and mutated ctxA gene, encoding immunogenic but not toxic cholera toxin A subunit (CT-A). The amino acids arginine and glutamic acid at position 7th and 112th, respectively, in CT-A of VCUSM14 were substituted with lysine (R7K) and glutamine (E112Q), respectively. Two copies of the ace and zot genes present in the ctx operon were also deleted. Cholera toxin-ELISA using GM1 ganglioside showed that the both wild type CT and mutated CT were recognized by anti-CT polyclonal antibodies. VCUSM14 produced comparatively less amount of antigenic cholera toxin when compared to the VCUSM2 and Bengal wild type strain. VCUSM14 did not elicit fluid accumulation when inoculated into rabbit ileal loops at doses of 10(6) and 10(8) CFU. The colonization efficiency of VCUSM14 was one log lower than the parent strain, VCUSM2, which can be attributed to the ALA auxotrophy and less invasive properties of VCUSM14. VCUSM14, thus a non-reactogenic auxotrophic vaccine candidate against infection by O139 V. cholerae.
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