Randomized, double-blind, placebo-controlled trial to evaluate the safety and immunogenicity of live oral cholera vaccine 638 in Cuban adults
Introduction
Vaccination against cholera continues to be a feasible strategy against this infection. It has been demonstrated that oral immunization with genetically attenuated cholera strains stimulates an efficient mucosal response [1]. Previous studies carried out with CVD 103HgR (classic biotype) and Peru-15 (El Tor biotype) vaccines, indicate that both vaccines are well tolerated, immunogenic and protective in challenge clinical trials in humans [2], [3], [4], nevertheless their effectiveness in endemic areas still remains uncertain [5].
A group of genetically attenuated Vibrio cholerae strains O1 and O139 serogroups have been obtained in Cuba [6], [7], [8]. Among them, the attenuated 638 strain V. cholerae O1 El Tor Ogawa proved to be well tolerated and immunogenic in a single dose ranging from 107 to 109 CFU [9]. With 109 CFU dose, this strain is able to provide protection against the diarrhea caused by a pathogenic strain V. cholerae O1 El Tor Ogawa [10]. In a previous challenge clinical trial, under quarantine hospitality facilities, a group of healthy volunteers were immunized with a single dose of 109 CFU of the 638 strain and others received placebo as a control group. The protection conferred by previous immunization with the 638 strain against colonization and diarrhea caused by the infection with the virulent 3008 V. cholerae strain was also demonstrated in that study [10].
Thus, these results encouraged the pharmaceutical development of a lyophilized live attenuated vaccine. This vaccine was formulated under good manufacturing practice procedures and contains the 638 strain as its active pharmaceutical ingredient [11].
A phase I–II clinical trial was carried out in healthy human volunteers to evaluate safety, reactogenicity and immunogenicity of 2 × 109 CFU single dose of the live oral cholera vaccine 638.
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Study design
Thirty-six healthy female and male volunteers from 18 to 40 years working at Scientific Institutions of the City of Havana, Cuba, were enrolled in a randomized, double-blind, placebo-controlled inpatient clinical trial, conducted at the Unit for Isolation of Biological Risks at Tropical Medicine Institute “Pedro Kourí” (IPK), in the City of Havana, Cuba, after they gave an informed consent according to the guidelines of the State Regulatory Authority for Medicine Control from the Ministry of
Clinical response to 638 vaccine
No significant changes were seen on volunteer's Hematological and Biochemical Laboratory parameters tested after vaccine or placebo feeding. No clinical manifestations were observed or reported during the first hour after vaccine administration. Nobody had serious adverse event during the clinical follow-up time of this study. None of general adverse events registered during the entire follow-up period of 30-day treatment feeding were life-threatening for volunteers involved in this study.
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Discussion
In this study, the absence of serious or severe adverse events or significant changes in volunteer's Hematological and Biochemical Laboratory parameters shown that the 638 vaccine is safe and confirms data from previous studies [8], [9], [10]; where a fresh culture of the 638 strain was used as oral the inoculum. Considering all subjects were clinically examined and exhaustively selected to participate in this study, we expected a higher incidence and an earlier beginning of adverse event in
Acknowledgments
We would like to thank the performance of the infirmary staff of the isolation ward at the Institute for Tropical Medicine Pedro Kourí, in the City of Havana, Cuba, for their professional performance. We specially acknowledge the voluntary participation of all the subjects enrolled in the trial. Finally we want to warmly thank Orquidea Biart la Rosa, for her careful linguistic revision of the English language of this article.
References (21)
- et al.
Taggin a Vibrio cholerae El Tor candidate vaccine strain by disruption of its hemagglutinin/protease gene using a novel reporter enzyme, Clostridium thermocellone endogluconase A
Vaccine
(1996) - et al.
Process development for Cuban cholera vaccine based on the attenuated strain Vibrio cholerae 638
Vaccine
(2006) - et al.
Immunity and vaccine development
- et al.
Randomized, double-blind, placebo-controlled multicenter trial of the efficacy of a single dose of live oral cholera vaccine CVD 103-HgR in preventing cholera following challenge with Vibrio cholerae O1 El Tor Inaba three months after vaccination
Infect. Immun.
(1999) - et al.
Peru-15, an improved live attenuated oral vaccine candidate for Vibrio cholerae O1
J. Infect. Dis.
(1995) - et al.
Randomized, controlled human challenge study of safety, immunogenicity, and protective efficacy of a single dose of Peru’-15, a live attenuated oral cholera vaccine
Infect. Immun.
(2002) - et al.
Vaccination strategies for mucosal immune responses
Clin. Microbiol. Rev.
(2001) - et al.
Genetic manipulation of Vibrio cholerae for vaccine development: construction of live attenuated El Tor candidate vaccine strains
Arch. Med. Res.
(1996) - et al.
Selección de cepas atenuadas de Vibrio cholerae para la obtención de candidatos vacunales atenuados orales contra cólera
Rev. Cubana Med. Trop.
(2005) - et al.
Preliminary assessment of the safety and immunogenicity of a new CTX-negative, hemagglutinin/protease-defective El Tor strain as a cholera vaccine candidate
Infect. Immun.
(1999)
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These authors contributed equally to the results presented in this article.