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The attenuated strain Vibrio cholerae 638 (O1, El Tor, Ogawa) is the active ingredient of oral vaccine candidate CV638, product well tolerated and immunogenic in several studies with healthy volunteers. The administration of live attenuated biological agent involves its excretion in the feces of vaccine recipients. Then in the regulatory context, there is concern about its potential environmental impact and the possibility of reversion to virulence. This paper is an experimental approach to the possible performance of such strain on the environment. It was assessed the survival of VC638 using water from different sources in several laboratory conditions. The results suggest that this strain has no advantages over its wild type parental strain to survive in optimum or minimal growth conditions. Strain susceptibility to stress conditions that included sodium dodecyl sulfate and hyperosmotic environment was also determined. The results suggest that the vaccine strain does not possess properties that favor its performance against these agents. In addition, it was tested their resistance to horizontal gene transmission, concluding that VC638, as toxigenic strains currently circulating in the Caribbean, is resistant to natural transformation in the presence of chitin. The transformation frequency of VC638 is 10³ times lower than that of its toxigenic parental strain. Finally, VC 638 showed no signs of possible advantages to compete and survive in natural environments. [ABSTRACT FROM AUTHOR]

El artículo discurre sobre el desarrollo de vacunas profilácticas contra el virus del papiloma humano (VPH). Los autores comentan sobre los riesgos de contraer el cáncer cervicouterino via el VPH y examinan la importancia de estas vacunas de segunda y tercera generación contra el VPH, incluyendo Cervarix y Gardasil.

El artículo discurre sobre la bacteria bodetella pertussis, la toxina pertúsica y los alelos relacionados. Los autores comentan sobre las vacunas anti-pertúsicas, la regulación genética y los antígenos utilizados para inducir inmunidad. Otros temas incluyen las reacciones en cadena de la polimerasa (PCR) y una PCR alelo específica.

The active ingredient of the live vaccine candidate CV638 is the genetically attenuated strain Vibrio cholerae 638, which was obtained from the wild type toxigenic V. cholerae strain C7258, by deleting the cholera toxin genes (ctxAB). The use of live attenuated vaccines requires assays that ensure the stability of the attenuating mutation; as well as the lack of wild type toxigenic infectious cells. The present study was aimed at designing a nested PCR assay specific for ctxAB genes and evaluating its detection limit in lots of CV638 contaminated with known amounts of the toxigenic strain C7258Kn. One primer pairs specific for ctxAB genes were designed and PCR conditions respect to annealing temperature and MgCl2 concentration was established. The detection limit of the nested PCR assay of V. cholerae toxigenic bacteria was determined in CV638 preparations contaminated with increasing amounts of toxigenic vibrions. The detection limit was evaluated statistically and it was found to be ~ 50 colony forming units (CFU) of the toxigenic strain per CV638 dose, value lower than the smaller infective dose informed for V. cholerae (10³ CFU). Once validated, the described nested PCR assay could be used as a purity control assay during the quality control testing of CV638. [ABSTRACT FROM AUTHOR]

Introduction: live attenuated oral Vibrio cholerae Ol El Tor, Ogawa strain 638 has demonstrated to be well tolerated and immunogenic when administrated orally in studies carried out in healthy volunteers., Objectives: to evaluate the protection against cholera infection in a challenge clinical trial, for the technological and pharmaceutical scale-up of this vaccinal candidate as active ingredient at industrial level., Methods: a total of 21 healthy volunteers were involved in this trial; the vaccine candidate was administered to 12 of them and the remaining nine were given the placebo. Twenty eight days later, all of them received an infective dose of a V. cholerae virulent strain., Results: diarrheas were observed in 7 out of 9 placebos whereas not a single vaccinated volunteer showed diarrheas. More frequent and intense loose stools were found in the placebo volunteers with O-blood group. All volunteers in he placebo group excreted V. cholerae, but only three (25%) out of the 12 vaccinated volunteers did so., Conclusion: in this challenge clinical trial model, the 638 strain proved to protect people against the diarrhea caused by a virulent V. cholerae strain.