A proteoliposome formulation derived from Bordetella pertussis induces protection in two murine challenge models.

Whooping cough remains a health problem despite high vaccination coverage. It has been recommended that development of new strategies provide long-lasting immunity. The aim of this work was to evaluate the potential of proteoliposomes (PL) extracted from Bordetella pertussis as a vaccine candidate against whooping cough. The size of the B. pertussis PL was estimated to be 96.7 ± 50.9 nm by Scanning Correlation Spectroscopy and the polydispersity index was 0.268. Western blots using monoclonal antibodies revealed the presence of pertussis toxin, pertactin, and fimbriae 3. The Limulus Amebocyte Lisate (LAL) assay showed endotoxin levels lower than those reported for whole cell pertussis licensed vaccines, while the Pyrogen Test indicated 75 ng/mL/Kg. The PL showed high protection capacity in mouse challenge models. There was 89.7% survival in the intracerebral challenge and total reduction of the number of CFU in the intranasal challenge. No significant differences (p > 0.05) were observed between mice immunized with B. pertussis PL and the Cuban DTwP vaccine, whichever challenge model used. These results encouraged us to continue the development of the B. pertussis PL as a component of a new combined vaccine formulated with tetanus and diphtheria toxoids or as a booster dose for adolescents and adults.

Evaluation of enteric-coated tablets as a whole cell inactivated vaccine candidate against Vibrio cholerae.

A vaccine candidate against cholera was developed in the form of oral tablets to avoid difficulties during application exhibited by current whole cell inactivated cholera vaccines. In this study, enteric-coated tablets were used to improve the protection of the active compound from gastric acidity. Tablets containing heat-killed whole cells of Vibrio cholerae strain C7258 as the active pharmaceutical compound was enteric-coated with the polymer Kollicoat(®) MAE-100P, which protected them efficiently from acidity when a disintegration test was carried out. Enzyme-linked immunosorbent assay (ELISA) anti-lipopolysaccharide (LPS) inhibition test and Western blot assay revealed the presence of V. cholerae antigens as LPS, mannose-sensitive haemagglutinin (MSHA) and outer membrane protein U (Omp U) in enteric-coated tablets. Immunogenicity studies (ELISA and vibriocidal test) carried out by intraduodenal administration in rabbits showed that the coating process of tablets did not affect the immunogenicity of V. cholerae-inactivated cells. In addition, no differences were observed in the immune response elicited by enteric-coated or uncoated tablets, particularly because the animal model and immunization route used did not allow discriminating between acid resistances of both tablets formulations in vivo. Clinical studies with volunteers will be required to elucidate this aspect, but the results suggest the possibility of using enteric-coated tablets as a final pharmaceutical product for a cholera vaccine.

Utilidad del modelo animal ratón-pulmón para evaluar la virulencia de posibles cepas vacunales de Shigella spp / Usefulness of lung-mouse animal model to evaluate the virulence of Shigella spp candidate vaccine straims

Shigella flexneri y Shigella sonnei, como cualquier otra especie del género Shigella, se sitúan entre los principalesagentes etiológicos de las enfermedades diarreicas agudas, sobre todo aquellas que ocurren en los países en vías dedesarrollo, aunque por la baja dosis infectante de este enteropatógeno no se excluyen los países desarrollados. Estasituación conlleva a la elaboración de vacunas para prevenir esta enfermedad y la necesidad de un modelo animal quepruebe la eficacia protectora e inmunogénica de posibles candidatos vacunales contra la shigellosis, situación que ha motivado numerosos estudios por la dificultad de demostrar la enteropatía intestinal en los monos y humanos. Lo anteriormente expuesto, más la capacidad de Shigella spp para mostrar resistencia a los ntimicrobianos, motivó la realización de este trabajo. En el mismo se constató la utilidad del modelo animal ratón-pulmón para evaluar la virulencia de candidatos vacunales a partir de este microorganismo. Se utilizó la técnica de inoculación intranasal con una concentración entre 107 y 109 UFC de cepas de Shigella flexneri y Shigella sonnei. Por todos los resultadosobtenidos con el modelo animal ratón-pulmón se concluyó que este modelo puede ser eficiente para los estudiospreclínicos de cualquier candidato vacunal a partir de Shigella spp(AU)

Shigella flexneri and Shigella sonnei, as other species of Shigella, are among the main etiological agents of acute diarrhoeal diseases worldwide, specially in developing countries, although we do not exclude developed ones, because of their low infective dose, between 10 and 100 colonies. This leads to the preparation of vaccines to prevent this illness and the need for an animal model to demonstrate the protective and immunogenic effectiveness of the shigellosis candidate vaccines. Many studies have been carried out since the intestinal enteropathy is difficult to demonstrate in monkeys and humans. The aforementioned and the capacity of Shigella sp to become resistant to antibiotic treatments motivated our study. In it we demonstrated theusefulness of the mouse-lung animal model to evaluate the virulence of vaccine candidates. Intranasal inoculation with Shigella flexneri and Shigella sonnei in concentration on between 107 and 109 CFU was used. The conclusion was that the lung-mouseanimal model can result efficient for preclinical studies of any Shigella spp vaccine candidate(AU)