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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.
Assuntos
Vacinas Bacterianas/imunologia , Bordetella pertussis/imunologia , Proteolipídeos/imunologia , Coqueluche/prevenção & controle , Animais , Proteínas da Membrana Bacteriana Externa/imunologia , Vacinas Bacterianas/administração & dosagem , Feminino , Proteínas de Fímbrias/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Toxina Pertussis/imunologia , Fatores de Virulência de Bordetella/imunologia , Coqueluche/imunologiaRESUMO
BACKGROUND: Leptospirosis is a zoonotic disease of major importance in the tropics where the incidence peaks in rainy seasons. Natural disasters represent a big challenge to Leptospirosis prevention strategies especially in endemic regions. Vaccination is an effective option but of reduced effectiveness in emergency situations. Homeoprophylactic interventions might help to control epidemics by using highly-diluted pathogens to induce protection in a short time scale. We report the results of a very large-scale homeoprophylaxis (HP) intervention against Leptospirosis in a dangerous epidemic situation in three provinces of Cuba in 2007. METHODS: Forecast models were used to estimate possible trends of disease incidence. A homeoprophylactic formulation was prepared from dilutions of four circulating strains of Leptospirosis. This formulation was administered orally to 2.3 million persons at high risk in an epidemic in a region affected by natural disasters. The data from surveillance were used to measure the impact of the intervention by comparing with historical trends and non-intervention regions. RESULTS: After the homeoprophylactic intervention a significant decrease of the disease incidence was observed in the intervention regions. No such modifications were observed in non-intervention regions. In the intervention region the incidence of Leptospirosis fell below the historic median. This observation was independent of rainfall. CONCLUSIONS: The homeoprophylactic approach was associated with a large reduction of disease incidence and control of the epidemic. The results suggest the use of HP as a feasible tool for epidemic control, further research is warranted.
Assuntos
Vacinas Bacterianas/administração & dosagem , Surtos de Doenças/prevenção & controle , Homeopatia/métodos , Leptospira , Leptospirose/epidemiologia , Leptospirose/prevenção & controle , Administração Oral , Estudos de Coortes , Cuba/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Humanos , Incidência , Leptospirose/microbiologia , Vigilância da População , Estações do Ano , Solventes , Resultado do TratamentoRESUMO
This work presents the results from a study of the protein composition of outer membrane vesicles from VA-MENGOC-BC (Finlay Institute, Cuba), an available vaccine against serogroup B Neisseria meningitidis. Proteins were identified by means of SCAPE, a 2DE-free method for proteome studies. More than one hundred proteins were detected by tandem liquid chromatographymass spectrometry analysis of fractions enriched in peptides devoid of histidine or arginine residues, providing a detailed description of the vaccine. A bioinformatic analysis of the identified components resulted in the identification of 31 outer membrane proteins and three conserved hypothetical proteins, allowing the cloning, expression, purification and immunological study of two of them (NMB0088 and NMB1796) as new antigens.
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Antígenos de Bactérias/análise , Proteínas de Bactérias/análise , Vacinas Meningocócicas/química , Neisseria meningitidis Sorogrupo B/química , Proteoma/análise , Vesículas Secretórias/química , Cromatografia Líquida/métodos , Cuba , Humanos , Espectrometria de Massas em Tandem/métodosRESUMO
Vaccines based on outer membrane vesicles (OMV) were developed more than 20 years ago against Neisseria meningitidis serogroup B. These nano-sized structures exhibit remarkable potential for immunomodulation of immune responses and delivery of meningococcal antigens or unrelated antigens incorporated into the vesicle structure. This paper reviews different applications in OMV Research and Development (R&D) and provides examples of OMV developed and evaluated at the Finlay Institute in Cuba. A Good Manufacturing Practice (GMP) process was developed at the Finlay Institute to produce OMV from N. meningitidis serogroup B (dOMVB) using detergent extraction. Subsequently, OMV from N. meningitidis, serogroup A (dOMVA), serogroup W (dOMVW), and serogroup X (dOMVX) were obtained using this process. More recently, the extraction process has also been applied effectively for obtaining OMV on a research scale from Vibrio cholerae (dOMVC), Bordetella pertussis (dOMVBP), Mycobacterium smegmatis (dOMVSM), and BCG (dOMVBCG). The immunogenicity of the OMV has been evaluated for specific antibody induction, and together with functional bactericidal and challenge assays in mice has shown their protective potential. dOMVB has been evaluated with non-neisserial antigens, including with a herpes virus type 2 glycoprotein, ovalbumin, and allergens. In conclusion, OMV are proving to be more versatile than first conceived and remain an important technology for development of vaccine candidates.
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A 5-day workshop on Neisseria vaccines was held in Varadero, Cuba, 17-22 May 2009, and hosted by the Latin American Association for Immunology and the Cuban Society for Immunology, which attracted more than 100 scientists from different parts of the world. The meeting summarizes current knowledge regarding Neisseria species vaccine development, including plain polysaccharide vaccines, conjugate polysaccharides and protein-based vaccines. Main discussion topics were the discovery of new potential antigens with protective capacity, current and new vaccines, pathogenesis and immune response, clinical trials and alternative correlates of protection and manufacture, control and regulation, gonococcus vaccines, and adjuvant as the main component of Neisseria vaccines. Seven keynote addresses, 32 oral presentations, 49 posters and an International Vaccine Course were presented. The meeting was concluded with a 'Hot Topics' session discussing future challenges. This article highlights the most important issues presented.
Assuntos
Gonorreia/prevenção & controle , Meningite Meningocócica/prevenção & controle , Vacinas Meningocócicas , Humanos , Neisseria gonorrhoeae/imunologia , Neisseria gonorrhoeae/patogenicidade , Neisseria meningitidis/imunologia , Neisseria meningitidis/patogenicidadeRESUMO
Introduction Diet is a cornerstone of comprehensive treatment of diabetes mellitus. The macrobiotic diet is low in fat and rich in dietary fiber, vegetables and whole grains, and therefore may be a good therapeutic option. Objective Assess the influence of the Ma-Pi 2 macrobiotic diet on physical, hematologic and biochemical variables, as well as on hypoglycemic medication, in adults with type 2 diabetes mellitus. Materials and Methods A 6-month dietary intervention was carried out in 16 adults with type 2 diabetes mellitus and poor glucide metabolism control (glycosylated hemoglobin, HbA1 >8.5%) receiving treatment at the Diabetic Care Center in Colón, Matanzas province, Cuba. The diet was prepared and served daily by macrobiotic specialists. Type and amount of food consumed and nutritional content were assessed using a weighted food-consumption survey. At onset and termination of the intervention, anthropometric and body composition variables were measured, as were biochemical (glucide and lipid metabolism) and other nutritional safety variables, and hypoglycemic drug use. Results The diet provided sufficient energy and protein. It was low in fat, high in complex carbohydrates and dietary fiber, and provided adequate amounts of vitamins and minerals, except for vitamin B12. At 6 months, anthropometric variables were significantly lower, lean body mass was preserved, and glucide and lipid metabolism was controlled. All participants were able to eliminate insulin treatment, and 25% continued treatment with glibenclamide only. Mean total cholesterol, LDL cholesterol and triglyceride values dropped 16.4%, 22.7% and 37.0%, respectively, while mean HDL cholesterol rose 97.8%. Mean glycemia and HbA1 values also decreased 63.8% and 54.5%, respectively. According to lipid levels and ratios, cardiovascular risk was also considerably reduced. Hemoglobin, total protein, albumin and creatinin levels indicated that nutritional safety was maintained. There were no adverse events. Conclusions In the 6-month intervention, the Ma-Pi 2 macrobiotic diet had a positive influence on weight control, body fat, and glucide and lipid metabolism in patients with type 2 diabetes mellitus. Further research is needed to validate these encouraging results, particularly a clinical trial in which a control group receives the standard diet recommended for diabetic patients.
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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.
Assuntos
Vacinas contra Cólera/administração & dosagem , Cólera/prevenção & controle , Administração Oral , Adolescente , Adulto , Anticorpos Antibacterianos/sangue , Cólera/imunologia , Vacinas contra Cólera/efeitos adversos , Vacinas contra Cólera/imunologia , Cuba , Método Duplo-Cego , Feminino , Humanos , Masculino , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Adulto JovemRESUMO
This paper reviews 20 years of experience and scientific contributions of the Cuban meningococcal BC vaccine (VA-MENGOC-BC®) obtained by the Finlay Institute in Havana, Cuba. The vaccine is the first of its type in the world that is safe, effective, and commercially available for preventing meningococcal disease caused by serogroup B meningococcus; it is also effective against serogroup C. VA-MENGOC-BC® has shown satisfactory results, with no serious adverse events, after application of approximately 55 million doses in some 15 countries. Also included is background information on meningococcal disease, as well as the main characteristics of VA-MENGOC-BC®, the strategy used for controlling meningococcal disease and its prevention in Cuba, and a summary of the main scientific results obtained in basic research, development, clinical evaluation, and post-marketing results (safety, efficacy-effectiveness, post-vaccination adverse events, etc.) in Cuba and elsewhere.
RESUMO
Proteoliposome (PL) has been recently used as a protective intramuscular (i.m.) anti-meningococcal BC vaccine. It induces a preferential Th 1 type of immune response. Nevertheless, mucosal protection is mainly mediated by IgA antibody response, which is not usually induced by i.m. vaccination route. IgA antibody production needs the stimulation of Th3 subpopulation, which is also related to the induction of small dose tolerance. We hypothesized that PL-derived Cochleate can induce a specific mucosal IgA and systemic IgG antibody responses. We could show that mice immunized with two or three intranasal doses of PL-derived Cochleate developed significantly increased levels of local anti PL IgA and systemic IgG antibody responses. Thus, our results suggest that PL-derived Cochleate can be used as a promising immunomodulator and delivery system for the development of mucosal, particularly nasal vaccines.
Assuntos
Adjuvantes Imunológicos/farmacologia , Imunidade nas Mucosas , Proteolipídeos/farmacologia , Vacinas/imunologia , Adjuvantes Imunológicos/administração & dosagem , Administração Intranasal , Animais , Sistemas de Liberação de Medicamentos , Camundongos , Camundongos Endogâmicos BALB C , Proteolipídeos/administração & dosagemRESUMO
Glycoconjugate vaccines provide effective prophylaxis against bacterial infections. To date, however, no commercial vaccine has been available in which the key carbohydrate antigens are produced synthetically. We describe the large-scale synthesis, pharmaceutical development, and clinical evaluation of a conjugate vaccine composed of a synthetic capsular polysaccharide antigen of Haemophilus influenzae type b (Hib). The vaccine was evaluated in clinical trials in Cuba and showed long-term protective antibody titers that compared favorably to licensed products prepared with the Hib polysaccharide extracted from bacteria. This demonstrates that access to synthetic complex carbohydrate-based vaccines is feasible and provides a basis for further development of similar approaches for other human pathogens.