[Evaluation of the effectiveness of a new vaccine against human leptospirosis in groups at risk]. / Evaluación de la efectividad de una nueva vacuna contra la leptospirosis humana en grupos en riesgo.

In order to evaluate the effectiveness of a new vaccine against human leptospirosis, a prospective cohort study was done with persons in the Cuban province of Holguín who were at risk of becoming ill with leptospirosis. The study included 118,018 persons from 15 to 65 years old who were considered to face either permanent or temporary risk. The vaccinated cohort consisted of 101,137 persons. They received two vaccine doses, 6 weeks apart, of 0.50 mL via deep intramuscular injection into the deltoid muscle of the nondominant arm. The unvaccinated cohort consisted of 16,881 persons. Epidemiological surveillance began 21 days after the application of the second vaccine dose and continued for 1 year. The same criteria for suspected and confirmed cases were maintained throughout the study period. At the end of the surveillance period effectiveness was calculated as being higher than 97%. It is estimated that the vaccination program prevented eight out of ten cases that would have otherwise occurred. Vaccine reactogenicity was also measured in a subsample of 1,500 persons between 15 and 65 years old. The observed symptomatology was low. Slight pain at the injection site was the most frequent symptom (25%). The results of the study indicate the usefulness of the vaccine for disease prevention among people at risk, and its use is thus recommended.

Synthesis of terminal disaccharide elements corresponding to the Ogawa and Inaba antigenic determinant from Vibrio cholerae O1.

Vibrio cholerae O1 LPS terminal mono- and disaccharide elements were synthesized by reduction of the azido group in several 4-amino-4,6-dideoxy-D-mannose mono- and disaccharide derivatives, followed by coupling with 2, 4-di-O-acetyl-3-deoxy-L-glycero-tetronic acid in the presence of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline. This compound represents a useful model in order to elucidate the size of the epitopes which define Ogawa and Inaba serotypes from Vibrio cholerae O1.

[The reactogenicity and immunogenicity of the first Cuban vaccine against human leptospirosis]. / Reactogenicidad e inmunogenicidad de la primera vacuna cubana contra la leptospirosis humana.

A controlled double-blind trial was conducted with the participation of 80 adult volunteers of both sexes, who were randomly divided into groups of 40 individuals each one. The case-base study received the vaccine and the control group was administered placebo to know the safety, the behaviour of reactogenicity, and to star the immunogenicity studies of the first Cuban vaccine against human leptospirosis. The vaccine used in the case-base study was an inactivated and trivalent vaccine containing strains of Leptospira canicola, icterohaemorrhagiae and pomona, since they have the highest circulation in the country. The results obtained showed the inocuity of the vaccine as no adverse severe reactions were detected. The general symptomatology observed was low, where as febricula was the most common general symptom. It appeared during the first 3 days of observation and there were no significant differences between the 2 group. Only a mild pain at the site of the injection was reported as a local symptom, which was more frequent in the vaccinated group than in the control group (7.8 against 1.5%, respectively). The seroconversion obtained was of 29% by microagglutination, and of 34.2% by ELISA. The final results allowed to conclude that this vaccine is safe for human adults at the ages under study, and give the possibility to continue other studies in more advanced stages to complete the requirements for obtaining its license.

Quantification of bovine albumin fraction V in cellular antigens of antileptospirosical Cuban vaccine vaxSpiral.

A solid phase immunoradiometric assay (IRMA) for quantification of bovine albumin fraction V (Bov.Alb.FV) in antileptospirosical Cuban vaccine vaxSpiral is described in the present work. Anti-Bov.Alb.FV IgG raised against rabbit purified by affinity chromatography was used as first antibody. Anti-rabbit IgG labeled by Chloromine-T reaction was used as a tracer and the method has demonstrated to be sensitive with high intra- and inter-assay reproducibility. Eight lots of vaccinal antigens were evaluated and in all of the cases, the bovine albumin fraction V concentration was lower than 1 microgram/mL, as the World Health Organization (WHO) establishes. This IRMA is a simple and sensitive assay and could be used as control method for all human vaccines that use Bov.Alb.FV in their production process, even cellular vaccines.

Biodistribution of the Cuban anti-meningococcal vaccine, VA-MENGOC-BC, in Balb/c mice.

VA-MENGOC-BC is the Cuban vaccine against Neisseria meningitidis BC. Its iodination and biodistribution measurement in Balb/c mice were the main goals of this study. The Chloramine-T method was effective for radiolabelling the proteoliposome, the main vaccine structure. The biodistribution demonstrated that the thyroid (50.4%), muscle (21.5%) and regional lymph nodes (20.5%) were the most radioactive organs and the kinetic of radioactivity was correlated with the primary (muscle, highest values in the first 3 days and lymph nodes, in the first 7 days) and secondary (muscle and lymph nodes, highest values in the first day) response. Early occurrence of slight radioactivity in the spleen was also observed. This was the first time that the iodination and biodistribution of this vaccine was carried out. The present study corroborated that the time selected in previous trials to obtain the lymph nodes and spleen cell, after a first (7 days) and second (3 days) dose, was actually the optimal for in vitro studies.

Evaluation of the antimeningococcal immunoglobin activity against five strains of Neisseria meningitidis group B from Latin America using mice as model.

To know the activity of antimeningococcal immunoglobulin, Balb/c mice of 18-22 g of body weight were challenged with 5 serotype B strains of Neisseria meningitidis (Nm) isolated from patients of different Latin American countries. The specific antimeningococcal Ig was extracted from the serum of volunteers previously vaccinated with the antimeningococcal BC vaccine VA-MENGOC-BC (Finlay Institute, Havana, Cuba). The Ig was intraperitoneally (IP) administered in a unique dose of 10 mg/mouse. The strains A, B, C, CH and D were inoculated IP in the following charges: strain A, 20 LD50; B, 25 LD50; C, 44.5 LD50; CH, 36 LD50, and D, 200, 20 and 2 LD50. For each strain, a control group received living bacteria and virulent stimulating factor (VSF). The Ig was injected 30 min before or 30 min after the challenge dose had been given, except for strain D, which only received the Ig 30 min after the challenge. As VSF, 0.5 mg of iron in the form of iron dextran was used. The experiment was analyzed considering the survival time after the challenge for each strain compared to the corresponding control group (C). When the Ig was used 30 min before the challenge, the protection period for the A strain was (C:18.1h) more than 72h (P<0.001) and 100% survival; for the B strain, (C:29.5h) 42h (P<0.05) and almost 20% survival; for the C strain (C:16.5h) 35h (P<0.01) with a 40% survival, and the CH strain (C:18.1h) 26.5h (P<0.02), with a 20% survival. When the Ig was injected 30 min after the challenge, the average survival time and the survival for the A strain was 28h (P<0.05) with 62.5%; for the B strain it was 42 h (P<0.005) and 0.0%; for the C strain 27.3 h (P<0.05) and 30%; for the CH strain 25.8h (P<0.05) and 0.0%, and for the D strain 19.1h, 26h, and more than 72h with a 0.0%, 60% and 100%, depending on the challenging dose. In general, the specific Ig used showed a protective effect in mice against the different Latin American strains tested. Additionally, the experimental model proved to be useful for the study of the antimeningococcal human Ig.