Short-term and long-term antibody response by mice after immunization against Neisseria meningitidis B or diphtheria toxoid

Serogroup B Neisseria meningitidis (MenB) is a major cause of invasive disease in early childhood worldwide. The only MenB vaccine available in Brazil was produced in Cuba and has shown unsatisfactory efficacy when used to immunize millions of children in Brazil. In the present study, we compared the specific functional antibody responses evoked by the Cuban MenB vaccine with a standard vaccine against diphtheria (DTP: diphtheria, tetanus, pertussis) after primary immunization and boosting of mice. The peak of bactericidal and opsonic antibody titers to MenB and of neutralizing antibodies to diphtheria toxoid (DT) was reached after triple immunization with the MenB vaccine or DTP vaccine, respectively. However, 4 months after immunization, protective DT antibody levels were present in all DTP-vaccinated mice but in only 20% of the mice immunized against MenB. After 6 months of primary immunization, about 70% of animals still had protective neutralizing DT antibodies, but none had significant bactericidal antibodies to MenB. The booster doses of DTP or MenB vaccines produced a significant antibody recall response, suggesting that both vaccines were able to generate and maintain memory B cells during the period studied (6 months post-triple immunization). Therefore, due to the short duration of serological memory induced by the MenB vaccine (VA-MENGOC-BC® vaccine), its use should be restricted to outbreaks of meningococcal disease.

Diphtheria-neutralizing antibody levels in healthy adults from Rio de Janeiro, Brazil

In Brazil, until 2004, the immunization policy against diphtheria involved childhood vaccination with no official routine booster dose administered after 15 years of age. This study assessed functional antibody levels against diphtheria among blood donors. A total of 140 blood samples were collected, and diphtheria antitoxin levels were evaluated by Vero cell neutralization test. The mean age of the population was 34 years old (range: 18-61 years); 37.8 percent females and 62.2 percent males. Overall, 30.7 percent (95 percent, CI: 23.4-38.7) individuals presented neutralizing antitoxin antibody titers < 0.01 IU/ml; 42.1 percent (95 percent, CI: 34.1-50.4) showed values between 0.01-0.09 IU/ml and, 27.1 percent (95 percent, CI: 20.2-34.9) had ³ 0.1 IU/ml. In the subgroup of individuals with history of diphtheria immunization during childhood (85 percent), a number of 28.5 percent showed unprotective levels of circulating neutralizing antibody (< 0.01 IU/ml). Despite the continuous progress of immunization programs directed to Brazilian population, currently healthy adults remain susceptible to diphtheria.

An antibody induction method in mice for the potency assays of diphtheria and tetanus components in combined vaccines.

Eleven batches of Adsorbed Diphtheria-Tetanus (DT) vaccines and thirteen batches of Adsorbed Diphtheria-Pertussis-Tetanus (DTP) vaccines were tested for the potency of diphtheria and tetanus components by an Antibody Induction Method (AIM) developed in mice. The potency results obtained were found comparable and did not show any statistically significant difference with those obtained by WHO recommended lethal challenge tests for diphtheria in guinea pigs and for tetanus in mice. AIM in mice is more economical as both diphtheria and tetanus components of combined vaccine can be tested in the same experiment and the procedure also eliminates the use of guinea pigs required in the lethal challenge/conventional tests. The data obtained while testing tetanus component by the conventional antibody induction (IP) method in guinea pigs suggests that minimum requirements laid down in i.p. is too low which may be fixed as at least 3 out of 9 guinea pig sera and should contain > or = 4 units of tetanus antitoxin per ml.

Quantitation of tetanus and diphtheria antitoxins in mouse sera by indirect haemagglutination.

Serum samples obtained from 75 groups of mice immunized with various doses of adsorbed tetanus vaccine, adsorbed diphtheria-tetanus vaccine and adsorbed diphtheria-tetanus-pertussis vaccine were titrated for tetanus antitoxin content by an in-vitro indirect haemagglutination (IHA) and by toxin neutralization test (TN) in mice. From these serum samples of 49 groups of mice which were immunized with combined vaccine containing diphtheria toxoid were titrated for their diphtheria antitoxin content by IHA and by i.d. toxin neutralization test (TN) in guinea pigs. Good correlations were found between the estimates obtained by in-vitro IHA and in vivo TN tests in both tetanus and diphtheria antitoxin titrations. The minimum level of tetanus or diphtheria antitoxin detectable by IHA was 0.00039 IU/ml. It is concluded that IHA is a simple, sensitive and reproducible alternative test which can replace the animal TN tests for the estimation of tetanus and diphtheria antitoxins and could reliably be used in the potency assay of tetanus and diphtheria toxoids of combined vaccines based on antibody induction in mice.

Immunity to diphtheria in women of childbearing age in Delhi in 1994: evidence of continued Corynebacterium diphtheriae circulation.

Blood samples from 171 full-term pregnant women (aged 18-38 years) of middle socioeconomic status from Delhi were tested for diphtheria antitoxins by indirect hemagglutination (IHA) test. History of primary immunization/clinical diphtheria during childhood was not ascertainable, but none had been revaccinated against diphtheria at any time. About 94% women had very high antitoxin titers (> or = 0.125 IU/ ml); none had antitoxin titer less than 0.015 IU/ml, the minimum protective level. The titers were uniformly high in all age groups. However, women having 2 or more children had significantly higher antitoxin titers than those having no or one child (p < 0.01). The results from this study and historical data on diphtheria in Delhi are compatible with continued transmission of C. diphtheriae in recent times in Delhi which is of sufficient magnitude to boost the antitoxin levels in adults, especially mothers having two or more children. The study highlights the need of increasing the immunization coverage with DPT among children to reduce the transmission of Corynebacterium diphtheriae.

Inmunización con hormona liberadora de gonodatropinas / Immunization with gonodatropins-releasing hormone

El uso de la inmunización contra la hormana liberadora de gonadotropinas (GnRH), es un método empleado con fines contraceptivos. Se estudió el efecto de una vacuna de GnHR unida al toxoide diftérico sobre el aparato reproductor de la rata blanca adulta y los niveles plasmáticos de testosterona (T). Se encontró que al tercer mes de haber sido inmunizados los animales con GnHR se produjo una significativa pérdida de peso de los testículos, vesículas seminales y próstata. El peso corporal no se afectó. Al estudio histológico se encontró que en los testículos existía una marcada afectación en la espermatogénesis, llegando en algunos animales a haber solamente células de Sertoli. Se concluye que la combinación empleada de GnHR con el toxoide diftérico, así como el esquema de vacunación empleado afectan profundamente al aparato reproductor de la rata. Desconocemos si el proceso deletéreo inducido por la vacunación es reversible o no

Vacunas duple: estudio de la reactogenicidad e inmunogenicidad de las preparaciones importada y cubanas (con diferentes dosis de toxoides) / Duplex vaccine: study on reactogenicity and immunogenicity of cuban and imported preparations(with different doses of toxoid)

Se realiza un estudio de la reactogenicidad e inmunogenicidad de vacunas combinadas contra la difteria y tétanos, importadas y de producción nacional(con diferentes dosis de toxoides), en un grupo de 40 escolares. Se comparan los efectos colaterales producidos por las preparaciones utilizadas. Sedetermina el estado inmunitario previo a la vacunación con respecto a la difteria y el tétano, así como el incremento de los títulos de antitoxina. Se utiliza el método ultra micro ELISA(UME) en el sistema ultra micro analítico (SUMA). Se comprueba la tolerancia y poder inmunogénico de las vacunas. Se recomienda continuar las investigaciones y utilizar el método UME en el SUMA, para los trabajos de terreno

Evaluación de la reactogenicidad de las vacunas duple importadas y cubanas (con iguales dosis de toxoides) / Assessing the reactogenicity of cuban and imported duple vacines (with the same dose of toxoid)

Se realiza un estudio de la reactogenicidad e inmunogenicidad de vacunas combinadas contra la difteria y el tétanos, importada y de producción nacional(con iguales dosis de toxoides); en un grupo de escolares se comparan los efectos colaterales producidos por las preparaciones utilizadas. Se determina el estado inmunitario previo a la vacunación con respecto a la difteria y tétanos, así como el incremento de los títulos de antitoxinas. Se utiliza el método ultra micro ELISA(UME)en el sistema ultra micro analítico(SUMA). Se comprueba la tolerancia y poder inmunogénico de las vacunas. Se recomienda continuar lasinvestigaciones y utilizar el método UME el SUMA

Effect of different concentrations of diphtheria toxoid & aluminum phosphate on potency of diphtheria component in DPT vaccines.

An effort was made to determine the optimum concentration of diphtheria toxoid in combination with aluminum phosphate gel in DPT vaccines which may give a safe, potent and economical preparation. The effect of four different concentrations of aluminum phosphate and three different antigenic concentrations of diphtheria toxoid on potency of diphtheria component in DPT vaccine was assessed. A gradual increase in potency was seen with increase in toxoid concentration and a gradual decrease in potency with the increase in aluminum phosphate content. Vaccines made with minimum quantities of toxoid (30 Lf/ml) and aluminum phosphate (3 mg/ml) were found to be highly satisfactory. Vaccines prepared with high antigenic purity toxoid have better potency, as compared to those prepared with a relatively low antigenic purity toxoid.

Febrile response in malnutrition

The febrile response to a standard dose of triple (DPT) vaccine was assessed in sixteen malnourished children before and after recovery. The increase in temperature was significantly lower in the malnourished children (p < 0.005)

Respuestas inmunológica en niños inmunizados con tres dosis de DPT y seis años después

Las enfermedades infecciosas Difteria, Tosferina y Tétanos constituyen problemas de salud pública en países subdesarrollados como Guatemala. Problemas como la falta de cobertura al total de niños susceptibles y manejo inadecuado de cadena del frío de las vacunas son reflejo de problemas socio-económicos del país, que afectan al control de enfermedades prevenibles por una vacunación adecuada. El objetivo principal de este trabajo fue evaluar la respuesta de anticuerpos inducida por la DPT en niños después de tres dosis y a los seis años. La determinación de los anticuerpos anti difteria, pertussis y tetanos se hizo con el método del ensayo inmunenzimático en fase sólida ELISA. Los resultados de este trabajo demonstraron que la respuesta de anticuerpos contra la difteria en niños después de tres dosis fue de 94% positivos y un fallo de 6% en la ciudad de Guatemala y de 89% positivos y un fallo de 11% en la ciudad de Escuintla. En niños, a los 6 años de haber sido vacunados en la ciudad de Guatemala la positividad fue de 66% y el fallo de 34%. La respuesta a la vacuna anti pertussis fue la siguiente: en los niños de la ciudad de Guatemala con tres dosis fueron de 80.8% positivos y 19.2% de fallo. En la aldea de Cacte en Petén fue de 72.3% de positividad y 27.7% de fallo y en los niños de la ciudad de Guatemala a los seis años de vacunados 88.8% de positividad y 11% de fallo. Los resultados a la vacuna anti tetánica fueron: en los niños de la ciudad de Guatemala con tres dosis fue de 93.9% de positivos y un 5.9% de fallo y en el municipio de Mixco 94% de positivos y 6% de fallo y en niños estudiados después de 6 años de la inmunización en la ciudad de Guatemala fue de 88.8% positivos y 11% negativos...