Collaborative study on saccharide quantification of the Haemophilus influenzae type b component in liquid vaccine presentations.

Before release onto the market, it must be demonstrated that the total and free polysaccharide (poly ribosyl-ribitol-phosphate, PRP) content of Haemophilus influenzae type b (Hib) vaccine complies with requirements. However, manufacturers use different methods to assay PRP content: a national control laboratory must establish and validate the relevant manufacturer methodology before using it to determine PRP content. An international study was organised by the World Health Organization (WHO), in collaboration with the Biological Standardisation Programme (BSP) of the Council of Europe/European Directorate for the Quality of Medicines & HealthCare (EDQM) and of the European Union Commission, to verify the suitability of a single method for determining PRP content in liquid pentavalent vaccines (DTwP-HepB-Hib) containing a whole-cell pertussis component. It consists of HCl hydrolysis followed by chromatographic separation and quantification of ribitol on a CarboPac MA1 column using high-performance anion exchange chromatography coupled with pulsed amperometric detection (HPAEC-PAD). The unconjugated, free, PRP is separated from the total PRP using C4 solid-phase extraction cartridges (SPE C4). Ten quality control laboratories performed two independent analyses applying the proposed analytical test protocol to five vaccine samples, including a vaccine lot with sub-potent PRP content and very high free PRP content. Both WHO PRP standard and ribitol reference standard were included as calibrating standards. A significant bias between WHO PRP standard and ribitol reference standard was observed. Study results showed that the proposed analytical method is, in principle, suitable for the intended use provided that a validation is performed as usually expected from quality control laboratories.

Infants' exposure to aluminum from vaccines and breast milk during the first 6 months.

The success of vaccination programs in reducing and eliminating infectious diseases has contributed to an ever-increasing number of vaccines given at earlier ages (newborns and infants). Exposure to low levels of environmental toxic substances (including metals) at an early age raises plausible concerns over increasingly lower neuro-cognitive rates. Current immunization schedules with vaccines containing aluminum (as adjuvant) are given to infants, but thimerosal (as preservative) is found mostly in vaccines used in non-industrialized countries. Exclusively, breastfed infants (in Brazil) receiving a full recommended schedule of immunizations showed an exceedingly high exposure of Al (225 to 1750 µg per dose) when compared with estimated levels absorbed from breast milk (2.0 µg). This study does not dispute the safety of vaccines but reinforces the need to study long-term effects of early exposure to neuro-toxic substances on the developing brain. Pragmatic vaccine safety needs to embrace conventional toxicology, addressing especial characteristics of unborn fetuses, neonates and infants exposed to low levels of aluminum, and ethylmercury traditionally considered innocuous to the central nervous system.

Trace determination of free formaldehyde in DTP and DT vaccines and diphtheria-tetanus antigen by single drop microextraction and gas chromatography-mass spectrometry.

An immersed single drop microextraction (SDME) method was successfully developed for the trace enrichment of formaldehyde from DTP and DT vaccines and diphtheria-tetanus antigen. The formaldehyde was derivatized by means of the Hantzsch reaction. The dehydropyridine derivative was extracted into a microdrop of chloroform that suspended in a 4 ml sample solution for a preset time. The microdrop was then retracted into the microsyringe and injected directly into a gas chromatography-mass spectrometry (GC-MS) injection port. Effects of different parameters such as the type of solvent, extraction time, stirring rate, and temperature were studied and optimized. The limit of detection was 0.22 ng/l and relative standard deviation (RSD) value was 6.2% (n=5). The regression coefficient was satisfactory (r(2)=0.992) and linear range was obtained from 1 to 500 ng/l.

[Effect on anti-pertussis antibodies of reducing the amount of Japanese Diphteria-Pertussis-Tetanus vaccine among adults].

The wide spread use of Diphteria-Pertussis-Tetanus (DPT) vaccination has made pertussis rare among infants, but reports have noted the rise in adult pertussis in the United States and in Japan. Adult pertussis vaccination in the US has been approved and is becoming widely disseminated, but not in Japan, where only way to prevent adult pertussis is vaccination using infantile DPT vaccine. Reducing the Japanese DPT vaccine dose to 0.2 mL in the hope of minimizing adverse events, we studied its efficacy and safety. We nearly equalized diphteria and tetanus antigenic titers to a 0.1 mL dose of diphteria-tetanus bivalent vaccine--the booster dose regularly used in Japan--containing anti-FHA antibody titers similar to effective pertussis vaccines approved in the US. Subjects were 30 healthy volunteers who gave oral and written consent, testing anti-PT and anti-FHA antibody titers 4 weeks after vaccination. Of the 30, 29 showed a titer increase. Anti-tetanus toxoid titers tested showed increased titers in 28 subjects, the remaining 2 assumed to not have undergone previous tetanus vaccination. The incidence of local adverse effects was higher in adults than in children, but none were serious. A Japanese DPT vaccine dose of 0.2 mL thus proved effective against pertussis in adults.

Vacunación frente a la Tos ferina / No disponible

No disponible

Vacunación frente a la tos ferina en el adolescente y el adulto / Whooping cough vaccination in adolescents and adults

La tos ferina continúa siendo un problema importante desalud pública, a pesar de que se dispone de vacunaseficaces desde hace más de 50 años. En los últimos añosse ha observado un resurgimiento de esta infección enalgunos países, incluso en los que disponen de coberturasvacunales elevadas, que se asocia con un aumento decasos en adolescentes y adultos. Este incremento seexplica por la disminución de la inmunidad vacunal ynatural con el paso del tiempo, y por el descenso de laincidencia de la enfermedad debido a las campañas devacunación, lo que ha producido una disminución delefecto booster inducido por la infección natural. Lasvacunas antipertusis confieren una inmunidad de cortaduración; a los 4 años de la última dosis, la eficacia vacunales del 84% y disminuye hasta el 46% a los 7 años. Portanto, si se considera que en la mayoría de los países laúltima dosis de vacuna DTP se administra a los 4-6 años de edad, es previsible que, si no hay una exposición natural a Bordetella pertussis, sólo la mitad de los inmunizados estarán protegidos al llegar a la adolescencia, y el número de personas susceptibles aumentará con la edad.La reciente comercialización de vacunas acelulares concomponente antigénico reducido, para uso enadolescentes y adultos (dTpa), va a permitir un mejorcontrol de esta infección. La vacunación universal de losadolescentes es ya una realidad en algunos países. Lasestrategias de vacunación del adulto son más difíciles deimplementar, aunque hay un amplio consenso en losgrupos de riesgo prioritarios

Whooping cough continues to be a major public healthproblem, even though effective vaccines have beenavailable for more than 50 years. In the last few years,there has been a re-emergence of this infection in somecountries, even in those with high vaccination coverage,associated with an increase in cases in adolescents andadults. This increase is explained by the decrease innatural and vaccine immunity with the passage of timeand by the reduction in the incidence of this disease due tovaccination campaigns, which have reduced the boostereffect induced by natural infection. Pertussis vaccinesconfer short-term immunity; 4 years after the last dose,vaccine efficacy is 84%, decreasing to 46% after 7 years.Therefore, since the last dose of the diphtheria-tetanuspertussis(DTP) vaccine is administered at the age of 4-6years in most countries, if there is no natural exposure to Bordetella pertussis, only half of the vaccinated individuals will be protected on reaching adolescence, and the number of susceptible individuals will increase with age.The recent entry on to the market of acellular vaccineswith a reduced antigenic component for use in adolescentsand adults (DTaP), will allow better control of thisinfection. Universal vaccination of adolescents is already being carried out in many countries. Vaccination strategies in adults are more difficult to implement, although there is wide consensus in priority risk groups

Vacunas combinadas / Combined vaccines

Las vacunas combinadas son las que contienen antígenosque pertenecen a 2 o más microorganismos; se conocenhace ya 60 años, desde que en 1948 se autorizó la vacunaDTP. La disponibilidad de vacunas combinadas facilitaaumentar el número de antígenos en los calendarios deinmunizaciones sistemáticas, con un menor número deinyecciones y una mayor aceptación por parte del personalsanitario y de la población, y permite obtener mejorescoberturas vacunales. A pesar del importante aumento delnúmero de vacunas sistemáticas administradas a los niños(en los últimos 100 años se ha pasado de 1 a 14 vacunas),la cantidad de componentes antigénicos no sólo no haaumentado, sino que ha disminuido (de 200 en 1903, a 130en 2007), al obtenerse vacunas cada vez más purificadas.El aumento creciente del número de vacunas en loscalendarios de inmunizaciones en los últimos años hahecho progresar la investigación y el desarrollo de vacunas combinadas. A partir de la vacuna trivalente DTP, en las formas DTPe y DTPa, se han desarrollado 2 grupos de vacunas combinadas, y en la actualidad se dispone de tetravalentes, pentavalentes y una hexavalente con DTPa.Hay un tercer grupo de vacunas combinadas en cuyacomposición no está la vacuna DTP. Finalmente, hay quedestacar una vacuna heptavalente, en la que se añade auna de las pentavalentes (DTPe-HB-Hib) las vacunasconjugadas para el meningococo A y C; esta vacuna se hapresentado en marzo de 2007 a la Agencia Europea deMedicamentos para los países del «cinturón de lameningitis»

Combined vaccines contain antigens belonging to two ormore microorganisms; these vaccines have existed for thelast 60 years, ever since the diphtheria-tetanus-pertussis(DTP) vaccine was authorized in 1948. The availability of combined vaccines helps to increase the number of antigens in immunization schedules, with a lower number of injections and greater acceptance by health workers and the general population. Furthermore, these vaccines improve vaccination coverage. Despite the substantial increase in the number of systematic vaccinesadministered to children (increasing in the last 100 years from 1 to 14 vaccines), the quantity of antigeniccomponents has not only not increased but has actuallydecreased (from 200 and 1903 to 130 in 2007) due to theavailability of increasingly purified vaccines. The upward trend in the number of vaccine immunization schedules in the last few years has stimulated research and development into combined vaccines. Based on thetrivalent DTP vaccine, either whole-cell DTP or DTaP, twogroups of combined vaccines have been developed andtetravalent, pentavalent and hexavalent forms arecurrently available with DTPa. There is a third group ofcombined vaccines that does not contain the DTP vaccine.Finally, there is a heptavalent vaccine in which theconjugate vaccines for meningococcus A and C are addedto one of the pentavalent vaccines (whole cell DTP-HBHib); this vaccine was presented in March 2007 to theEuropean Medicines Agency for countries in the meningitisbelt

Unexpectedly high incidence of persistent itching nodules and delayed hypersensitivity to aluminium in children after the use of adsorbed vaccines from a single manufacturer.

During trials of aluminium adsorbed diphtheria-tetanus/acellular pertussis vaccines from a single producer, persistent itching nodules at the vaccination site were observed in an unexpectedly high frequency. The afflicted children were followed in a longitudinal observational study, and the presence of aluminium sensitization was investigated in the children with itching nodules and their symptomless siblings by patch tests. Itching nodules were found in 645 children out of about 76,000 vaccinees (0.8%) after both subcutaneous (s.c.) and intramuscular (i.m.) injection. The itching was intense and long-lasting. So far, 75% still have symptoms after a median duration of 4 years. Contact hypersensitivity to aluminium was demonstrated in 77% of the children with itching nodules and in 8% of the symptomless siblings who had received the same vaccines (P<0.001). Children with persistent itching nodules and/or aluminium sensitization should be warned about aluminium containing products (e.g. vaccines and antiperspirants). The reason for the high incidence of itching nodules after SSI vaccines is unknown and should be further investigated.

Vitamin A as adjuvant to the mouse immune response to pertussis, tetanus and diphtheria vaccines

Vitamin A was used as adjuvant, comparatively with Al(OH)3, in pertussis, tetanus and diphtheria vaccines. Both groups induced a primary immune response in mice, and one single booster dose elevated the antibodies titers in average 554 times to vitamin A groups and 104 times to Al(OH)3. These antibodies titers correlate with sera IL-4 in immunized animals, suggesting a Th2 response. Other cytokines detected in the sera and/or lymphocytes culture supernatants (IL-2 and IFN- ) indicated that vitamin A could also modulate a Th1 response in DPT and acellular pertussis vaccines.

Vacunas combinadas: pentavalentes y hexavalentes. Introducción en la vacunación infantil / Vaccines combined: pentavalents and hexavalents. Incorporation in the primary vaccination on infants

La incorporación de mayor número de vacunas en los calendarios infantiles ha abierto nuevas vías de investigación. Este trabajo consiste en hacer una revisión bibliográfica sobre las vacunas combinadas con la intención de analizar su evolución y especialmente la inmunogenicidad, seguridad de las vacunas pentavalentes y hexavalentes. Las vacunas pentavalentes y hexavalentes parecen ser seguras y no se han comunicado reacciones adversas de relevancia clínica. Ambas llegan a parámetros subrogados de protección. Queda por definir más concretamente la duración del efecto protector así como establecer la eficacia y efectividad vacunal. Por el momento sólo existen estudios en Fase III, donde demuestran su aceptable inmunogenicidad, reactogenicidad, mayor aceptabilidad al reducir el número de inyecciones y menores costes de almacenamiento, tiempo de administración y material utilizado. Por todo ello hace posible su futura inclusión de forma sistemática en el calendario vacunal. (AU)

Quantitative determination of saccharide in Haemophilus influenzae type b glycoconjugate vaccines, alone and in combination with DPT, by use of high-performance anion-exchange chromatography with pulsed amperometric detection.

The stability and integrity of glycoconjugate vaccines requires determination of the total saccharide and quantification of the unbound or free saccharide present. The traditional assay for Hib conjugates, based on colorimetric determination of ribose, has been much improved by the use of base hydrolysis and analysis of the Hib subunit generated using high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD). The production of this subunit was confirmed by NMR analysis. However, quantification of free Hib saccharide using this method was not possible in the combination vaccines evaluated due to interferences emanating from DPT. Thus a method based on TFA hydrolysis followed by the chromatographic separation and quantification of ribitol on a CarboPac MA1 column was developed. The method is selective, and with the use of ED40 electrode, requires only nanomole amounts for the chromatographic step, thereby ensuring that free saccharide can be monitored accurately in the formulated Hib-CRM vaccine alone and when in combination with other vaccines.

Evaluación y mejoramiento del aspecto físico de las vacunas pertussis y DPT elaboradas en el Instituto Nacional de Higiene "Rafael Rangel" / Improvement and evaluation of physical appearance of the pertussis vaccines and DPT elaborates in the Instituto Nacional de Higiene \"Rafael Rangel\"

Se evaluaron los procesos de recuperación de la vacuna pertussis y formulación de la vacuna DPT, elaborados en el Instituto Nacional de Higiene "Rafael Rangel", con el fin de mejorar el aspecto físico u homogeneidad de la vacuna pertussis antes de ser incorporada como fracción en la vacuna DPT. Se evaluaron la calidad del agua, concentración del adyuvante y la concentración y tiempo de almacenamiento de la vacuna pertussis. Se demostró que cuando fueron mezclados lotes de vacunas pertussis de baja concentración (menor de 200 Uop/ml), los cuales habían sido almacenados durante un período menor de dos años y habían sido previamente agitados, con calidad inyectable y a una concentración del adyuvante de 0,52 mg/dosis, generaron una vacuna DPT homogénea, comparable con otras vacunas similares producidas por laboratorios de reconocida trayectoria. Vacunas pertussis concentradas a valores superiores, generaron una vacuna DPT con presencia de aglomerados consistentes de la bacteria Bordetella pertussis. El incremento de la concentración del adyuvante en la vacuna DPT, hasta valores permisibles por la Organización Mundial de la Salud (1,25 mg/dosis) y el uso de agua de calidad inyectable mejoran el aspecto físico de la vacuna DPT. La visualización macroscópica y microscópica de las vacunas

Validation of the toxin-binding inhibition (ToBI) test for the estimation of the potency of the tetanus toxoïd component in vaccines.

A validation study has been performed to determine the suitability of the toxin binding inhibition (ToBI) test for the serological estimation of the potency of the tetanus toxoïd component in vaccines. 37 Murine serum pools over a wide range of antibody levels were titrated in both toxin neutralization (TN) and ToBI test. A good correlation was found between both assays. Sixteen DPT-polio, twelve DT-polio and seven T vaccines were tested in the mouse lethal challenge test and the in vitro serological test, using the ToBI test for determining vaccine-induced tetanus antibodies. For all three types of vaccine a statistically valid correlation between both assays was found. However, for two batches of DPT-polio vaccine an "overestimation" of the tetanus potency was observed in the serological assay compared to the challenge assay. This phenomenon could not be explained by the difference in immunization period nor by misinterpretation of the ToBI test of DPT-polio-induced antibodies. In the LPF test high LPF activity was observed for the deviating DPT-polio vaccines. Therefore, the effect of pertussis toxin (PT) on the potency of the tetanus component in the serological assay was examined. The addition of 2 micrograms of PT to a "normal" DPT-polio vaccine resulted in a nearly twofold increase of the tetanus potency. It was concluded that pertussis toxin has a vaccine dose-dependent adjuvant effect on the potency of tetanus toxoïd resulting in high potency values when determined by ToBI procedure. It is unclear how these findings should be interpreted with respect to the behaviour of such vaccines in man.

Use of in vitro Vero cell assay and ELISA in the United States potency test of vaccines containing adsorbed diphtheria and tetanus toxoids.

Current United States (US) regulations for potency testing of vaccines containing adsorbed diphtheria and tetanus toxoids require in vivo toxin neutralization (TN) tests on the pooled sera of immunized guinea pigs. To reduce the number of animals required for testing, two in vitro tests have been evaluated, the Vero cell assay for diphtheria antitoxin and ELISA for IgG antibody to tetanus toxin; these have been correlated with in vivo TN tests. In the Vero cell method, diphtheria antitoxin titres of the guinea pig sera, obtained four weeks after immunization as per US potency requirements, were markedly dependent on the toxin dose level used in the assay. A toxin dose level termed the Lcd/1 dose (limit of cytopathic dose at a IU/ml) for Vero cells gave comparable estimates of antitoxin activity to the in vivo TN test performed at L+/1 dose of toxin. When lower dose levels of toxin were used in the Vero cells (Lcd/10 to Lcd/1000), diphtheria antitoxin levels in four weeks guinea pig sera were two to 11.7 times lower than with the Lcd/1 dose level. The most likely reason for these differences is that guinea pig sera a 4 weeks are of lower avidity than the equine antitoxin standard. Antibodies of low avidity bind antigen less well at low reactant concentrations. Therefore, to obtain similar estimates of diphtheria antitoxin in the Vero cell method and in vivo TN test, the use of toxin dose for the Vero cell method similar to that for the in vivo TN test is suggested. Another alternative, in which any dose of toxin may be used for the Vero cell method, is the use of a reference guinea pig serum (calibrated in IU/ml by the in vivo TN test at L+/1 level of toxin) that has similar avidity or similar immunization status as the test sera (i.e. 4 week serum). IgG antibodies to tetanus toxin in guinea pig sera were found early in the course of immunization when tetanus antitoxin could not be detected by TN test. Tetanus toxin IgG antibody levels of guinea pig sera calculated in IU/ml against an ELISA guinea pig reference serum (calibrated in IU/ml by TN test) depended upon the immunization status of the animals. To obtain similar estimates of tetanus antibodies in IU/ml by TN and ELISA, the ELISA reference guinea pig serum should have similar immunization status (and presumably similar avidity) as the test serum (i.e. six week serum). We propose that the Vero cell method and ELISA deserve further evaluation to determine whether they can replace in vivo TN tests for titration of diphtheria and tetanus antitoxins in the US potency test.

Vero cell assay validation of an alternative to the Ph. Eur. diphtheria potency tests.

In the framework of the Biological Standardisation Programme of the European Pharmacopoeia Commission, in 1993 a collaborative study was organised for the validation of an alternative to the diphtheria in vivo challenge tests required by the Ph.Eur. monograph V.2.2.7. The alternative assay is based on the detection of neutralising antibodies in the sera from mice immunised with the vaccines to be tested (Vero cell assay). In the study this assay method was validated against intradermal and lethal challenge in guinea-pigs, performed in conformity with Ph.Eur. Therefore the potency currently on the European market, was assayed in parallel by the different assay methods. Seventeen laboratories, from eleven different countries, participated in the study. Three laboratories performed the intradermal challenge assay, while three other laboratories performed the lethal challenge assay. All seventeen laboratories performed the Vero cell assay. The results of the study suggest that the potency of the diphtheria component of both monovalent diphtheria vaccines and combined diphtheria-tetanus vaccines can be estimated adequately by means of the Vero cell assay. It does not yet seem possible for all combined diphtheria-tetanus-pertussis vaccines to replace a potency assay based on the protective capacity of a vaccine in guinea-pigs by the Vero cell assay. This may be due to an adjuvant effect of the pertussis component of the vaccine, in combination with the adsorbent used, which may be more pronounced in mice than in guinea-pigs and may also differ between different strains of mice.

Comparison of in vivo and in vitro methods for determining unitage of diphtheria antitoxin in adsorbed diphtheria-tetanus (DT) and diphtheria-tetanus-pertussis (DTP) vaccines.

In view of the current efforts to find a reliable in vitro method which can suitably act as an alternative for determining the potency of the diphtheria component in a combined vaccine, we have analysed experimental batches by the method proposed by WHO [1] i.e. challenge method in guinea pigs. The same batches were also analysed by the alternative antibody induction method as suggested in the Indian Pharmacopoeia (I.P.) [2] which is similar to the old method suggested in the British Pharmacopoeia (B.P.) 1973. As per I.P. the initial part of raising the antibodies remains unaltered but the actual titration of diphtheria antitoxin from the immunised guinea pigs was performed by using the following in vitro methods: a) indirect haemagglutination test using human "O" red blood cells to coat diphtheria toxoid using chromic chloride as the coupling agent [3]; b) toxin neutralisation test using Vero cells [4]; c) a double diffusion technique in agar gel for titration of diphtheria antitoxin [5]. Our findings show clearly that the results of two in vivo methods i.e. Challenge Test, Alternative I.P. Method and the above-mentioned three in vitro methods are comparable and would certainly reduce the number of animals required by making a combination of in vivo and in vitro techniques to give us an assessment of the potency of the vaccine to be tested.

Comparative studies of the in vivo toxin neutralization and the in vitro Vero cell assay methods for use in potency testing of diphtheria component in combined vaccines/toxoids. 1: Standardization of a modified Vero cell assay for toxin-antitoxin titration of immunized guinea-pig sera.

The in vivo Toxin Neutralization (TN) test is currently used as an antibody limit test for regulatory control testing of diphtheria potency in combined vaccines/toxoids. This test requires the use of guinea-pigs for estimating diphtheria antitoxin titre in immunized sera. The acceptability criteria (minimum requirement) for adsorbed pediatric vaccines/toxoids in the TN test are the production of at least 2.0 IU/ml of antitoxin in the serum pool of immunized animals. The feasibility of employing the in vitro Vero cell assay as an alternative limit test to the TN test was investigated. Parallel titration of serum samples from guinea-pigs immunized with DPT (ads) vaccine (pediatric use) showed that although the in vitro antitoxin titre paralleled the in vivo values, a direct correlation between the two methods could not be established. The mean in vitro titres were lower (in terms of IU/ml) than those obtained by the in vivo TN test. This could possibly be explained by the differences between reference serum which is a hyperimmune horse serum and the test sera which are from guinea-pigs which have been immunized only once. The in vitro/in vivo ratio of the antitoxin titre ranged from 0.1 to 0.24 IU/ml with a mean value of 0.17 (SD, 0.06). Hence, for pediatric vaccines, a tentative in vitro limit of 0.3 IU/ml, which would correspond to the currently required limit of 2.0 IU/ml in the in vivo TN test, could be accepted as the minimum requirement for the antitoxin titre in the Vero cell assay.

Vacunación contra difteria, tosferina y tétanos / Vaccines against diphtheria, whooping cough and tetanus

La difteria, la tosferina o pertusis y el tétanos son tres importantes problemas de salud pública que tienen en común que pueden ser específicamente prevenidas con el uso de una sola preparación vacunal, conocida como vacuna triple bacteriana o DPT (difteria, pertusis y tétanos). La vacuna DPT es una preparación combinada que contiene los toxoides diftérico, tetánico y la vacuna pertusis adsorbidos a un adyuvante, generalmente hidróxido o fosfato de aluminio, ambos de calidad para uso por vía parenteral. Este biológico y las vacunas BCG (bacilo de Calmette y Guérin), toxoide tetánico, antisarampión y antipoliomielítica forman el grupo de las vacunas recomendadas en el Programa Ampliado de Inmunizaciones (PAI) que la Organización Mundial de la Salud ha recomendado para ser aplicado a toda la población mundial menor de 5 años. En México, esta actividad recibe el nombre de Programa Nacional de Inmunizaciones, con la enorme ventaja de que es el único de América Latina que tiene la capacidad de elaborar las vacunas correspondientes. En este capítulo se hará una breve descripción de las tres enfermedades, los agentes etiológicos, los procedimientos de producción de los componentes de la vacuna y sus perspectivas de desarrollo, así como de otras combinaciones de los componentes vacunales

Safety and immunogenicity of acellular pertussis vaccine, combined with diphtheria and tetanus as the Japanese commercial Takeda vaccine, compared with the Takeda acellular pertussis component combined with Lederle's diphtheria and tetanus toxoids in two-, four- and six-month-old infants.

A double blind, randomized, controlled trial compared the safety and immunogenicity of an acellular pertussis vaccine formulated at Lederle using the Takeda acellular pertussis component combined with Lederle diphtheria and tetanus toxoids vaccines (APDT), with the commercially available Japanese Takeda vaccine (APDT-T/J) as a three-dose series to 2-, 4-, and 6-month-old children. Sera were analyzed for antibody to pertussis antigens: lymphocytosis-promoting factor; filamentous hemagglutinin; 69-kDa outer membrane protein; pertussis agglutinogens; neutralizing antibodies to LPF; and to diphtheria and tetanus toxoids. Information concerning local reactions and systemic events were collected daily for 10 days postimmunization. The overall reaction rate was low for both groups. There were no reactions that contraindicated subsequent vaccine and no serious adverse events. For local reactions statistically significant differences between the groups were seen only for a greater incidence of induration in the APDT group at 2 months (12% vs. 0%, P < 0.01), and at 4 months (8% vs. 0%, P = 0.4) compared to the APDT-T/J group. Of the few systemic reactions the only statistically significant difference between the vaccine groups was a greater incidence of fretfulness in the APDT group after the initial immunization (12% vs. 2%, P = 0.05). There were no statistically significant differences in the immune response between the two vaccines at the 7-month visit. We conclude that APDT is equivalent to the commercially available Takeda vaccine (APDT-T/J).