Characterization and Specification of a Trivalent Protein-Based Pneumococcal Vaccine Formulation Using an Adjuvant-Free Nanogel Nasal Delivery System.

We previously developed a safe and effective nasal vaccine delivery system using a self-assembled nanosized hydrogel (nanogel) made from a cationic cholesteryl pullulan. Here, we generated three pneumococcal surface protein A (PspA) fusion antigens as a universal pneumococcal nasal vaccine and then encapsulated each PspA into a nanogel and mixed the three resulting monovalent formulations into a trivalent nanogel-PspA formulation. First, to characterize the nanogel-PspA formulations, we used native polyacrylamide gel electrophoresis (PAGE) to determine the average number of PspA molecules encapsulated per nanogel molecule. Second, we adopted two methods-a densitometric method based on lithium dodecyl sulfate (LDS)-PAGE and a biologic method involving sandwich enzyme-linked immunosorbent assay (ELISA)-to determine the PspA content in the nanogel formulations. Third, treatment of nanogel-PspA formulations by adding methyl-ß-cyclodextrin released each PspA in its native form, as confirmed through circular dichroism (CD) spectroscopy. However, when nanogel-PspA formulations were heat-treated at 80 °C for 16 h, CD spectroscopy showed that each PspA was released in a denatured form. Fourth, we confirmed that the nanogel-PspA formulations were internalized into nasal mucosa effectively and that each PspA was gradually released from the nanogel in epithelial cells in mice. Fifth, LDS-PAGE densitometry and ELISA both indicated that the amount of trivalent PspA was dramatically decreased in the heat-treated nanogel compared with that before heating. When mice were immunized nasally using the heat-treated formulation, the immunologic activity of each PspA was dramatically reduced compared with that of the untreated formulation; in both cases, the immunologic activity correlated well with the content of each PspA as determined by LDS-PAGE densitometry and ELISA. Finally, we confirmed that the trivalent nanogel-PspA formulation induced equivalent titers of PspA-specific serum IgG and mucosal IgA Abs in immunized mice. These results show that the specification methods we developed effectively characterized our nanogel-based trivalent PspA nasal vaccine formulation.

Kinetics of IgM and IgA antibody response to 23-valent pneumococcal polysaccharide vaccination in healthy subjects.

PURPOSE: A poor antibody response of IgM and IgA antibodies upon vaccination with pneumococcal polysaccharides (PnPS) is discussed as independent risk factors for bronchiectasis in patients with antibody deficiency syndrome (ADS) receiving immunoglobulin replacement therapy. However, the kinetics of the specific IgM and IgA response to vaccination with multivalent pneumococcal polysaccharides requires a more detailed knowledge. In this study we aimed i) to develop a standardised multivalent PnPS-IgM and IgA-ELISA, and ii) to compare the sensitivity of the multivalent to the serotype specific antibody response, and iii) to determine the kinetics of the anti-PnPS IgM and IgA antibodies in healthy subjects. METHODS: We immunised n=20 healthy adults with a 23-valent PnPS vaccine (Pneumovax®). The kinetics of the 23-valent antibody response was assessed for 1 year with newly developed ELISAs for IgM and IgA isotypes, along with serotype specific responses. RESULTS: The IgA and IgM antibody response peaked at 2 and 3 weeks, respectively. IgM antibody levels remained at a plateau (above 80 % of peak response) for 3 months. After one year, specific antibody levels were still at about 30 % of the peak response. The 23-valent antibody response yielded significantly higher responder rates than assessment of single serotypes. CONCLUSION: Testing the IgM and IgA immune response to polysaccharide vaccination with a multivalent PnPS ELISA may be a feasible tool for assessment of the immune function in patient groups who receive IgG replacement therapy.

Vacuna frente al neumococo en pacientes con artritis reumatoide / No disponible

No disponible

Bacteriemia neumocócica durante el año 2009 en un hospital pediátrico de nivel 2: características clínicas y microbiológicas / Bacteremia pneumococcal throughout 2009 in a level 2 children's hospital: clinical and microbiological characteristics

Objetivo: Estudiar las características clínicas y microbiológicas de los pacientes con hemocultivo positivo a Streptococcus pneumoniae durante el año 2009 en un hospital pediátrico de nivel 2. Material y métodos: Estudio observacional descriptivo de los pacientes pediátricos con hemocultivo positivo a neumococo desde el 1 de enero hasta el 31 de diciembre de 2009. Se analizaron las siguientes variables: edad, vacunación antineumocócica conjugada heptavalente, antibioterapia previa, diagnóstico clínico, serotipo y sensibilidad antibiótica, así como la necesidad de ingreso hospitalario. Resultados: Se detectaron 15 pacientes con hemocultivo positivo a S. pneumoniae. El 60% de los aislamientos se obtuvo en niños entre 3 y 36 meses de edad. El diagnóstico clínico más frecuente fue neumonía, con o sin derrame pleural (67%). El serotipo aislado más frecuentemente fue el 1 (40%). Todos los pacientes infectados por el serotipo 1 presentaban como manifestaciónclínica la neumonía. Todas las cepas aisladas fueronsensibles a penicilina y cefotaxima según los nuevos criterios del Clinical Laboratory Standards Institute (2008). El 80%de los serotipos aislados están incluidos en la vacuna antineumocócica conjugada 13-valente, el 67% en la 10-valente y ninguno en la 7-valente.Conclusión: Los serotipos más frecuentemente aislados productores de enfermedad neumocócica invasiva durante el año2009 en nuestro centro son serotipos no incluidos en la vacuna antineumocócica conjugada heptavalente. Todos los serotipos aislados fueron sensibles a penicilina y cefotaxima(AU)

Objective: To study the clinical and microbiological characteristics of patients with positive blood culture for Streptococcus pneumoniae in 2009 in a pediatric level 2 hospital. Material and methods: Retrospective observational study of pediatric patients with positive blood culture for Streptococcus pneumoniae from January 1st to December 31st 2009. We analyzed the following variables: age, heptavalent pneumococcal conjugate vaccine (PCV7), previous antibiotic therapy, clinical diagnosis, serotype and antibiotic sensitivity and need for hospitalization. Results: We identified 15 patients with positive blood culture for S. pneumoniae (60%) and were obtained in children aged between 3 and 36 months of age. The most common clinical diagnosis was pneumonia with or without pleural effusion(67%). Serotype 1 was the most frequently isolated serotype(40%). All serotype 1-infected patients had pneumonia as a clinical manifestation. All isolates were susceptible to penicillin and cefotaxime under the new criteria of the Clinical Laboratory Standards Institute (2008). 80% of the isolated serotypes are included in pneumococcal conjugate vaccine13-valent, 67% in 10-valent and none in 7-valent.Conclusion: The most frequently isolated invasive pneumococcal disease producing serotypes in our center in 2009 were serotypes not included in PCV7 and were sensitive to penicillin and cefotaxime(AU)

Safety, immunogenicity and kinetics of immune response to 7-valent pneumococcal conjugate vaccine in children with idiopathic nephrotic syndrome.

Safety, immunogenicity and kinetics of 7-valent pneumococcal-conjugate vaccine (PCV7) immune response were evaluated in 33 children with idiopathic nephrotic syndrome (INS) and 16 controls. PCV7 was not associated with increased risk of relapse (RR=0.80, p=0.61). Serotype (PS)-specific antibodies increased in all subjects at 1 month (p<0.01) with inferior immunogenicity for 3/7 PS in patients on immunomodulators (p<0.02). Most patients retained protective antibodies at 12-14 months although at lower levels for 4/7 PS (p<0.08). Different PS kinetics in INS suggests antibody monitoring and revaccination when necessary for protection from pneumococcal infections.

Impacto de la vacuna neumocócica conjugada heptavalente en una población con valores bajos-intermedios de vacunación / Impact of 7-valent pneumococcal conjugate vaccination in a population with low to intermediate vaccination levels

Objetivo: Analizar la evolución de los casos declarados (notificación microbiológica) de enfermedad neumocócica invasora (ENI) en niños menores de 2 años de Cataluña (España) después de la comercialización de la vacuna neumocócica conjugada heptavalente. Material y métodos: Los casos de ENI en los niños menores de 2 años se han obtenido a partir de las declaraciones efectuadas al Sistema de Notificación Microbiológica de Cataluña durante los períodos 1997¿1999 y 2002¿2004 por los hospitales (n=23) que han participado de forma continuada e ininterrumpida en este sistema desde su puesta en marcha en 1995. Resultados: Las tasas globales de casos declarados fueron de 49,2 por 100.000 personas-año durante el período 1997¿1999 y de 40,4 por 100.000 personas-año en el período 2002¿2004. La diferencia no fue estadísticamente significativa. Las tasas de neumonías bacteriémicas pasaron de 25,2 por 100.000 personas-año en 1997¿1999 a 21,6 por 100.000 personas-año en 2002¿2004, y las de meningitis de 6,0 a 4,3 por 100.000 personas-año, respectivamente, pero en ambos casos las diferencias no alcanzaron significación estadística (p>0,05). Conclusiones: Después de la comercialización de la vacuna neumocócica conjugada heptavalente, se ha producido una cierta reducción, no estadísticamente significativa, en las tasas de notificaciones de la enfermedad neumocócica invasora en los niños menores de 2 años de Cataluña. En caso de haber alcanzado significación estadística, la reducción global habría sido del 17,90%, no muy lejana de la reducción teóricamente esperada (22%), a partir de la eficacia protectora de la vacuna (89%), el porcentaje de serotipos causantes de enfermedad invasora incluidos en la vacuna (70%) y las coberturas vacunales alcanzadas durante el período analizado (35%) (AU)

Objective: To analyze the changes occurring in declared cases (microbiological report) of invasive pneumococcal disease (IPD) in children <2 years old in Catalonia (Spain) after the 7-valent pneumococcal conjugate vaccine (PCV7) was licensed for use. Material and methodsCases of IPD in children <2 years old were obtained from notifications to the Microbiological Reporting System of Catalonia (MRSC) in 1997¿1999 and 2002¿2004 by the hospitals (n=23) that have participated in the MRSC continuously and uninterruptedly since its inception in 1995. Results: Overall reported rates were 49.2 cases per 100,000 persons-year in 1997¿1999 and 40.4 per 100,000 persons-year in 2002¿2004; the difference was not statistically significant. The rate of bacteremic pneumonia fell from 25.2 per 100,000 persons-year in 1997¿1999 to 21.6 per 100,000 persons-year in 2002¿2004, and meningitis from 6.0 to 4.3 per 100,000 persons-year; again, differences were not statistically significant (P>0.05). Conclusions: After PCV7 was licensed for use, a noticeable, but non-significant, reduction in reported IPD rates in children <2 years old occurred in Catalonia. If the results had been statistically significant, the overall reduction would have been 17.90%, not far below the theoretically expected reduction (22%), based on the protective efficacy of PCV7 (89%), the percentage of invasive disease-causing serotypes included in the vaccine (70%), and the vaccination coverage achieved during the study period (35%) (AU)

Vacuna conjugada neumocócica heptavalente: ¿luces y sombras? / No disponible

La vacuna antineumocócica conjugada heptavalente ha demostrado una alta eficacia, no solo al reducir la frecuencia de enfermedad neumocócica invasiva en niños, sino también en la disminución de resistencias a los antibióticos y de la colonización nasofaríngea, lo que repercute en grupos de más edad. La publicación de trabajos que muestran un aumento de los aislamientos de serotipos no vacunales, principalmente el 19A, aunque con un impacto sobre la enfermedad aún poco importante, arroja sombras en el mencionado panorama de éxito vacunal. Proponemos una revisión de la bibliografía reciente con el objetivo de ofrecer una visión actual tanto de la vacuna, como de las posibles controversias (AU)

The heptavalent pneumococcal conjugate vaccine has proved a high efficacy, not only to reduce the incidence of invasive pneumococcal disease in children, but also in the decrease of resistance to antibiotics and nasopharyngeal colonization, which affects older age groups. The publication of papers that show an increase of isolates of non-vaccine serotypes, mainly 19A, but with an impact on the disease still unimportant, casts shadows in the above picture of success vaccine. We propose a review of recent literature with the aim of providing an overview of both the current vaccine, as well as the potential disputes (AU)

Efecto de la vacuna heptavalente contra Streptococcus pneumoniae en niños con implante coclear / Efficacy of heptavalent pneumococcal conjugate vaccine in children with cochlear implant

Objetivo: Analizar la eficacia de la vacunación conjugada heptavalente contra Streptococcus pneumoniae (VPn7) en niños con implante coclear en la eliminación de portadores nasofaríngeos y la prevención de complicaciones. Análisis de resistencia y sensibilidad a los antimicrobianos de las cepas de neumococos aisladas tanto en portadores nasofaríngeos con implante vacunados como en niños sanos no vacunados. Método: Se estudia el estado de portador nasofaríngeo de neumococo mediante un análisis prospectivo en dos grupos de niños de 1 a 5 años de edad, durante los años 2005 y 2006. Un grupo incluye a 55 niños con implante coclear y vacunados con VPn7, y un segundo grupo está formado por 60 niños sanos sin vacunación. De cada paciente se recogieron muestras nasofaríngeas para la detección de neumococo, sus serotipos y su sensibilidad a antibióticos. Resultados: El análisis del grupo control no vacunado presenta un tasa de portadores de neumococo en faringe del 25 %, mientras que esta cifra disminuye al 11 % en el grupo de niños vacunados. Los serotipos no vacunales (83,3 %) aislados en pacientes vacunados, mostraban sensiblilidad alta o moderada a penicilina. No se han producido complicaciones a causa de infecciones por S. pneumoniae en ninguno de los pacientes implantados y vacunados. Conclusiones: La VPn7 contribuye a la disminución de la colonización faríngea por neumococo en general y, en particular, por los serotipos de neumococo incluidos en la vacuna, aunque se produce un fenómeno de remplazo por serotipos no vacunales

Objective: The aim is to analyze the efficacy of heptavalent conjugate vaccine against Streptococcus pneumoniae (VPn7) in children with cochlear implant, in relation with the eradication of nasopharyngeal carriers and the prevention of complications. Analysis of the antimicrobial resistance and sensitivity of the different pneumococci strains isolated in cochlear implant nasopharyngeal carriers and healthy non-vaccinated children. Method: Pneumococcal nasopharyngeal carriers were analyzed in this prospective study including two groups of children aged between 2 and 5 years, from 2005 to 2006. The first group included 55 cochlear implant recipients and all of them were vaccinated with VPn7. The second group included 60 non-vaccinated healthy children. Nasopharyngeal swabs for culture were obtained from each child in order to detect the pneumococcus, its serotypes and the sensitivity to antibiotics. Results: In the control group of non-vaccinated children, 25 % of them were found to be pharyngeal pneumococcus carriers, whereas this figure fell to 11 % in the vaccinated group. The non-vaccine serotypes (83.3 %) isolated in vaccinated children showed high or moderate sensitivity to penicillin. There were no complications due to S pneumoniae infections in any of the patients with cochlear implant who were vaccinated. Conclusions: VPn7 contributes to a decrease in pharyngeal colonization by pneumococci in general and, in particular, by the pneumococcal serotypes included in the vaccine, although there is a replacement phenomenon involving non-vaccine serotypes

Enfermedad neumocócica invasiva en la población menor de 5 años de edad de Navarra (2000-2005): impacto de la vacuna conjugada / Invasive pneumococcal disease in children younger than 5 years in Navarra, Spain (2000-2005). Impact of the conjugate vaccine

Fundamento y objetivo: Desde junio de 2001 se comercializa en España la vacuna neumocócica conjugada heptavalente (VNC7v). Nuestro objetivo ha sido evaluar su impacto en la incidencia de enfermedad neumocócica invasiva (ENI) en Navarra. Población y método: Los laboratorios de microbiología de Navarra declaran todos los aislamientos de neumococo en muestras de fluidos corporales normalmente estériles. Analizamos la incidencia de ENI en niños menores de 5 años entre las semanas 41 de 2000 y 40 de 2005. Resultados: Las dosis de VNC7v vendidas hasta 2005 permitirían alcanzar una cobertura del 27% en menores de 5 años, suponiendo 4 dosis por niño. Entre las 5 temporadas se diagnosticaron 103 casos de ENI. Comparando la incidencia de ENI en las 2 primeras temporadas (2000-2002) con la última (2004-2005), se observa un descenso del 69% en la tasa por serotipos vacunales (de 33 a 10 casos por 100.000 menores de 5 años; p = 0,003). Entre esos mismos períodos, la incidencia de ENI por serotipos no vacunales aumentó un 36% (de 42 a 57 por 100.000; p = 0,405). La incidencia global de ENI disminuyó un 12% (de 77 a 67 por 100.000; p = 0,689). El porcentaje de casos que habían recibido VNC7v aumentó hasta el 45% en la temporada 2004-2005 (p < 0,001). Las meningitis y neumonías bacteriémicas supusieron el 42% de las ENI, sin cambios significativos durante el período (p = 0,442). Conclusiones: Tras la comercialización de la VNC7v ha cambiado el patrón de serotipos, pero no se ha conseguido el descenso esperado de la incidencia global de ENI

Background and objective: The 7-valent pneumococcal conjugate vaccine (PCV7) has been commercialized in Spain since June 2001. We aim to evaluate the impact of this vaccine in the incidence of invasive pneumococcal disease (IPD) in Navarre. Population and method: The laboratories of microbiology of Navarre declare all the isolations of Streptococcus pneumoniae in samples of normally sterile corporal fluids. We analyzed the incidence of IPD in children younger than 5 years between weeks 41 of 2000 and 40 of 2005. Results: The doses of PCV7 sold up to 2005 would provide a cover of 27% in children younger than 5 years, having assumed 4 dose schedules. In the 5 seasons, 103 cases of IPD were diagnosed. From the 2 first seasons (2000-2002) to the last one (2004-2005) a reduction of 69% in the incidence rate of IPD caused by vaccine serotypes was observed (from 33 to 10 cases by 100,000 children under 5 years; p = 0.003). Between those same periods the incidence of IPD caused by non-vaccine serotypes increased a 36% (from 42 to 57 by 100,000; p = 0.405). The global incidence of IPD diminished a 12% (from 77 to 67 by 100,000; p = 0.689). The percentage of cases that had received PCV7 increased until 45% in season 2004-2005 (p < 0.001). The meningitis and bacteraemic pneumonias supposed 42% of the IPD, without significant changes during the period (p = 0.442). Conclusions: Since the PCV7 was marketed the pattern of serotypes has changed, but the expected reduction in the total IPD incidence has not been achieved

Predictors of pneumococcal vaccination uptake in hospitalized patients aged 65 years and over shortly following the commencement of a publicly funded national pneumococcal vaccination program in Australia.

In January 2005, Australia became the first country to introduce a publicly funded pneumococcal vaccination program for persons 65 years and older which is free at point of service, although the vaccine cost had previously been partially subsidized. Hospitalization in this age group is an important indicator of risk of invasive pneumococcal disease but vaccine uptake has been suboptimal. To determine vaccination rates and predictors of vaccination in the elderly hospitalised patients before and after January 2005. We validated vaccination status against general practitioner (GP) records for patients aged > or = 65 years admitted to a large teaching hospital in Sydney between 16th of May 2005 and the 20th of February 2006 and examined predictors of vaccination. Commencement of the new program resulted in a significant increase in vaccination uptake from 39% of inpatients prior to the free program to 73% in the same cohort of inpatients post January 2005. We found that patient recall of vaccination status was not reliable. Self-report of pneumococcal vaccination had a sensitivity of 0.53 and a specificity of 0.55, highlighting that validation of vaccination status is required. Age over 80 years and dementia significantly predicted under-vaccination. This highlights the importance of integrating free vaccine supply and delivery in primary care to achieve high vaccination coverage. However, demented patients and the very elderly remain under-vaccinated, despite being admitted to hospital for active management of acute conditions.

Vacuna de polisacárido meningocócico del grupo C conjugada con toxoide tetánico. Un meta-análisis de la inmunogenicidad, seguridad y posología / Group C Meningococcal Polysaccharide-Tetanus Toxoid Conjugate Vaccine. A Meta-Analysis of Immunogenicity, Safety and Posology

La vacuna que contiene polisacárido de meningococodel grupo C de-O-acetilado, conjugada con toxoidetetánico (GCMP-TT), se ha autorizado en 32países y se ha incorporado en un programa de vacunaciónrutinaria en el Reino Unido. Rápidamentese ha acumulado una gran experiencia, que es elobjeto de este meta-análisis, sobre la inmunogenicidad,seguridad y posología de GCMP-TT, así comosobre su impacto epidemiológico. GCMP-TT ha demostradoser efectiva tras una dosis única en individuosmayores de 12 meses de edad y su posologíainicial especificaba tres dosis en lactantes. Sin embargo,según un ensayo clínico reciente, la posologíase redujo a dos dosis en lactantes. La tasa deprotección recogida, definida como la proporción deindividuos con títulos de anticuerpos bactericidas ensuero (SBA) ≥1:8, fue del 99,4% (CI, 98.2-99.9%) ensiete estudios clínicos que abarcan todos los gruposde edad. Se han demostrado respuestas fuertes aGCMP-TT con respecto a SBA, niveles de IgG y deavidez a los anticuerpos. En la farmacovigilanciadespués de la comercialización, que abarca >12 x106 GCMP-TT dosis distribuidas por todo el mundo,la vacuna ha sido bien tolerada con una tasa de incidenciade 0,01% para todos los tipos de efectos adversosmás comúnmente encontrados. Después deuna campaña de vacunación general en el ReinoUnido, en la que a los niños de 5-8 años se les dioprimeramente GCMP-TT, se observó una disminucióndel 93% en la incidencia de enfermedad meningocócica.A la vista de esta inmunogenicidad, seguridady adaptación potencial al uso en lactantes enprogramas de posología reducida, la vacuna GCMPTTmarca un mayor avance sobre las vacunas depolisacárido predecesoras en la prevención de enfermedadmeningocócica C

A conjugate vaccine comprised of de-O-acetylatedgroup C meningococcal polysaccharide coupledto tetanus toxoid (GCMP-TT) has been licensed in32 countries and incorporated in a comprehensiveUK vaccination program. Extensive evidence, formingthe subject of this meta-analysis, has rapidlyaccumulated on the immunogenicity, safety and posologyof GCMP-TT as well as its epidemiologicalimpact. GCMP-TT has been shown effective after asingle dose in individuals > 12 months of age, andinitial posology specified three doses in infants. However,based on a recent clinical trial, posology wasreduced to two doses in infants. Pooled protectionrate, defined as proportion of subjects with serumbactericidal antibody (SBA) levels 1:8, was 99.4%(CI, 98.2-99.9%) in 7 clinical trials covering all agegroups. Robust responses to GCMP-TT have been demonstrated with respect to SBA, IgG levels andantibody avidity. In post-marketing pharmacosurveillanceencompassing > 12*106 GCMP-TT doses distributedworldwide, the vaccine has been well toleratedwith an incidence rate of 0.01% for all the mostcommonly encountered types of adverse events. Aftera catch-up UK vaccination campaign where 5-8year old children were primarily given GCMP-TT, a93% decline in meningococcal disease incidencewas observed. In view of its immunogenicity, safetyand potential suitability for use among infants in reduceddose schedules, GCMP-TT appears to marka major advance over predecessor polysaccharidevaccines for the prevention of meningococcal C disease

Estudio EVAN-50: efectividad de la vacuna antineumocócica polisacárida en la prevención de infecciones neumocócicas en población mayor de 50 años / EVAN-50 Study: effectiveness of polysaccharide pneumococcus vaccine in preventing pneumococcal infections in the over-50 population

Objetivo. Evaluar la efectividad de la vacunación antineumocócica 23-valente en la prevención de infecciones neumocócicas graves en población mayor de 50 años. Diseño. Estudio de casos y controles. Emplazamiento. Atención primaria de salud (Región Sanitaria de Tarragona). Participantes. Un total de 270 pacientes >50 años con una enfermedad neumocócica grave (incluidas la enfermedad invasiva y las neumonías neumocócicas no bacteriémicas) y un total de 540 controles seleccionados aleatoriamente en los registros de usuarios de los centros de salud de referencia de los casos (tras aparejamiento por edad, sexo, médico de cabecera y estrato de riesgo para neumonía). Mediciones principales. Como medida del efecto se usará la odds ratio (OR), realizándose un análisis multivariante de regresión logística para el control de los posibles factores de confusión, estimándose unas OR ajustadas y calculándose la efectividad vacunal (EV) mediante la fórmula: EV = 1 ­ OR. Se discriminará la efectividad de la vacuna para los diferentes grupos de edad y en cada uno de los estratos de riesgo. Finalmente, se evaluará también la efectividad vacunal mediante un análisis de cohortes indirectas, considerando como casos los episodios causados por serotipos vacunales y como controles los episodios causados por serotipos no incluidos en la vacuna. Discusión. El estudio podrá dar una respuesta en términos de efectividad de la vacuna para diferentes estratos etarios y de riesgo, y contribuirá a una toma de decisiones respecto al controvertido tema de la indicación sistemática o no de esta vacuna en las personas mayores

Objective. To assess the effectiveness of 23-valent polysaccharide vaccine in preventing severe pneumococcal infections in adults over 50 years old. Design. Case-control study. Setting. Primary Health Care Service, Tarragona, Spain. Patients. A total of 270 patients >50 with severe pneumococcal disease (invasive pneumococcal disease and non-bacteraemic pneumococcal pneumonia) and 540 control patients randomized from the primary care Centres of the case patients. Case and control patients will be matched for age, sex, family physician, and level of risk for pneumonia. Main measurements. Odds ratio (OR) will be used to measure the vaccine effect. Multivariate logistical regression, adjusted for age, sex, and comorbidity, will be conducted. Vaccine effectiveness (VE) will be calculated by the formula, VE=1-OR. Vaccine effectiveness will be distinguished for the various age groups and at each risk stratum. It will also be estimated by means of indirect cohort analysis, taking as cases the infection caused by vaccine serotypes and as controls infection caused by non-vaccine serotype. Discussion. The study will give an answer in terms of effectiveness of the vaccine for several age and risk strata. It will contribute to taking a decision regarding the controversial question of the systematic indication, or otherwise, of this vaccine for the elderly

Complement dependency of splenic localization of pneumococcal polysaccharide and conjugate vaccines.

The immune response to polysaccharides is initiated when polysaccharides bind complement factor C3d, and these polysaccharide-C3d complexes subsequently localize on splenic marginal zone B cells strongly expressing CD21 (complement receptor 2). Infants and children under the age of 2 years have low or absent expression of CD21 on their marginal zone B cells, and consequently do not adequately respond to polysaccharides. In contrast, polysaccharide-protein conjugate vaccines are able to induce antibodies at this young age. Conjugate vaccines apparently overcome the necessity for CD21-C3d interaction for an antipolysaccharide immune response. We demonstrate in a rat model that localization of pneumococcal polysaccharides on splenic marginal zone B cells indeed is complement dependent. We also show that pneumococcal conjugates do not specifically localize on splenic marginal zone B cells and that splenic localization of polysaccharide conjugates is independent of the presence of complement. Thus, the induction of antipolysaccharide antibodies by conjugate vaccines apparently can occur independently of CD21-C3d interaction. These basic findings may explain the effectiveness of conjugated vaccines in young children and may open the way for their application in other patient groups.

Differential regulation of IgG anti-capsular polysaccharide and antiprotein responses to intact Streptococcus pneumoniae in the presence of cognate CD4+ T cell help.

The relative lack of memory for IgG antipolysaccharide responses is believed to be secondary to the inability of polysaccharides to associate with MHC class II molecules and thus a failure to recruit cognate CD4+ T cell help. However, little is known concerning the role of T cells and the generation of memory for antipolysaccharide Ig responses to intact extracellular bacteria. We used heat-killed, intact Streptococcus pneumoniae, capsular type 14 (Pn14), to evaluate the IgM and IgG responses specific for the capsular polysaccharide (PPS14), the phosphorylcholine determinant of the cell wall C-polysaccharide, and the cell wall protein, pneumococcal surface protein A (PspA). We demonstrate that the IgG (but not IgM), anti-PPS14, and anti-PspA responses to Pn14 are CD4+ T cell dependent and TCR specific. Nevertheless, in contrast to the anti-PspA response, the IgG anti-PPS14 response shows no apparent memory, an accelerated kinetics of primary Ig induction, and a more rapid delivery of CD4+ T cell help. In contrast, the IgG anti-phosphorylcholine response, although also dependent on CD4+ T cells, is TCR nonspecific. We make similar observations using soluble conjugates of PPS14-PspA and C-polysaccharide-PspA. These data lead us to suggest that the central issue concerning the mechanisms underlying different functional outcomes for anti-bacterial IgG responses to capsular polysaccharide vs protein Ags is not necessarily based on the ability to recruit cognate CD4+ T cell help, but perhaps on the nature of the B cell Ag receptor signaling that occurs and/or on the responding B cell subpopulations.