Phase I clinical evaluation of a synthetic oligosaccharide-protein conjugate vaccine against Haemophilus influenzae type b in human adult volunteers.

Since 1989, we have been involved in the development of a vaccine against Haemophilus influenzae type b. The new vaccine is based on the conjugation of synthetic oligosaccharides to tetanus toxoid. Our main goals have been (i) to verify the feasibility of using the synthetic antigen and (ii) to search for new production alternatives for this important infant vaccine. Overall, eight trials have already been conducted with adults, children (4 to 5 years old), and infants. We have described herein the details from the first two phase I clinical trials conducted with human adult volunteers under double blind, randomized conditions. The participants each received a single intramuscular injection to evaluate safety and initial immunogenicity. We have found an excellent safety profile and an antibody response similar to the one observed for the control vaccine.

Phase I Clinical Evaluation of a Synthetic Oligosaccharide-Protein Conjugate Vaccine against Haemophilus influenzae Type b in Human Adult Volunteers

Since 1989, we have been involved in the development of a vaccine against Haemophilus influenzae type b. The new vaccine is based on the conjugation of synthetic oligosaccharides to tetanus toxoid. Our main goals have been (i) to verify the feasibility of using the synthetic antigen and (ii) to search for new production alternatives for this important infant vaccine. Overall, eight trials have already been conducted with adults, children (4 to 5 years old), and infants. We have described herein the details from the first two phase I clinical trials conducted with human adult volunteers under double blind, randomized conditions. The participants each received a single intramuscular injection to evaluate safety and initial immunogenicity. We have found an excellent safety profile and an antibody response similar to the one observed for the control vaccine(AU)

Desde 1989, hemos participado en el desarrollo de una vacuna contra el Haemophilus influenzae tipo b. La nueva vacuna se basa en la conjugación de oligosacáridos sintéticos a toxoide tetánico. Nuestros principales objetivos han sido (i) para verificar la viabilidad de la utilización de la síntesis de antígenos y (ii) búsqueda de nuevas alternativas de producción para este importante vacuna infantil. En total, ocho ensayos ya se han realizado con adultos, niños (de 4 a 5 años), y los lactantes. Hemos descrito en este documento los detalles de los dos primeros ensayos clínicos de fase I realizado con voluntarios adultos humanos en virtud de doble ciego, randomizado condiciones. Los participantes recibieron una única inyección intramuscular para evaluar la seguridad y la inmunogenicidad inicial. Hemos encontrado un excelente perfil de seguridad y una respuesta de anticuerpos similar a la observada para el control de vacunas

Antigenicity and Immunogenicity of a Synthetic Oligosaccharide-Protein Conjugate Vaccine against Haemophilus influenzae Type b

Polysaccharide-protein conjugates as vaccines have proven to be very effective in preventing Haemophilus influenzae type b infections in industrialized countries. However, cost-effective technologies need to be developed for increasing the availability of anti-H. influenzae type b vaccines in countries from the developing world. Consequently, vaccine production with partially synthetic antigens is a desirable goal for many reasons. They may be rigidly controlled for purity and effectiveness while at the same time being cheap enough that they may be made universally available. We describe here the antigenicity and immunogenicity of several H. influenzae type b synthetic oligosaccharide-protein conjugates in laboratory animals. The serum of H. influenzae type b-immunized animals recognized our synthetic H. influenzae type b antigens to the same extent as the native bacterial capsular polysaccharide. Compared to the anti-H. influenzae type b vaccine employed, these synthetic versions induced similar antibody response patterns in terms of titer, specificity, and functional capacity. The further development of synthetic vaccines will meet urgent needs in the less prosperous parts of the world and remains our major goal(AU)

Conjugados proteína-polisacárido como vacunas han demostrado ser muy eficaz en la prevención de Haemophilus influenzae tipo b infecciones en los países industrializados. Sin embargo, tecnologías rentables necesitan ser desarrolladas para incrementar la disponibilidad de anti-H. influenzae tipo b, las vacunas en los países del mundo en desarrollo. En consecuencia, la producción de vacunas con antígenos sintéticos en parte es un objetivo deseable por muchas razones. Pueden ser rígidamente controlada por la pureza y la eficacia al mismo tiempo ser lo suficientemente baratas para que sean universalmente disponibles. Se describe aquí la antigenicidad e inmunogenicidad de varias H. influenzae tipo b-oligosacáridos sintéticos conjugados proteína en animales de laboratorio. El suero de H. influenzae tipo b-reconocido nuestros animales inmunizados sintéticas H. influenzae tipo b antígenos en la misma medida que los nativos bacteriana polisacárido capsular. En comparación con el anti-H. influenzae tipo b vacuna empleada, estas versiones sintéticas similares respuesta de anticuerpos inducida por los patrones en términos de títulos, la especificidad y la capacidad funcional. El ulterior desarrollo de vacunas sintéticas satisfacer las necesidades urgentes en las regiones menos prósperas del mundo y sigue siendo nuestro principal objetivo

Antigenicity and immunogenicity of a synthetic oligosaccharide-protein conjugate vaccine against Haemophilus influenzae type b.

Polysaccharide-protein conjugates as vaccines have proven to be very effective in preventing Haemophilus influenzae type b infections in industrialized countries. However, cost-effective technologies need to be developed for increasing the availability of anti-H. influenzae type b vaccines in countries from the developing world. Consequently, vaccine production with partially synthetic antigens is a desirable goal for many reasons. They may be rigidly controlled for purity and effectiveness while at the same time being cheap enough that they may be made universally available. We describe here the antigenicity and immunogenicity of several H. influenzae type b synthetic oligosaccharide-protein conjugates in laboratory animals. The serum of H. influenzae type b-immunized animals recognized our synthetic H. influenzae type b antigens to the same extent as the native bacterial capsular polysaccharide. Compared to the anti-H. influenzae type b vaccine employed, these synthetic versions induced similar antibody response patterns in terms of titer, specificity, and functional capacity. The further development of synthetic vaccines will meet urgent needs in the less prosperous parts of the world and remains our major goal.

A synthetic conjugate polysaccharide vaccine against Haemophilus influenzae type b.

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.

Maxillary sinus augmentation with deproteinated bovine bone and platelet rich plasma with simultaneous insertion of endosseous implants.

PURPOSE: To investigate the clinical applicability of using deproteinated bovine bone mixed with autologous platelet rich plasma (PRP) in human maxillary sinus augmentations in severely resorbed posterior maxillary alveolar processes with simultaneous insertion of endosseous dental implants. MATERIALS AND METHODS: Fifteen patients with less than 5 mm of residual alveolar bone height in the posterior maxillary alveolus underwent a total of 24 maxillary sinus augmentations. Seventy endosseous implants were inserted simultaneously in the grafted sinuses. The implants were uncovered and loaded 4 months after insertion and the sinus augmentation. An osseous biopsy specimen was obtained from the augmented maxillary sinus in 1 patient. In 3 patients, computed tomography scans of the grafted maxillae were obtained and the bone density quantified and compared with native bone density using SIMPlant 7 (Columbia Scientific, Columbia, MD) software 4 months postoperatively. RESULTS: Although a total of 5 implants in 4 patients were lost, this did not result in the loss of any of the restorations, for an overall success rate of 92.9 %. Follow-up for patients in this study after insertion of the permanent restoration was between 6 and 36 months. The bone biopsy from the patients showed evidence of viable new bone formation in close approximation to the xenograft. The bone density of the grafted bone was similar or exceeded the bone density of the surrounding native maxillary bone. CONCLUSION: Based on our clinical experience, we believe that the use of platelet rich plasma in combination with deproteinated bovine bone is effective for maxillary sinus augmentation with simultaneous insertion of endosseous dental implants in severely resorbed posterior maxillae.