Immune interaction between components of acellular pertussis-diphtheria-tetanus (DTaP) vaccine and Haemophilus influenzae b (Hib) conjugate vaccine in a rat model.

We have previously shown that, consistent with clinical trial results, the immune response to a Haemophilus influenzae b (Hib) conjugate vaccine in a rat model was compromised and modulated when given combined with a DTaP3 vaccine, as compared to both vaccines given separately. The present study extended our investigation to evaluate the immunogenicity of all DTaP3 components in combined versus separate administration of Hib with DTaP3 and investigated immune interactions between Hib and individual components of DTaP3. Rats were immunised with Hib and DTaP3 or with Hib and individual DTaP3 components. Cellular and humoral immune responses to Hib and DTaP3 components were evaluated. Our results indicate that the immunogenicity of DTaP3 components was similar or greater in combined versus separate administration of Hib and DTaP3. Moreover, combined administration of Hib and TT reduced immunogenicity of both Hib and TT. Hib immunogenicity was also significantly reduced when given combined with FHA and following adsorption to Al(OH)3.

Childhood and malaria vaccines combined in biodegradable microspheres produce immunity with synergistic interactions.

Biodegradable microspheres may represent a potential tool for the delivery of combination vaccines. We demonstrate strong immunogenicity of five co-encapsulated antigens after a single subcutaneous inoculation in guinea pigs. Tetanus- and diphtheria-specific antibodies were not significantly affected by the presence of either antigen or by the presence of pertussis or Haemophilus influenzae type b (Hib) antigens. Microsphere formulations gave better protection against diphtheria toxin than did two injections of a licensed tetravalent vaccine. Finally, a synthetic malaria peptide antigen (PfCS) also encapsulated in PLGA microspheres increased diphtheria and tetanus-specific immunity and improved protection against diphtheria. These findings demonstrate the potential of microspheres as an alternative and promising strategy for combination vaccines with a further aptitude in reducing the number of inoculations required to gain functional immunity.

European union regulatory developments for new vaccine adjuvants and delivery systems.

Interest in vaccine adjuvants and new delivery systems has grown rapidly over the past few years. New vaccine candidates have emerged, which, because of their poor immunogenicity, rely on adjuvants to improve their presentation and targeting and to potentiate their protective immune response. Better understandings of the mechanisms of action, together with logistic and economical considerations have resulted in an explosion of technologies. However, there have been few new registered products for human use, and antigens incorporated into immunostimulating reconstituted influenza virosomes have only relatively recently been licensed in European Union (EU) countries. Influenza vaccine, adjuvanted with water in oil emulsion containing squalene (adjuvant MF59C1) is now also approved. Although current EU regulations focus on traditional adjuvants, notably aluminium and calcium salts, advances have been made in regulatory considerations. The European agency for the evaluation of medicinal products, through its working parties, is actively drafting guidance on requirements for the evaluation of new adjuvants in vaccines. This paper summarises the new developments in EU regulatory aspects relevant to adjuvant quality at development stages, during the manufacturing process, and at the final bulk stage of adjuvant with antigen, and also summarises regulatory expectation regarding safety at pre-clinical and clinical stages. The paper highlights the regulatory concerns and existing bottlenecks that have led to slow approval of new technologies.