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Control testing of combined vaccines: a consideration of potential problems and approaches
1Division of Bacteriology, National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, U.K.
Insights
New combination vaccines offer broader protection but pose challenges. Careful evaluation is crucial to ensure safety and efficacy, as component interactions can affect immunogenicity and stability.
Area of Science:
- Vaccinology and Immunology
- Microbial Pathogenesis and Control
Background:
- Combination vaccines, such as diphtheria, tetanus, pertussis, and Haemophilus influenzae type b (DTP-Hib), are increasingly available.
- Further combinations incorporating inactivated poliovirus, hepatitis B, meningococcal, and pneumococcal components are under development.
- Future combination vaccines may target enteric infections (cholera, typhoid, rotavirus) and other bacterial causes of meningitis and otitis media.
Purpose of the Study:
- To review the development and potential challenges of novel combination vaccines.
- To highlight the complexities in evaluating the safety, immunogenicity, and stability of multi-component vaccines.
Main Methods:
- Review of current and emerging combination vaccine formulations.
- Analysis of potential interactions between vaccine components.
- Discussion of challenges in laboratory control testing and regulatory requirements.
Main Results:
- Component interactions in DTP-Hib vaccines have already indicated potential issues with reactogenicity and immunogenicity.
- Use of carrier proteins like diphtheria and tetanus may lead to excessive antitoxin responses or epitope suppression.
- Competition for adjuvant binding sites can further complicate vaccine performance.
Conclusions:
- The evaluation of combination vaccines requires careful consideration beyond the properties of individual components.
- Potential interactions necessitate rigorous assessment to ensure optimal vaccine performance and safety.
- Future development must address these complexities to successfully implement new combination vaccine strategies.
Abstract:
Vaccines comprising combinations of diphtheria, tetanus and pertussis (DTP) components with Haemophilus influenzae b polysaccharide--protein conjugates (DTP-Hib) are now available. Combinations of DTP-Hib with additional components such as inactivated poliomyelitis vaccine, hepatitis B vaccine, meningococcal and pneumococcal polysaccharide-protein conjugates are under development. Other combinations, such as Hib vaccine with meningococcal A, B and C components and possibly pneumococcal conjugates, or non-capsulated Haemophilus components combined with pneumococcal conjugates, developed against bacterial meningitis and otitis media respectively, are of potential interest. Combination vaccines against enteric infections and including potentially cholera, typhoid, ETEC, Shigella, rotavirus and possibly Campylobacter and Helicobacter components, may become available in the longer term. The control of these combinations is likely to be based on pharmacopoeial requirements for the individual components. However, the evaluation of combinations may not be straightforward and the interaction of the components with each other may influence reactogenicity, immunogenicity and stability and will complicate laboratory control tests. Indications of this have already arisen with some DTP-Hib combinations but are likely to increase as additional components are added. For example, the use of diphtheria and tetanus proteins as carriers for multiple polysaccharide conjugates may lead to excessive antitoxin production and epitope suppression of anti-polysaccharide responses. Other problems may result from competition for binding sites on adjuvant molecules. The requirements for new vaccine combinations need to be considered carefully and should not be made solely on assumptions based on the properties of individual components.