Development and clinical application of new polyvalent combined paediatricvaccines

The availability of combined vaccines containing protective antigens agains t the majority of (ideally ail) diseases for which universal immunization i s recommended in infancy would simplify the implementation, increase the ac ceptance, reduce the global cost of immunization programmes and improve dis ease control? while offering the possibility of disease elimination or even pathogen eradication. The desirability of combined vaccines is further enh anced, and made more urgent, because of the increasing number of diseases t hat can be prevented by vaccination. The complicated logistics of administe ring different vaccines that each require several inoculations is a signifi cant barrier to successful immunization of a population. Furthermore, inter est in immunization is continuously gaining momentum since it is now genera lly recognised that vaccines are among the safest and most cost-effective m edical interventions for infectious diseases that continue, in spite of the widespread use of efficacious antimicrobial drugs, to be an important caus e of morbidity and mortality. This burden is likely to increase due to the development of antimicrobial resistance. Basic research on new vaccines or improvement of existing ones such as the use of new technologies may be car ried out in academic or other non-industrial laboratories but development w ork, including the necessary extensive clinical testing, that lead to produ cts that can be approved for routine use is usually co-ordinated and financ ed by commercial companies. The decision to develop any particular combined vaccine will therefore be influenced not only by its medical desirability and technical feasibility but also the potential financial returns that the required investments in time and resources may bring to the company. FLU m ajor vaccine manufacturers are currently working, either alone or through s trategic alliances, towards developing more polyvalent vaccines by adding a ntigens such as inactivated polio virus, conjugated Haemophilus influenzae type b polysaccharide and hepatitis B surface antigen to the diphtheria-tet anus-pertussis vaccine either in its 'classical' (whole-cell) or more purif ied (acellular) formulations. Experience is showing that the development of combined vaccines involves much more than the simple mixing of existing an tigens. Possible incompatibilities or mutual interferences between the anti gens themselves, or between excipients, preservatives, adjuvants, residual contaminants, stabilisers and suspending fluids make it mandatory that each formulation be thoroughly tested for quality, stability, efficacy and safe ty. Furthermore the ability to produce and control it consistently must be established before it can be licensed for commercial use. The progress bein g made in this field is reviewed. (C) 1999 Elsevier Science Ltd. All rights reserved.