The science of present day vaccinology is based on the pioneering discoveries of the late 18th and late 19th centuries and the technologic breakthroughs of the past 60 years. The driving force for the development of new vaccines resides in technologic feasibility, public need and economic incentive for translating the basic knowledge into a product. Past efforts by government to define which particular vaccines to develop were mostly irrelevant to the realistic choices which were made. There is a vast array of viral, bacterial, parasitic and fungal disease agents against which preventative vaccines may be developed, and to this may be added cancer and certain amyloidoses such as Alzheimer’s and ‘mad cow’ diseases. The proven past for vaccines has relied on live, killed, protein and polysaccharide antigens plus the single example of recombinant-expressed hepatitis B vaccine. The validity of redirection of vaccinology to exploration of simplified vaccines such as recombinant vectored and DNA preparations and reductionist vaccines based on peptides of contrived epitope composition remains to be proved. Reductionism imposes vastly increased complexity and difficulty on vaccine development and might not be capable of achievement. The challenge in the 21st century will involve new and uncertain pathways toward worthwhile accomplishments.

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