Pitfalls of reductionism in the design of peptide-based vaccines

It is widely believed that all biological phenomena can be reduced to chemistry and physics. Such a reductionist view disregards the fact that complex biological systems have relational (also called emergent) properties that their constituents lack and that cannot be deduced or predicted from the properties of the isolated components. When the individual components of the immune system are studied in isolation, many interconnections are lost and it is not possible to understand how the system functions at the level of the organism as a whole. Our increasing knowledge of the antigenic structure of viral proteins has also been of little help for improving the immunogenicity of individual viral epitopes and for enhancing their capacity to elicit a protective immune response against viral infection. When molecular design principles are used to optimize the binding properties of a synthetic peptide epitope with respect to one neutralizing monoclonal antibody, this does not ensure that the peptide, when used as immunogen, will be able to induce neutralizing antibodies that protect against disease. A reductionist approach does not provide the information required for designing peptide immunogens that will elicit neutralizing rather than non-neutralizing antibody responses.