Synthetic Peptide Immunogens as Vaccines

Synthetic peptide immunogens have been shown to elicit antibodies that can react with full-length proteins containing that peptide. Such antibodies are directed against a specific region of the protein chosen in advance by the investigator and so have a predetermined specificity. In basic research, these antibodies are useful in identifying the protein product of an open reading frame, localizing the gene product to particular cells or subcellular organelles, identifying the enzymatic function of a protein product, following the fate of particular regions of a product through protein maturation processes, analyzing the expression of exons following DNA rearrangements and RNA splicing, and purifying the protein by immunoaffinity chromatography techniques. In medicine, such antibodies may provide reagents for passive vaccination, antitoxin therapy, and targeted immunotherapy of neoplasia. The peptides themselves may be used as synthetic vaccines. The immediate future of the synthetic peptide immunogen in medicine is clear--the promise demonstrated in the laboratory must be reduced to safe application in the hospital. Two barriers to this are the selection of precisely the best peptide and the selection of the proper adjuvant. Currently, a brute force approach is utilized to find the best peptide for eliciting the desired antibodies. This is clearly a problem when the pathogenic organism is assayable only in man. Possibly, by combining studies on the antigenicity of the pathogenic organism with an analysis of naturally occurring variants that alter its immunogenicity, peptide selection will be made easier. Also, since the adjuvants and carriers used in the laboratory are in general too harsh for widespread use in humans and animals, much work needs to be done to find suitable adjuvants and carriers. Nonetheless, now that the major conceptual hurdle to synthetic peptide vaccines has been cleared (that is, it is not necessary to reproduce conformation exactly), it should be relatively straightforward to solve the remaining problems.