Quantifying the possible cross-reactivity risk of an HPV16 vaccine.

BACKGROUND The potential adverse events associated with vaccination for infectious diseases underscore the need for effective analysis and definition of possible vaccine side effects. Using the HPV16 proteome as a model, we quantified the actual and theoretical risks of anti-HPV16 vaccination, and defined the potential disease spectrum derived from concomitant cross-reactions with the human organism. METHODS We searched the primary sequence of the HPV16 proteome for heptamer aminoacid sequences shared with human proteins using the Protein International Resource database. RESULTS The human proteome contains 82 heptapeptides and two octapeptides found in HPV16. The viral matches are spread among proteins involved in fundamental processes, such as cell differentiation and growth and neurosensory regulation. The human proteins containing the HPV16-derived heptamers include cell-adhesion molecules, leukocyte differentiation antigens, enzymes, proteins associated with spermatogenesis, transcription factors, and neuronal antigens. The number of viral matches and their locations make the occurrence of side autoimmune cross-reactions in the human host following HPV16-based vaccination almost unavoidable. CONCLUSIONS Any antigen-based vaccine needs to be carefully and thoroughly designed and critically screened for potential side effects by comparing sequence similarity at the molecular level.