Natural viral proteins cannot constantly be used as optimal vaccines because they do not always stimulate efficiently the immune system. In December 1 Journal of Clinical Investigation, Jeffrey Ahlers and colleagues from National Institutes of Health, Bethesda, USA, show that sequence modification of natural viral proteins to increase epitope affinity for class II MHC molecules (epitope enhancement) can improve immunogenicity.

Ahlers et al. found that modification of a Th cell epitope to increase binding to MHC causes quantitatively more T cells to undergo upregulation of CD40 ligant. This induced more polarizing antigen presenting cells that act back on the T helper cell to produce a Th1-polarized response, as well as higher levels of cytotoxic T lymphocytes and protection against viral infection (J Clin Invest 2001, 108:1677-1685).

"If such enhanced epitopes can be shown to activate costimulatory pathways and to increase Th1 polarization in other settings,...