Optimizing antiviral peptide vaccines

Costimulatory receptors on T cell surface modulate the signaling pathways that activate lymphocytes against specific antigens, often with profound effects on the ultimate host response. Ahlers et al. have followed the immune cell interactions that lead to the development of antiviral immunity in animals vaccinated with an HIV peptide. These interactions, occurring between antigen-presenting dendritic cells (DCs) and antigen-specific Th cells and CTLs, are altered fundamentally depending on whether the co-stimulatory protein CD40L is induced on Th cells. The authors compare the effects of two, nearly identical peptide vaccines. One carries an HIV surface epitope linked to a helper peptide that binds a known Class II MHC molecule, while the other contains a single amino acid substitution in the helper peptide. This subtle change, which retains the antigenic sequence but increases the peptide?s affinity for the MHC molecule, was previously shown to yield a more vigorous CTL response against the HIV sequence. Ahlers et al. now show that the tighter binding activates CD40L expression and results in a qualitatively different response to the vaccine?one in which Th cells are induced to express Th1-type cytokines, thus supporting CTL activity. The native peptide sequence, in contrast, yields a mix of Th1- and Th2-type cytokines and a weak CTL response. If such enhanced epitopes can be shown to activate costimulatory pathways and to increase Th1 polarization in other settings, this work could provide an important strategy for improving peptide vaccines.

---

---