Construction of chimeric immunogens: Bioactive fragment of human IL-1β or polytuftsin (PT) capable of eliciting immune responses to HIV peptides

Abstract

In this study, we have examined the effect of linking of bloactive fragment of human IL-1β (163-171) or polytuftsin (PT, a synthetic polymer of natural immunomodulator "tuftsin") with synthetic peptides of HIV on the induction of immune response to the synthetic peptides. A panel of synthetic peptides representing defined region of gp41, gp120 and gag were used as antigens. Immunomodulators linked peptides (i.e. peptide-IL-1β or peptide-PT) or peptide dimers were employed for immunization in Balb/c mice. Mice immunized with the peptide-immunomodulator develop effective T-cell proliferation,in vitro cytokine release and higher antibody production, but not with peptide dimers. We also found that peptide-immunomodulators induced high level of IgG2a antibody production. Furthermore, there was a positive correlation between the levels of cytokine (IL-2 & IFN-γ) and IgG isotype production. Thus it would appear that incorporation of IL-1β fragment or PT selectively enhances the Th1 type response to these peptides and may therefore be important for virus neutralization and clearance. However, the effect of IL-1β fragment was found to be more pronounced than polytuftsin. Such an approach may provide effective vaccination against other infectious diseases.

Keywords: Human interleukin-1β; Th-cells; chimeric immunogens; cytokines; polytuftsin.