In silico Guided Design of a Synthetic Peptide Vaccine Construct from Intrinsically Disordered Regions of the Group Specific Antigen Polyprotein
Gwyneth Anne A. Rabanal, Arturo Lano GaitanoBackground:
The group specific antigen (Gag) polyprotein of human immunodeficiency virus-1 is an essential protein for the formation of virus particles and has emerged as a target for potential therapeutic interventions. Identification of viable linear B-Cell and cytotoxic T-Cell epitopes within intrinsically disordered regions within the Gag polyprotein can be achieved through immunoinformatics and related computational tools. The identified epitopes can be incorporated into a synthetic peptide vaccine construct designed
Methods:
Linear B-Cell and cytotoxic T-Cell epitopes were identified through B-Cell and cytotoxic T-Cell epitope prediction tools found in the Immune Epitope Database. These were assessed for antigenicity, allergenicity, toxicity, cross-reactivity, and sequence conservation
Results:
A total of 9 B-Cell and 2 T-Cell epitopes were identified as viable candidates, with both T-Cell epitopes and 7 B-Cell epitopes found in disordered regions. Different portions of a vaccine construct containing these epitopes, RS09, pan HLA DR-binding epitope, and the appropriate linkers binds spontaneously with Toll-like receptor 4 and induced increases and maintenance in memory B-Cell and memory helper T-Cell populations, with corresponding increases of cytotoxic T-Cell populations as well as antibody and cytokine concentrations.
Conclusions:
A synthetic peptide vaccine construct from B-Cell and T-Cell epitopes found in disordered regions that induces immune responses in simulations was designed