Assessing the tolerability and versatility of the new Spytag003/Spycatcher003 as a novel bio-conjugation system for displaying protein antigens on the surface of bacteriophage VLPs

About This Grant

PROJECT SUMMARY Peptide and protein antigen vaccines are very safe compared to live-attenuated vaccines. They can be used to immunize anyone and are not associated with a lot of side effects compared to live-attenuated vaccines. However, peptides and proteins are less immunogenic compared to live-attenuated vaccines. To overcome these limitations, peptide antigens have been inserted/displayed on the surface of virus-like particles (VLPs) to increase their size as well as the valency or density of the peptide. VLPs are morphologically and structurally similar to viruses from which the coat proteins are derived from, except for the fact that they lack the viral genome. VLPs are highly immunogenic even at small doses of antigens. Most peptide antigens can be displayed on VLPs by genetic insertion or by chemical conjugation (to make them multivalent and highly immunogenic). However, these two approaches cannot be used for every peptide not to mention protein antigens. The size of an antigen as well as the composition of the antigen most of the time interferes with these two conjugation approaches. These limitations make in very impossible to use identified antigens with neutralizing and protective epitopes in vaccine design. To overcome the limitations with genetic and chemical conjugation approaches, we propose to explore a novel bio-conjugation approach on 4 bacteriophage VLPs (MS2, PP7, AP205, Q). This approach will use the new Spytag003/Spycatcher003 bio-conjugation system developed from the prototype Spytag/Spycatcher. In the proposed study, we will assess the potential of using the new Spytag003/Spycatcher003 bio-conjugation system to display diverse protein antigens on the surface of 4 bacteriophage VLPs. We will assess the versatility of the new bio-conjugation system on these VLPs using diverse protein antigens that differ in origin, size, and conformation.