While significant work is emerging on the use of protein cage nanomaterials, such as virus like particles (VLPs), in biomedical applications, lingering concerns over the immune response to these materials in vivo remains. Biomedical applications exist where induction of specific immune responses is desired in the creation of new immune responsive therapeutic materials for combating major human health problems and disease. VLPs present a rich biomaterial architecture and platform for displaying antigens in a spatially controlled manner, either on the exterior and/or on the interior, which could be exploited to direct specific immune response pathways. The VLP derived from Salmonella typhimurium bacteriophage P22 has been shown to be a versatile platform for the incorporation of proteins on the VLP interior. Heterologous co-expression of a protein or peptide cargo of choice fused to the P22 scaffolding protein (SP) with P22 coat protein, leads to assembly of the P22 VLP with the Cargo Protein-SP fusion protein incorporated on the interior. Utilizing this approach P22 VLPs containing the conserved nucleoprotein (NP) from influenza on the interior, in a biomimetic fashion, were shown to elicit a broadly protective CD8+ T cell response to influenza that provided multi-strain protection against 100 times lethal doses of influenza. These results provide strong evidence for utilizing our biomimetic approach, which is amendable to the quick production of vaccines to rapidly emerging pathogens. Investigations into a modular approach for attaching antigenic proteins to exterior of the P22 VLP, allowing display of antigens on the exterior or P22, is described. The ability to display antigens on the outside has the potential to activate alternate immunologic pathways, such as production of neutralizing antibodies that prevent pathogen infections. Tailoring the display of the antigen has the potential to allow for control over directing the specific immune pathway activated and response generated by the VLP.

Engineering virus-like particles toward directing protective immunologic responses

249th National Meeting (2015)

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