Development of a versatile vaccination platform based on papaya mosaic virus (PapMV) nanoparticles
June 12-17, 2016
Over the past years, virus-like particles (VLPs) have shown great potential as highly immunogenic subunit vaccines. These non-infectious viral structures mimic the native pathogen’s organisation and conformation. VLPs contain highly repetitive and ordered viral epitopes leading to B cell activation through receptor cross-linking. By displaying heterologous epitopes on VLPs, one can mount an immune response against a different pathogen. These chimeric VLPs serve as presentation scaffold and can sometimes act as adjuvant to boost the immune response. However, VLP assembly can be affected by large epitope insertions altering intra or extra protein interactions impacting its conformation. Even if the insertion is successful, the epitopes have to be exposed at the particle surface to induce an immune response. To circumvent this problem, we have developed a new vaccine platform based on PapMV nanoparticules and sortase A (SrtA) transpeptidase. SrtA catalyzes the covalent conjugation of target antigenic epitopes to already assembled PapMV VLPs harbouring the SrtA recognition motif LPETG. Successful SrtA conjugations were achieved with peptides derived from Influenza (M2e) and HIV (T20). SrtA conjugated PapMV nanoparticles induce strong humoral responses in mice against both M2e and T20 peptides. PapMV-M2e vaccinated mice were protected against a lethal dose of Influenza H1N1 (A/WSN/33). Sera from PapMV-T20 vaccinated mice did not reduce in vitro HIV infection even with the high presence of specific antibodies. This new PapMV-SrtA platform eliminates the need for genetic fusion of the coat protein that can be difficult, time consuming and, sometime, unrealizable. The modification of PapMV VLP post-assembly facilitates its use in the rapid development of new vaccines by changing the nature of the target epitopes conjugated. This could be particularly useful when developing a pandemic vaccine or personalised vaccine for cancer therapy.
Ariane Thérien, Damien Carignan, Gervais Rioux, and Denis Leclerc, "Development of a versatile vaccination platform based on papaya mosaic virus (PapMV) nanoparticles" in "Vaccine Technology VI", Laura Palomares, UNAM, Mexico Manon Cox, Protein Sciences Corporation, USA Tarit Mukhopadhyay, University College London, UK Nathalie Garçon, BIOASTER Technology Research Institute, FR Eds, ECI Symposium Series, (2016). http://dc.engconfintl.org/vaccine_vi/80