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Open Access Highly Accessed Research

Engineering of papaya mosaic virus (PapMV) nanoparticles with a CTL epitope derived from influenza NP

Cindy Babin, Nathalie Majeau and Denis Leclerc*

Author Affiliations

Department of Microbiology, Infectiology and Immunology, Infectious Disease Research Center, Laval University, 2705 boul. Laurier, Quebec city, PQ G1V 4G2, Canada

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Journal of Nanobiotechnology 2013, 11:10  doi:10.1186/1477-3155-11-10

Published: 4 April 2013

Abstract

Background

The ever-present threat of infectious disease, e.g. influenza pandemics, and the increasing need for new and effective treatments in immunotherapy are the driving forces that motivate research into new and innovative vaccine platforms. Ideally, such platforms should trigger an efficient CTL response, be safe, and easy to manufacture. We recently developed a novel nanoparticle adjuvant comprised of papaya mosaic virus (PapMV) coat protein (CP) assembled around an RNA. The PapMV nanoparticle is an efficient vaccine platform in which the peptide antigen is fused to the C-terminus of the PapMV CP, leading to nanoparticles presenting surface-exposed epitope. The fusion stabilizes the epitope and improves its immunogenicity. We found recently that C-terminal fusions are not always efficient, depending on the nature of the peptide fused to the platform.

Results

We chose a CTL epitope derived from the nucleocapsid (NP) of influenza virus (NP147-155) for this proof-of-concept demonstration. Recombinant nanoparticles harbouring a fusion at the N-terminus were more efficient in triggering a CTL response. Efficacy appeared to be linked to the stability of the nanoparticles at 37°C. We also showed that discs—smaller than nanoparticles—made of 20 subunits of PapMV CP are less efficient for induction of a CTL response in mice, revealing that assembly of the recombinant PapMV CP into nanoparticles is crucial to triggering an efficient CTL response.

Conclusion

The point of fusion on the PapMV vaccine platform is critical to triggering an efficient CTL response. Efficacy is linked to nanoparticle stability; nanoparticles must be stable at 37°C but remain susceptible to cellular proteases to ensure efficient processing of the CTL epitope by cells of the immune system. The results of this study improve our understanding of the PapMV vaccine platform, which will facilitate the design of efficient vaccines to various infectious threats.

Keywords:
Papaya mosaic virus (PapMV); Vaccine platform; Rod shape nanoparticles; Influenza