Engineering of Papaya Mosaic Virus (PapMV) Nanoparticles through Fusion of the HA11 Peptide to Several Putative Surface-Exposed Sites

Rioux, Gervais; Babin, Cindy; Majeau, Nathalie; Leclerc, Denis

doi:10.1371/journal.pone.0031925

Cited by 37 publications

(37 citation statements)

References 19 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, we have shown that various foreign Ags can be fused to the surface of the PapMV without affecting its ability to self-assemble. Vaccination with such nanoparticles generates a specific cellular and humoral immune response against displayed Ags and provides protection against various viral infection models (19,(22)(23)(24)(25). Moreover, we have demonstrated that the fused Ags are efficiently cross-presented on MHC class I of human APCs and cause the expansion of human Ag-specific T cells (26).…”

mentioning

confidence: 93%

Nanoparticle Adjuvant Sensing by TLR7 Enhances CD8+ T Cell–Mediated Protection from Listeria Monocytogenes Infection

Lebel

Daudelin

Chartrand

et al. 2014

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Developing new adjuvants and vaccination strategies is of paramount importance to successfully fight against many life-threatening infectious diseases and cancer. Very few adjuvants are currently authorized for human use, and these mainly stimulate a humoral response. However, specific Abs are not sufficient to confer protection against persisting infections or cancer. Therefore, development of adjuvants and immunomodulators able to enhance cell-mediated immune responses represents a major medical need. We recently showed that papaya mosaic virus nanoparticles (PapMV), self-assembled from the coat protein of a plant virus and a noncoding ssRNA molecule, are highly immunogenic in mice. PapMV can be used either as a vaccine delivery platform, through fusion of various epitopes to the coat protein or as adjuvant to enhance humoral immune responses against coadministered Ags or vaccines. However, the mechanisms that confer these immunomodulatory properties to PapMV and its ability to enhance T cell vaccines remain unknown. Using immunization studies in mice, we demonstrate in this paper that PapMV represents a novel TLR7 agonist with strong immunostimulatory properties. More importantly, pretreatment with PapMV significantly improves effector and memory CD8+ T cell responses generated through dendritic cell vaccination increasing protection against a Listeria monocytogenes challenge.

show abstract

mentioning

confidence: 93%

Nanoparticle Adjuvant Sensing by TLR7 Enhances CD8+ T Cell–Mediated Protection from Listeria Monocytogenes Infection

Lebel

Daudelin

Chartrand

et al. 2014

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Fusion of a peptide to the PapMV vaccine platform could affect its stability, and potentially the ability to mount an immune response to the fused epitope [8]. As temperature can affect protein stability, we thus measured the influence of temperature on the aggregation of recombinant nanoparticles using DLS.…”

Section: Resultsmentioning

confidence: 99%

“…We showed previously that non-infectious nanoparticles made of recombinant PapMV CP are similar in shape and appearance to wild-type virus purified from plants [3]. PapMV nanoparticles were used previously as a vaccine platform technology to improve the immunogenicity of a peptide antigen fused to the nanoparticle structure [4-8]. The PapMV vaccine platform can induce a long-lasting memory response to an antigen fused on its surface [4].…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies showed the capacity of PapMV nanoparticles to trigger a CTL response, in both in vitro and in vivo models, when the CTL epitope was fused to the C-terminus of the CP [6,7,9]. Although PapMV tolerates insertion of several peptides to its C-terminus [4-7,10], a recent study revealed that N-terminal fusion of some peptides is also tolerated [8]. Depending on the nature of the amino acid sequence, some peptides can interfere with the CP assembly or with nanoparticle stability, which can affect their ability to stimulate an humoral response.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

2013

Self Cite

View full text Add to dashboard Cite

BackgroundThe 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.ResultsWe 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.ConclusionThe 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.

show abstract

“…[28]. Two new tested insertion sites in CP led to the production of recombinant proteins capable of assembly into PapMV nanoparticles [29].…”

Section: Discussionmentioning

confidence: 99%

New positions for peptide presentation in Potato virus X capsid protein

et al. 2015

View full text Add to dashboard Cite

viruses represents potentially a promising new delivery and adjuvant system mainly for the following reasons: (i) the capsid of plant virus represents a scaffold exposing desired epitopes to the immune system in an abundant and organized manner and can serve as an adjuvant by itself, (ii) plant viruses are not infectious to animals, lowering the safety risk associated with their deployment, and (iii) scalability [3,4].Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections worldwide. Infection by high risk HPVs is causally associated with cervical cancer, which represents the second most common cancer among women (after breast cancer) [5]. The most common oncogenic HPV genotypes are 16 and 18, together causing approximately 70 % of all cervical cancers, while HPV 16 alone causing 50 % of all cervical cancers [6]. The E7 oncoprotein plays an important role in both malignant transformation and in the maintenance of the transformed state of HPV infected cells. This represents a promising target for immunotherapy because the E7 oncoprotein is expressed in all cervical tumors and in precancerous lesions [7]. The main known role of E7 oncoprotein in virus cycle is to prevent cell death by binding tumor-suppressor protein Rb (pRb), resulting in the dissociation of pRB from E2F-family transcription factors and the premature cell progression into the S phase of the cell cycle which leads to uncontrollable cell division [8].Potato virus X (PVX) belongs to the order Tymovirales, family Alphaflexiviridae and genus Potexvirus. It is a filamentous, positive single stranded RNA (+ssRNA) virus. Virus particles are about 515 nm long and have about 13 nm in diameter. The PVX genome is capped, has a poly(A) tail and encodes five open reading frames (viral replicase, three movement proteins belonging to the triple-gene block family and capsid protein -approximately 1 300 CP subunits per virion) [9]. The PVX CP can be used for presentation by direct or indirect fusion of a desired protein or peptide to the N-terminus [10][11][12]. Recently, it has been also shown that the C-terminus of PVX CP can be used for protein presentation [13]. However, the Abstract: Potato virus X (PVX) is widely used as a peptide presentation system in plant biotechnology, mostly for transient expression of desired peptides fused to the N-terminus of its capsid protein (CP). Here we describe testing/investigation of new positions for peptide presentation based on seven putative surface loops of PVX CP. We performed bacterial expression of fourteen different PVX CPs modified by the insertion of the epitope derived from the E7 oncoprotein (E7 epitope) of Human papillomavirus type 16 fused with His tag. The expression from vector pMPM-A4Ω in Escherichia coli MC1061 was performed to evaluate the capacity of the PVX CP platform to tolerate the insertion of E7 epitope fused with His tag in the seven putative surface loops. The immunological characteristics of expressed epitopes were assessed by Western blot using both anti-P...

show abstract

Engineering of Papaya Mosaic Virus (PapMV) Nanoparticles through Fusion of the HA11 Peptide to Several Putative Surface-Exposed Sites

Cited by 37 publications

References 19 publications

Nanoparticle Adjuvant Sensing by TLR7 Enhances CD8+ T Cell–Mediated Protection from Listeria Monocytogenes Infection

Nanoparticle Adjuvant Sensing by TLR7 Enhances CD8+ T Cell–Mediated Protection from Listeria Monocytogenes Infection

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

New positions for peptide presentation in Potato virus X capsid protein

Contact Info

Product

Resources

About