Immunotherapy of Allergic Rhinitis: New Therapeutic Opportunities with Virus-like Particles Filled with Cpg Motifs

Klimek, Ludger; Schendzielorz, Philipp; Mueller, Philipp; Saudan, Philippe; Willers, Jörg

doi:10.2500/ajra.2013.27.3875

Cited by 19 publications

(21 citation statements)

References 87 publications

(138 reference statements)

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“…Other VLPs displaying various TLR ligands have provided encouraging results in various pathological settings. In particular, VLPs loaded with CpG oligodeoxynucleotides (TLR9 ligands) have shown a very promising therapeutic potential against cancer (57,58) but also in other context such as allergen-specific immunotherapy (59)(60)(61). Cancer immunotherapy with DC-based vaccines also has provided great promises in the past few years but requires optimization to become fully effective (62,63).…”

Section: Discussionmentioning

confidence: 99%

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

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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.

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Section: Discussionmentioning

confidence: 99%

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

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“…A current dogma of immunotherapy is that the relevant allergens must be incorporated in a successful SIT. However, recent study data could overcome this dogma [22,23].…”

Section: Abstract: Allergen • Asthma • Cpg • Immunotherapy • Rhinitismentioning

confidence: 90%

“…A current dogma of immunotherapy is that the relevant allergens must be incorporated in a successful SIT. However, recent study data could overcome this dogma [22,23].Virus-like particles (VLPs) are self-assembled nanoparticles that do not contain viral RNA or DNA and are therefore not able to replicate. VLPs are usually derived from capsid protein(s) of viruses or bacteriophages and provide a new and interesting vaccine platform for immunotherapy in inhalation allergies [24,25].…”

mentioning

confidence: 97%

Immunotherapy of type-1 allergies with virus-like particles and CpG-motifs

Klimek

Bachmann

Senti

et al. 2014

Expert Review of Clinical Immunology

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Immunotherapy of type-I-allergies is regarded as the most efficient treatment option besides allergen avoidance. Different forms of allergen preparations are used as well as different routes of application. Virus-like particles represent a potent vaccine platform with proven immunogenicity and clinical efficacy. The addition of toll-like receptor ligands and/or depot-forming adjuvants further enhances immune cell activation. This article will focus on the function of virus-like particles loaded with DNA rich in CpG-motifs and discuss clinical experience in treatment of allergic rhinitis. Evidence will be presented that clinically effective treatment can be obtained even in the absence of allergens. Results encourage further investigation of virus-like particles and CpG-motifs in immunotherapy, either as a stand alone product, or as adjuvants for allergen-specific immunotherapy.

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“…We included the well-known Qβ VLP-based allergy vaccine CYT003-QbG10 that contains an encapsulated CpG sequence, so-called QbG10, in table 2, although it does not carry any attached epitope [217,218,219,220,221]. However, this potentially successful vaccine initially originated from epitope-coupling methodology.…”

Section: Vaccines and Vaccine Candidatesmentioning

confidence: 99%

“…It has been demonstrated that MS2 VLPs can be conjugated to peptides recognizing human hepatocellular carcinoma cells and can be loaded with vastly different types of cargo, including low molecular weight chemotherapeutic drugs, siRNA cocktails, protein toxins and nanoparticles, resulting in the selective killing of target cells [268]. The packaging of Qβ VLPs with immunostimulatory CpG sequences led not only to the development of potential allergy vaccines (see above) but also strongly contributed to the general understanding of the mechanics of oligodeoxynucleotide-induced stimulation [217,218,219,220,221,222,223,224,225,226,227,228,229,269,270]. …”

Section: Nonvaccine Applicationsmentioning

confidence: 99%

The True Story and Advantages of RNA Phage Capsids as Nanotools

et al. 2016

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RNA phages are often used as prototypes for modern recombinant virus-like particle (VLP) technologies. Icosahedral RNA phage VLPs can be formed from coat proteins (CPs) and are efficiently produced in bacteria and yeast. Both genetic fusion and chemical coupling have been successfully used for the production of numerous chimeras based on RNA phage VLPs. In this review, we describe advances in RNA phage VLP technology along with the history of the Leviviridae family, including its taxonomical organization, genomic structure, and important role in the development of molecular biology. Comparative 3D structures of different RNA phage VLPs are used to explain the level of VLP tolerance to foreign elements displayed on VLP surfaces. We also summarize data that demonstrate the ability of CPs to tolerate different organic (peptides, oligonucleotides, and carbohydrates) and inorganic (metal ions) compounds either chemically coupled or noncovalently added to the outer and/or inner surfaces of VLPs. Finally, we present lists of nanotechnological RNA phage VLP applications, such as experimental vaccines constructed by genetic fusion and chemical coupling methodologies, nanocontainers for targeted drug delivery, and bioimaging tools.

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Immunotherapy of Allergic Rhinitis: New Therapeutic Opportunities with Virus-like Particles Filled with Cpg Motifs

Abstract: Results encourage further investigations of VLPs and CpG motifs as adjuncts to or even alternative candidates for immunotherapy of allergic disorders.

Cited by 19 publications

References 87 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

Immunotherapy of type-1 allergies with virus-like particles and CpG-motifs

The True Story and Advantages of RNA Phage Capsids as Nanotools

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