Novel Plant Virus-Based Vaccine Induces Protective Cytotoxic T-Lymphocyte-Mediated Antiviral Immunity through Dendritic Cell Maturation

Lacasse, Patrick; Denis, Jérôme Alexandre; Lapointe, Réjean; Leclerc, Denis; Lamarre, Alain

doi:10.1128/jvi.01811-07

Cited by 74 publications

(78 citation statements)

References 52 publications

(53 reference statements)

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“…Moreover, similar results were obtained following depletion of BST2-positive cells, which in naive mice, mainly consists of pDCs, the main source of IFN-a. We thus suggest that following immunization with PapMV, pDCs, and most certainly other APCs, as we have shown previously (22,30,35), take up the particles and degrade them in the endosome allowing recognition of the ssRNA by TLR7, which leads to a massive production of IFN-a in a MYD88 and IRF5/7-dependent fashion. Subsequently, IFN-a is detected by various immune cells through IFNAR leading to their activation as observed by an increased expression of activation markers such as CD69, costimulatory molecules like CD86 and MHC proteins, and the production of other immune mediators such as the proinflammatory cytokine IL-6.…”

Section: Discussionmentioning

confidence: 99%

“…In previous studies, we showed that following i.v. immunization, splenic DCs take up PapMV in vivo and acquire a mature phenotype (22). In addition, we recently showed that s.c (34).…”

Section: Discussionmentioning

confidence: 99%

“…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: 90%

“…At present, there are two vaccines used in humans derived from VLPs: The hepatitis B virus vaccine and the human papillomavirus vaccine. We have previously shown that papaya mosaic virus-like nanoparticles (PapMV) are efficiently recognized and taken up by immune cells leading to their activation (22). 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.…”

mentioning

confidence: 97%

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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%

“…In previous studies, we showed that following i.v. immunization, splenic DCs take up PapMV in vivo and acquire a mature phenotype (22). In addition, we recently showed that s.c (34).…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 90%

mentioning

confidence: 97%

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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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“…Por exemplo o sistema de expressão da CP do vírus filamentoso flexuoso Papaya mosaic virus, foi utilizado para a engenharia de nanopartículas quiméricas recombinantes, e podem ser utilizados como adjuvante (DENIS et al, 2008, SAVARD et al, 2011) ou como plataforma de vacinas (DENIS et al, 2007, LACASSE et al, 2008. As nanopartículas parecem ser percebidas pelo sistema imune inato, sendo assim, excelentes moléculas imuno-modulatórias para melhorar a vacina da gripe sazonal (SAVARD et al, 2011) ou condidato à vacina da febre tifóide (ACOSTA-RAMIREZ et al, 2008).…”

Section: Predição Da Estrutura Tridimensional Da Gvacpunclassified