RESUMO
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.
Assuntos
Adjuvantes Imunológicos , Linfócitos T CD8-Positivos/imunologia , Listeria monocytogenes/imunologia , Listeriose/prevenção & controle , Glicoproteínas de Membrana/agonistas , Subpopulações de Linfócitos T/imunologia , Receptor 7 Toll-Like/agonistas , Tymovirus/imunologia , Vacinação , Imunidade Adaptativa , Animais , Células Dendríticas/imunologia , Avaliação Pré-Clínica de Medicamentos , Feminino , Imunoglobulina G/biossíntese , Memória Imunológica , Interferon Tipo I/imunologia , Listeriose/imunologia , Glicoproteínas de Membrana/deficiência , Glicoproteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Fator 88 de Diferenciação Mieloide/deficiência , Fator 88 de Diferenciação Mieloide/imunologia , Nanopartículas , Ovalbumina/imunologia , RNA Viral/imunologia , Receptor de Interferon alfa e beta/deficiência , Receptor 7 Toll-Like/deficiência , Receptor 7 Toll-Like/imunologia , Tymovirus/genéticaRESUMO
This randomized clinical trial compared cognitive-behavioral therapy (CBT), applied relaxation (AR), and wait-list control (WL) in a sample of 65 adults with a primary diagnosis of generalized anxiety disorder (GAD). The CBT condition was based on the intolerance of uncertainty model of GAD, whereas the AR condition was based on general theories of anxiety. Both manualized treatments were administered over 12 weekly 1-hour sessions. Standardized clinician ratings and self-report questionnaires were used to assess GAD and related symptoms at pretest, posttest, and at 6-, 12-, and 24-month follow-ups. At posttest, CBT was clearly superior to WL, AR was marginally superior to WL, and CBT was marginally superior to AR. Over follow-up, CBT and AR were equivalent, but only CBT led to continued improvement. Thus, direct comparisons of CBT and AR indicated that the treatments were comparable; however, comparisons of each treatment with another point of reference (either waiting list or no change over follow-up) provided greater support for the efficacy of CBT than AR.