RESUMO
Immune responses diminish with age resulting in an increased susceptibility of the elderly to infectious agents and an inability to mount protective immune responses to vaccines. Immunosenescence affects multiple aspects of the immune system, including CD8(+) T cells, which control viral infections and are assumed to prevent the development of cancers. In this study, we tested if CD8(+) T cell responses in aged mice could be enhanced through a vaccine that concomitantly expresses Ag and a molecule that blocks an immunoinhibitory pathway. Specifically, we tested a vaccine based on a replication-defective chimpanzee-derived adenovirus vector expressing the nucleoprotein (NP) of influenza A virus as a fusion protein with the HSV type 1 glycoprotein D, which through binding to the herpes virus entry mediator, blocks the immunoinhibitory herpes virus entry mediator B and T lymphocyte attenuator/CD160 pathways. Our results show that the vaccine expressing a fusion protein of NP and glycoprotein D induces significantly higher NP-specific CD8(+) T cell responses in young and aged mice compared with the vaccine expressing NP only.
Assuntos
Envelhecimento/imunologia , Linfócitos T CD8-Positivos/imunologia , Epitopos de Linfócito T/imunologia , Vírus da Influenza A/imunologia , Membro 14 de Receptores do Fator de Necrose Tumoral/antagonistas & inibidores , Transdução de Sinais/imunologia , Regulação para Cima/imunologia , Animais , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/virologia , Linhagem Celular , Epitopos de Linfócito T/genética , Feminino , Vetores Genéticos/imunologia , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/imunologia , Humanos , Epitopos Imunodominantes/genética , Epitopos Imunodominantes/imunologia , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Nucleocapsídeo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/imunologia , Receptores Imunológicos/genética , Membro 14 de Receptores do Fator de Necrose Tumoral/fisiologia , Proteínas Recombinantes de Fusão/imunologia , Transdução de Sinais/genética , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/antagonistas & inibidores , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/fisiologia , Proteínas do Core Viral/genética , Proteínas do Core Viral/imunologiaRESUMO
Post Traumatic Stress Disorder (PTSD) is reported to be caused by traumatic events that are outside the range of usual human experiences including (but not limited to) military combat, violent personal assault, being kidnapped or taken hostage and terrorist attacks. Initial data suggests that 1 out of 6 returning Iraq War military personnel are exhibiting symptoms of depression, anxiety and PTSD. Virtual Reality (VR) exposure therapy has been used in previous treatments of PTSD patients with reports of positive outcomes. The aim of the current paper is to specify the rationale, design and development of an Iraq War PTSD VR application that is being created from the virtual assets that were initially developed for theX-Box game entitled Full Spectrum Warrior which was inspired by a combat tactical training simulation, Full Spectrum Command.