Augmentation of primary influenza A virus-specific CD8+ T cell responses in aged mice through blockade of an immunoinhibitory pathway.
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.
DiMenna
Lauren
L
Wistar Institute, Philadelphia, PA 19104, USA.
Latimer
Brian
B
Parzych
Elizabeth
E
Haut
Larissa H
LH
Töpfer
Katrin
K
Abdulla
Sarah
S
Yu
Hong
H
Manson
Brian
B
Giles-Davis
Wynetta
W
Zhou
Dongming
D
Lasaro
Marcio O
MO
Ertl
Hildegund C J
HC
D000375:Aging / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D011971:Receptors, Immunologic / Q000235:genetics; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000037:antagonists & inhibitors* / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000037:antagonists & inhibitors / Q000502:physiology; D015854:Up-Regulation / Q000276:immunology*; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology
C488868:BTLA protein, mouse; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins; D011971:Receptors, Immunologic; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011993:Recombinant Fusion Proteins; C506029:Tnfrsf14 protein, mouse; C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014758:Viral Core Proteins