Qualitative and quantitative effects of 4-1BBL in boosting pre-existing influenza immunity (VAC2P.923)
| Autor: | Angela Zhou, Lisa Wagar, Michael Wortzman, Tania Watts |
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| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 192:72.1-72.1 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.192.supp.72.1 |
| Popis: | Influenza virus induces an acute respiratory infection responsible for up to 500,000 annual deaths, primarily in older persons. CD8+ T cells against conserved influenza proteins confer heterotypic protection, potentially providing a “universal vaccine.” However, live infection only transiently boosts influenza-specific T cell memory, and immunity further declines with age. To improve the longevity of T cell memory, we investigated the effects of stimulating the TNFR-family member 4-1BB. To mimic vaccination of previously flu-immune adults, mice were infected with influenza A/HK-X31 and boosted intranasally one-month later with control replication-deficient adenovirus or adenovirus encoding influenza nucleoprotein (NP) alone (Ad-NP) or NP with 4-1BBL (Ad-NP-4-1BBL). 4-1BBL dramatically enhanced NP-specific CD8+ T cell responses at a dose where Ad-NP had minimal effects. 4-1BBL induced a remarkably long-lived effector-memory population that protects mice against lethal challenge into old age (>1 year old). Increasing the Ad-NP dose did not replicate these effects, and instead caused partial functional exhaustion. Preliminary analysis indicates that the 4-1BBL-induced effector memory T cells have increased expression of IL-7R as well as the transcriptional factor TCF-1 and an increased ratio of T-bet to Eomesodermin. Thus, 4-1BBL in a vaccine vector administered in flu-immune mice induces a potentially unique protective subset of memory CD8+ T cells. |
| Databáze: | OpenAIRE |
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