CD8+ T cells induced by adenovirus-vectored vaccine are capable of preventing establishment of latent murine γ-herpesvirus 68 infection
| Autor: | Emeline Ragonnaud, Peter Johannes Holst, Ditte Rahbæk Boilesen, Henriette Laursen, Anders Tolver, Katja Spiess, Anne-Marie C. Andersson |
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| Rok vydání: | 2018 |
| Předmět: |
medicine.medical_treatment
T cell 030231 tropical medicine Heterologous Biology CD8-Positive T-Lymphocytes Adenoviridae 03 medical and health sciences Mice 0302 clinical medicine Immune system Viral entry medicine Cytotoxic T cell Animals 030212 general & internal medicine Herpesviridae General Veterinary General Immunology and Microbiology Public Health Environmental and Occupational Health Herpesviridae Infections Flow Cytometry Virology Vaccination Mice Inbred C57BL Infectious Diseases medicine.anatomical_structure Molecular Medicine Female Adjuvant CD8 |
| Zdroj: | Vaccine. 37(22) |
| ISSN: | 1873-2518 |
| Popis: | CD8+ T cells are known to control infections, but their role in preventing latent infection from establishing has not been thoroughly investigated. We hypothesized that a potent CD8+ T cell response patrolling the mucosal viral entry points could kill the first infected cells and thereby abrogate the infection before latency is established. To investigate this, replication deficient adenovirus serotype 5 vectors encoding murine γ-herpesvirus-68 CD8+ T cell epitopes linked to the T cell adjuvant Invariant chain, were developed. We show that intranasal vaccination of mice reduces the risk of establishment of latent infection from multiple intranasal ID50 challenges with murine γ-herpesvirus-68 by 81% per exposure at 14 days post vaccination. Protection waned over time, but immune responses were extended by heterologous prime-boost vaccination applied simultaneously intramuscularly and intranasally, and animals vaccinated 66 days prior to challenge showed a strong trend of long-term protection. Our data provides evidence that CD8+ T cells are able to protect against establishment of latent infection. Although the protective efficacy is difficult to maintain over time, this proof-of-concept study suggests a role for a CD8+ T cell arm in future vaccine strategies against latent human viral infections caused by pathogens such as HIV and multiple herpes virus. |
| Databáze: | OpenAIRE |
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