CD8+ T cells induced by adenovirus-vectored vaccine are capable of preventing establishment of latent murine γ-herpesvirus 68 infection. Issue 22 (16th May 2019)

• Record Type: Journal Article
• Authors: Boilesen, Ditte R.; Ragonnaud, Emeline; Laursen, Henriette; Andersson, Anne-Marie C.; Tolver, Anders; Spiess, Katja; Holst, Peter J.
• Is Part Of: Vaccine. Volume 37:Issue 22(2019)
• Page Start: 2952
• Page End: 2959
• Publication Date: 2019-05-16
• Subjects: Adenoviral vectored vaccine -- CD8 T cells -- Murine gammaherpesvirus 68 -- Invariant chain; BAL Bronchoalveolar Lavage -- ChAd63 chimpanzee adenovirus serotype 63 -- ChAd63-Iipoly Iipoly encoded in ChAd63 -- dpv days post vaccination -- hAd5 human adenovirus serotype 5 -- hAd5-Iipoly Iipoly encoded in hAd5 -- HIV Human Immunodeficiency Virus -- Ii MHC class II associated Invariant chain -- i.n. intranasal -- MHV-68 murine γ-herpesvirus-68 -- qPCR Quantitative Polymerase Chain Reaction -- SIV Simian Immunodeficiency Virus -- YFP Yellow Fluorescent Protein; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2019.04.034
• Languages: English
• ISSNs: 0264-410X

Abstract

Abstract: 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.