Centre for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, Denmark; InProTher ApS, DK2200 Copenhagen, Denmark.
Centre for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, Denmark; NIA, NIH, Baltimore MD, USA.
Vaccine. 2019 May 16;37(22):2952-2959. doi: 10.1016/j.vaccine.2019.04.034. Epub 2019 Apr 18.
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 linkedto 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.
CD8+ T 细胞被认为可以控制感染，但它们在防止潜伏感染方面的作用尚未得到彻底研究。我们假设，在潜伏感染建立之前，一种强大的 CD8+ T 细胞反应可以在黏膜病毒进入点巡逻，杀死第一个受感染的细胞，从而阻断感染。为了研究这一点，我们开发了复制缺陷型腺病毒血清型 5 载体，编码与 T 细胞佐剂不变链相连的小鼠γ疱疹病毒-68 CD8+ T 细胞表位。我们发现，鼻腔接种疫苗可使小鼠在 14 天接种后，每暴露一次，就能将潜伏感染建立的风险降低 81%，其效价为 50%。保护作用随时间减弱，但通过同时肌肉内和鼻腔内接种异源初免-加强疫苗，可延长免疫反应，而在挑战前 66 天接种疫苗的动物则显示出长期保护的强烈趋势。我们的数据提供了证据表明，CD8+ T 细胞能够防止潜伏感染的建立。尽管保护效果很难随时间维持，但这项概念验证研究表明，针对 HIV 和多种疱疹病毒等病原体引起的潜伏性人类病毒感染，CD8+ T 细胞可能在未来的疫苗策略中发挥作用。
