The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.
Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, OX3 7LE, UK.
Sci Rep. 2017 Aug 4;7(1):7284. doi: 10.1038/s41598-017-07246-0.
The majority of routinely given vaccines require two or three immunisations for full protective efficacy. Single dose vaccination has long been considered a key solution to improving the global immunisation coverage. Recent infectious disease outbreaks have further highlighted the need for vaccines that can achieve full efficacy after a single administration. Viral vectors are a potent immunisation platform, benefiting from intrinsic immuno-stimulatory features while retaining excellent safety profile through the use of non-replicating viruses. We investigated the scope for enhancing the protective efficacy of a single dose adenovirus-vectored malaria vaccine in a mouse model of malaria by co-administering it with vaccine adjuvants. Out of 11 adjuvants, only two, Abisco-100 and CoVaccineHT, enhanced vaccine efficacy and sterile protection following malaria challenge. The CoVaccineHT adjuvanted vaccine induced significantly higher proportion of antigen specific central memory CD8 cells, and both adjuvants resulted in increased proportion of CD8 T cells expressing the CD107a degranulation marker in the absence of IFNγ, TNFα and IL2 production. Our results show that the efficacy of vaccines designed to induce protective T cell responses can be positively modulated with chemical adjuvants and open the possibility of achieving full protection with a single dose immunisation.
大多数常规使用的疫苗需要进行两到三次免疫接种才能达到完全的保护效力。单次接种疫苗长期以来一直被认为是提高全球免疫覆盖率的关键解决方案。最近的传染病爆发进一步突出了需要能够在单次给药后达到完全疗效的疫苗。病毒载体是一种有效的免疫接种平台，受益于固有免疫刺激特性，同时通过使用非复制病毒保持优异的安全性。我们通过与疫苗佐剂共同给药，研究了在疟疾小鼠模型中增强单次剂量腺病毒载体疟疾疫苗的保护效力的范围。在 11 种佐剂中，只有 Abisco-100 和 CoVaccineHT 两种佐剂增强了疫苗的效力和对疟疾挑战的无菌保护。CoVaccineHT 佐剂疫苗诱导了更高比例的抗原特异性中央记忆 CD8 细胞，并且两种佐剂都导致 CD8 T 细胞表达 CD107a 脱颗粒标记物的比例增加，而不产生 IFNγ、TNFα 和 IL2。我们的研究结果表明，旨在诱导保护性 T 细胞反应的疫苗的效力可以通过化学佐剂进行积极调节，并为单次免疫接种实现完全保护提供了可能性。
