Rollier Christine S, Hill Adrian V S, Reyes-Sandoval Arturo
Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom.
The Jenner Institute, University of Oxford, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom.
Vaccine. 2016 Aug 31;34(38):4470-4474. doi: 10.1016/j.vaccine.2016.07.050. Epub 2016 Jul 30.
Viral-vectored vaccines are in clinical development for several infectious diseases where T-cell responses can mediate protection, and responses to sub-dominant epitopes is needed. Little is known about the influence of MVA or adenoviral vectors on the hierarchy of the dominant and sub-dominant T-cell epitopes. We investigated this aspect in mice using a malaria immunogen. Our results demonstrate that the T-cell hierarchy is influenced by the timing of analysis, rather than by the vector after a single immunization, with hierarchy changing over time. Repeated homologous immunization reduced the breadth of responses, while heterologous prime-boost induced the strongest response to the dominant epitope, albeit with only modest response to the sub-dominant epitopes.
病毒载体疫苗正在针对几种可通过T细胞反应介导保护作用且需要对次优势表位作出反应的传染病进行临床开发。关于痘苗病毒（MVA）或腺病毒载体对优势和次优势T细胞表位层次结构的影响，目前了解甚少。我们在小鼠中使用疟疾免疫原对这一方面进行了研究。我们的结果表明，T细胞层次结构受分析时间的影响，而非单次免疫后的载体影响，且层次结构会随时间变化。重复同源免疫会降低反应的广度，而异源初免 - 加强免疫则诱导对优势表位产生最强反应，尽管对次优势表位的反应仅适度。
