Sheerin Dylan, Dold Christina, Silva-Reyes Laura, Linder Aline, Pollard Andrew J, Rollier Christine S
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, UK.
Infectious Diseases and Immune Defence Division, Institute of Medical Research (WEHI), The Walter & Eliza Hall, Parkville, VIC, 3052, Australia.
Cell Biosci. 2022 Jun 11;12(1):86. doi: 10.1186/s13578-022-00809-3.
Disease caused by the capsular group B meningococcus (MenB) is the leading cause of infectious death in UK infants. A novel adenovirus-based vaccine encoding the MenB factor H binding protein (fHbp) with an N-terminal dual signal sequence induces high titres of protective antibody after a single dose in mice. A panel of N-terminal signal sequence variants were created to assess the contribution of components of this sequence to transgene expression kinetics of the encoded antigen from mammalian cells and the resultant effect on immunogenicity of fHbp.
The full-length signal sequence (FL SS) resulted in superior early antigen expression compared with the panel of variants, as measured by flow cytometry and confocal imaging, and supported higher bactericidal antibody levels against the expressed antigen in mouse sera < 6 weeks post-immunisation than the licensed four component MenB vaccine. The FL SS also significantly increased antigen-specific T cell responses against other adenovirus-encoded bacterial antigens in mice.
These findings demonstrate that the FL SS enhances immunogenicity of the encoded antigen, supporting its inclusion in other viral vectored bacterial antigen transgenes.
B 群脑膜炎奈瑟菌（MenB）引起的疾病是英国婴儿感染性死亡的主要原因。一种新型腺病毒载体疫苗，编码带有 N 端双信号序列的 MenB 因子 H 结合蛋白（fHbp），在小鼠单次接种后可诱导产生高滴度的保护性抗体。构建了一组 N 端信号序列变体，以评估该序列各组分对编码抗原在哺乳动物细胞中表达动力学的贡献，以及对 fHbp 免疫原性的最终影响。
通过流式细胞术和共聚焦成像检测，全长信号序列（FL SS）与变体组相比，早期抗原表达更优，且在免疫后<6 周的小鼠血清中，针对表达抗原的杀菌抗体水平高于已获许可的四组分 MenB 疫苗。FL SS 还显著增强了小鼠针对其他腺病毒编码细菌抗原的抗原特异性 T 细胞反应。
这些发现表明，FL SS 增强了编码抗原的免疫原性，支持将其纳入其他病毒载体细菌抗原转基因中。
