Abstract:
Foot-and-mouth disease (FMD) is an acute zoonosis causes significant economic losses. Vaccines able to stimulate efficient protective immune responses are urgently needed. In this study, Escherichia coli-derived recombinant VP1 of serotype A and O FMD virus (FMDV) was conjugated to thermostable scaffold lumazine synthase (LS) or Quasibacillus thermotolerans encapsulin (QtEnc) using a robust plug-and-display SpyTag/SpyCatcher system to generate multimeric nanovaccines. These nanovaccines induced highly potent antibody responses in vaccinated mice. On day 14 after the first immunisation, antibody titres were approximately 100 times higher than those of monomer antigens. Both vaccines induced high and long-term IgG antibody production. Moreover, the QtEnc-VP1 nanovaccine induced higher antibody titres than the LS-VP1 nanovaccine. The nanovaccines also induced Th1-biased immune responses and higher levels of neutralising antibodies. These data indicated that FMDV nanovaccines generated by conjugating VP1 with a thermostable scaffold are highly immunogenic and ideal candidates for FMDV control in low-resource areas.
摘要:
口蹄疫(FMD)是一种引起重大经济损失的急性人畜共患病。迫切需要能够刺激有效保护性免疫应答的疫苗。在这项研究中,使用强大的插件和展示SpyTag/SpyCatcher系统,将血清型A和OFMD病毒(FMDV)的大肠杆菌衍生的重组VP1与热稳定的支架lumazine合酶(LS)或耐热拟杆菌封装蛋白(QtEnc)缀合,以产生多聚纳米疫苗。这些纳米疫苗在接种的小鼠中诱导高度有效的抗体应答。第一次免疫后第14天,抗体滴度比单体抗原高约100倍。两种疫苗均诱导高和长期IgG抗体产生。此外,QtEnc-VP1纳米疫苗诱导的抗体滴度高于LS-VP1纳米疫苗。纳米疫苗还诱导Th1偏向的免疫应答和更高水平的中和抗体。这些数据表明,通过将VP1与热稳定的支架缀合而产生的FMDV纳米疫苗是低资源地区FMDV控制的高度免疫原性和理想候选物。