College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China.
Virol Sin. 2011 Jun;26(3):190-7. doi: 10.1007/s12250-011-3174-0. Epub 2011 Jun 12.
To develop a safe and efficient recombinant subunit vaccine to foot-and-mouth disease virus (FMDV) type Asia 1 in sheep, a tandem repeated multiple-epitope gene consisting of residues 137-160 and 197-211 of the VP1 gene of FMDV was designed and artificially synthesized. The biologically functional molecule, the ovine IgG heavy constant region (oIgG) as a protein carrier was introduced for design of the multiple-epitope recombinant vaccine and recombinant expression plasmids pET-30a-RE and pET-30a-RE-oIgG were successfully constructed. The recombinant proteins, RE and RE-oIgG, were expressed as a formation of inclusion bodies in E. coli. The immune potential of this vaccine regime in guinea pigs and sheep was evaluated. The results showed that IgG could significantly enhance the immune potential of antigenic epitopes. The recombinant protein RE-oIgG could not only elicit the high levels of neutralizing antibodies and lymphocytes proliferation responses in the vaccinated guinea pigs, but confer complete protection in guinea pigs against virus challenge. Although the recombinant protein RE could not confer protection in the vaccinated animals, it could delay the appearance of the clinical signs and reduce the severity of disease. Inspiringly, the titers of anti-FMDV neutralizing antibodies elicited in sheep vaccinated with RE-oIgG was significantly higher than that for the RE vaccination. Therefore, we speculated that this vaccine formulation may be a promising strategy for designing a novel vaccine against FMDV in the future.
为了开发一种安全有效的绵羊口蹄疫病毒（FMDV）亚洲 1 型重组亚单位疫苗，设计并人工合成了串联重复的多表位基因，该基因由 FMDV VP1 基因的 137-160 位和 197-211 位残基组成。为了设计多表位重组疫苗，引入了具有生物功能的分子——绵羊 IgG 重恒定区（oIgG）作为蛋白质载体，并成功构建了重组表达质粒 pET-30a-RE 和 pET-30a-RE-oIgG。重组蛋白 RE 和 RE-oIgG 在大肠杆菌中以包涵体的形式表达。在豚鼠和绵羊中评估了这种疫苗方案的免疫潜力。结果表明，IgG 可以显著增强抗原表位的免疫潜力。重组蛋白 RE-oIgG 不仅能在接种豚鼠中引起高水平的中和抗体和淋巴细胞增殖反应，还能完全保护豚鼠免受病毒攻击。虽然重组蛋白 RE 不能在接种动物中提供保护，但它可以延迟临床症状的出现并减轻疾病的严重程度。令人鼓舞的是，用 RE-oIgG 接种的绵羊产生的抗 FMDV 中和抗体滴度明显高于 RE 接种的绵羊。因此，我们推测这种疫苗配方可能是未来设计 FMDV 新型疫苗的有前途的策略。
