PDF(Pubmed)
Abstract：
Frequent vaccine failure leading to recurrent outbreaks of Foot-and-Mouth Disease (FMD) in livestock populations necessitates the development of a customizable vaccine platform comprising potential antigenic determinants of circulating lineages of FMD viruses. Artificially designed, chimaeric protein-based recombinant vaccines are novel approaches to combat the phylogenetically diverse FMD Virus (FMDV) strains. Among seven recognized serotypes, only serotypes O and A are dominantly circulating in Bangladesh and neighbouring countries of Asia, where transboundary transmission, recurrent outbreaks and emergence of novel lineages of FMDV are highly prevalent. The objective of this study was to develop multi-epitope recombinant proteins, procuring immunogenicity against circulating diverse genotypes of FMDV serotypes O and A. Two chimaeric proteins, named B1 (41.0 kDa) and B3 (39.3 kDa), have been designed to incorporate potential B-cell and T-cell epitopes selected from multiple FMDV strains, including previously reported and newly emerged sub-lineages. After expression, characterization and immunization of guinea pigs with a considerable antigen load of B1 and B3 followed by serological assays revealed the significant protective immunogenicity, developed from the higher (100 µg) doses of both antigens, against most of the currently prevalent serotype O and A strains of FMDV. The efficient expression, antigenic stability, and multivalent immunogenic potency of the chimaeric proteins strongly indicate their credibility as novel vaccine candidates for existing serotypes O and A of FMDV in Bangladesh and surrounding territories.
摘要：
导致家畜群体中口蹄疫（FMD）反复爆发的频繁疫苗失败，需要开发可定制的疫苗平台，该平台包含FMD病毒循环谱系的潜在抗原决定簇。人为设计,基于嵌合蛋白的重组疫苗是对抗系统发育多样性口蹄疫病毒(FMDV)毒株的新方法。在七个公认的血清型中，只有血清型O和A在孟加拉国和亚洲邻国主要流行，其中跨界传播，FMDV的反复爆发和新谱系的出现非常普遍。这项研究的目的是开发多表位重组蛋白，获得针对FMDV血清型O和A的循环不同基因型的免疫原性。命名为B1（41.0kDa）和B3（39.3kDa），已被设计为整合从多种FMDV毒株中选择的潜在B细胞和T细胞表位，包括以前报道的和新出现的子谱系。在表达式之后，用相当大的B1和B3抗原负载对豚鼠进行表征和免疫，然后进行血清学测定显示出明显的保护性免疫原性，从两种抗原的较高剂量（100µg）发展而来，针对大多数目前流行的血清型O和AFMDV菌株。高效的表达，抗原稳定性，嵌合蛋白的多价免疫原性效力强烈表明它们作为孟加拉国和周边地区现有FMDV血清型O和A的新型候选疫苗的可信度。
