Xu Shi, Li Jing, Xu Mengwei, Cai Yafei, Qian Yingjuan, Liu Rui, He Qing, Fei Caiyi, Wang Aili, Ruan Keyue, Liu Shang, Geng Wei, Gao Xu, Chen Huiling, Han Tiyun
Nanjing Chengshi (TheraRNA) Biomedical Technology Co., Ltd., Nanjing 210000, China.
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
Vaccines (Basel). 2025 Jun 26;13(7):691. doi: 10.3390/vaccines13070691.
: Bovine viral diarrhea virus (BVDV) causes significant economic losses in the cattle industry worldwide. The current vaccines have limited efficacy against diverse BVDV genotypes. Currently, multi-antigen target design and nanocarrier display technologies can provide ideas for broad-spectrum and efficient BVDV vaccine design. : Here we developed a trivalent mRNA vaccine encoding the domains I-II of envelope glycoprotein E2 from three BVDV genotypes (3E2), introduced with bovine IgG1 Fc (bFc), STABILON (hStab), and artificial virus-like particle (ARVLP) containing CD80 transmembrane (TM) domain, FcγRII cytoplasmic domain, and WW domain of ITCH. Then, in vitro expression, in vivo immunogenicity and neutralizing antibody analysis were performed to evaluate the vaccines. : The in vitro expression results showed that bFc and hStab dramatically enhanced antigen expression and immunogenicity. In addition, the ARVLP further enhanced the secretion and potency of neutralizing antibodies. Finally, the immunogenicity of the bFc_BVDV_3E2_ARVLP_hStab mRNA vaccine was evaluated in mice, guinea pigs, and lactating goats and high levels of neutralizing antibodies against all three BVDV genotypes were detected. : Our trivalent design strategy with bFc, hStab, and ARVLP shows highly efficient expression as well as strong immunogenicity and provides a promising approach for next-generation BVDV vaccines with broader and stronger protection.
牛病毒性腹泻病毒（BVDV）在全球养牛业中造成重大经济损失。目前的疫苗对多种BVDV基因型的效力有限。目前，多抗原靶点设计和纳米载体展示技术可为广谱高效的BVDV疫苗设计提供思路。
在此，我们开发了一种三价mRNA疫苗，其编码来自三种BVDV基因型的包膜糖蛋白E2的I-II结构域（3E2），引入了牛IgG1 Fc（bFc）、STABILON（hStab）以及包含CD80跨膜（TM）结构域、FcγRII胞质结构域和ITCH的WW结构域的人工病毒样颗粒（ARVLP）。然后，进行体外表达、体内免疫原性和中和抗体分析以评估该疫苗。
体外表达结果表明，bFc和hStab显著增强了抗原表达和免疫原性。此外，ARVLP进一步增强了中和抗体的分泌和效力。最后，在小鼠、豚鼠和泌乳山羊中评估了bFc_BVDV_3E2_ARVLP_hStab mRNA疫苗的免疫原性，并检测到针对所有三种BVDV基因型的高水平中和抗体。
我们采用bFc、hStab和ARVLP的三价设计策略显示出高效表达以及强大的免疫原性，并为具有更广泛、更强保护作用的下一代BVDV疫苗提供了一种有前景的方法。
