National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Microbiol Spectr. 2024 Oct 3;12(10):e0069224. doi: 10.1128/spectrum.00692-24. Epub 2024 Aug 15.
Porcine epidemic diarrhea virus (PEDV) is an enteropathogenic coronavirus that causes substantial economic loss to the global pig industry. The emergence of PEDV variants has increased the need for new vaccines, as commercial vaccines confer inferior protection against currently circulating strains. It is well established that the induction of mucosal immunity is crucial for PEDV vaccines to provide better protection against PEDV infection. In this study, we constructed a recombinant adenovirus expressing the core neutralization epitope (COE) of G2b PEDV based on human adenovirus serotype 5 (Ad5). We evaluated the effects of different administration routes and doses of vaccine immunogenicity in Balb/c mice. Both intramuscular (IM) and intranasal (IN) administration elicited significant humoral responses, including COE-specific IgG in serum and mucosal secretions, along with serum-neutralizing antibodies. Moreover, IN delivery was more potent than IM in stimulating IgA in serum and mucosal samples and in dampening the immune response to the Ad5 vector. The immune response was stronger after high versus low dose IM injection, whereas no significant difference was observed between high and low IN doses. In summary, our findings provide important insights for developing novel PEDV vaccines.IMPORTANCEPorcine epidemic diarrhea (PED) is a highly contagious disease that has severe economic implications for the pork industry. Developing an effective vaccine against PEDV remains a necessity. Here, we generated a recombinant adenovirus vaccine based on Ad5 to express the COE protein of PEDV (rAd5-PEDV-COE) and systematically evaluated the immunogenicity of the adenovirus-vectored vaccine using different administration routes (intramuscular and intranasal) and doses in a mouse model. Our results show that rAd5-PEDV-COE induced potent systemic humoral response regardless of the dose or immunization route. Notably, intranasal delivery was superior to induce peripheral and mucosal IgA antibodies compared with intramuscular injection. Our data provide valuable insights into designing novel PEDV vaccines.
猪流行性腹泻病毒（PEDV）是一种肠致病性冠状病毒，它给全球养猪业造成了巨大的经济损失。PEDV 变异株的出现增加了对新型疫苗的需求，因为商业疫苗对目前流行的毒株的保护效果较差。已经证实，诱导黏膜免疫对于 PEDV 疫苗提供更好的 PEDV 感染保护至关重要。在本研究中，我们基于人腺病毒血清型 5（Ad5）构建了表达 G2b PEDV 核心中和表位（COE）的重组腺病毒。我们评估了不同疫苗接种途径和剂量对 Balb/c 小鼠免疫原性的影响。肌肉内（IM）和鼻内（IN）接种均引起了显著的体液免疫反应，包括血清和黏膜分泌物中的 COE 特异性 IgG，以及血清中和抗体。此外，与 IM 相比，IN 给药更能刺激血清和黏膜样本中的 IgA，并抑制对 Ad5 载体的免疫反应。高剂量 IM 注射后的免疫反应更强，而高剂量和低剂量 IN 之间没有观察到显著差异。总之，我们的研究结果为开发新型 PEDV 疫苗提供了重要的见解。
猪流行性腹泻（PED）是一种高度传染性疾病，对养猪业造成了严重的经济影响。开发针对 PEDV 的有效疫苗仍然是必要的。在这里，我们基于 Ad5 生成了一种表达 PEDV COE 蛋白的重组腺病毒疫苗（rAd5-PEDV-COE），并在小鼠模型中系统地评估了不同接种途径（肌肉内和鼻内）和剂量对腺病毒载体疫苗的免疫原性。我们的结果表明，rAd5-PEDV-COE 诱导了强大的系统体液免疫反应，无论剂量或免疫途径如何。值得注意的是，与肌肉内注射相比，鼻内给药更能诱导外周和黏膜 IgA 抗体。我们的数据为设计新型 PEDV 疫苗提供了有价值的见解。
