Hsueh Fu-Chun, Chang Yen-Chen, Kao Chi-Fei, Hsu Chin-Wei, Chang Hui-Wen
Graduate Institute of Molecular and Comparative Pathobiology, School of Veterinary Medicine, National Taiwan University, Taipei 10617, Taiwan.
School of Veterinary Medicine, National Taiwan University, Taipei 10617, Taiwan.
Vaccines (Basel). 2020 Feb 24;8(1):102. doi: 10.3390/vaccines8010102.
Intramuscular (IM) immunization is generally considered incapable of generating a protective mucosal immune response. In the swine industry, attempts to develop a safe and protective vaccine for controlling porcine epidemic diarrhea (PED) via an IM route of administration have been unsuccessful. In the present study, porcine chemokine ligand proteins CCL25, 27, and 28 were constructed and stably expressed in the mammalian expression system. IM co-administration of inactivated PEDV (iPEDV) particles with different CC chemokines and Freund's adjuvants resulted in recruiting CCR9+ and/or CCR10+ inflammatory cells to the injection site, thereby inducing superior systemic PEDV specific IgG, fecal IgA, and viral neutralizing antibodies in pigs. Moreover, pigs immunized with iPEDV in combination with CCL25 and CCL28 elicited substantial protection against a virulent PEDV challenge. We show that the porcine CC chemokines could be novel adjuvants for developing IM vaccines for modulating mucosal immune responses against mucosal transmissible pathogens in pigs.
肌肉注射(IM)免疫通常被认为无法产生保护性黏膜免疫反应。在养猪业中,试图通过肌肉注射途径开发一种安全且具有保护性的疫苗来控制猪流行性腹泻(PED)的尝试均未成功。在本研究中,构建了猪趋化因子配体蛋白CCL25、27和28,并在哺乳动物表达系统中稳定表达。将灭活的猪流行性腹泻病毒(iPEDV)颗粒与不同的CC趋化因子和弗氏佐剂进行肌肉联合注射,导致CCR9 +和/或CCR10 +炎性细胞募集到注射部位,从而在猪体内诱导产生更高水平的全身性PEDV特异性IgG、粪便IgA和病毒中和抗体。此外,用iPEDV与CCL25和CCL28联合免疫的猪对强毒PEDV攻击产生了实质性的保护作用。我们表明,猪CC趋化因子可能是开发肌肉注射疫苗的新型佐剂,用于调节猪针对黏膜传播病原体的黏膜免疫反应。