Amirabad Virology Laboratory, Vaccine Unit, Tehran 1413693341, Iran.
Department of Microbiology, Faculty Science, Jahrom Branch, Islamic Azad University, Jahrom, Iran.
Virus Res. 2022 Oct 2;319:198857. doi: 10.1016/j.virusres.2022.198857. Epub 2022 Jul 9.
With the COVID-19 pandemic globally, the ongoing threat of new challenges of mucosal infections was once again reminded human beings. Hence, access to the next-generation vaccine to elicit mucosal immunity is required to reduce virus shedding. SARS-CoV-2 retains a unique polybasic cleavage motif in its spike protein, recognized by the host furin protease. The proteolytic furin cleavage site at the junction of S1/S2 glycoprotein plays a key role in the pathogenesis of SARS-CoV-2. Here, we examined the protective immunity of a double-deleted PRRA/GTNGTKR motifs cold-adapted live-attenuated candidate vaccines as a called "KaraVac." using a hamster animal model of infected attenuated SARS-CoV-2. The KaraVac vaccinated hamsters were challenged against the wild-type (WT) SARS-CoV-2. No apparent bodyweight loss and histopathological lesions were observed in the hamsters. The establishment of sterilizing immunity was induced via stimulating a robust neutralizing antibody (NAb) response in a hamster model. Consequently, deletions in the spike sequence and inoculation into hamsters provide resistance to the subsequent challenge with WT SARS-CoV-2. We have suggested that deletion of the furin cleavage site and GTNGTKR motifs in the spike sequence attenuates the virus from the parental strain and can be used as a potent immunogen.
随着 COVID-19 大流行在全球范围内的肆虐，人们再次意识到新的粘膜感染挑战仍在持续。因此，需要获得新一代疫苗来引发粘膜免疫，以减少病毒脱落。SARS-CoV-2 在其刺突蛋白中保留了一个独特的多碱性切割基序，被宿主弗林蛋白酶识别。S1/S2 糖蛋白交界处的蛋白水解弗林切割位点在 SARS-CoV-2 的发病机制中起着关键作用。在这里，我们使用感染性减弱的 SARS-CoV-2 仓鼠动物模型，研究了一种称为“KaraVac”的双缺失 PRRA/GTNGTKR 基序冷适应活减毒候选疫苗的保护免疫作用。KaraVac 接种的仓鼠在受到野生型（WT）SARS-CoV-2 攻击时没有明显的体重减轻和组织病理学损伤。在仓鼠模型中，通过刺激强烈的中和抗体（NAb）反应建立了杀菌免疫。因此，刺突序列中的缺失和接种到仓鼠体内提供了对随后 WT SARS-CoV-2 攻击的抵抗力。我们已经表明，刺突序列中弗林切割位点和 GTNGTKR 基序的缺失使病毒从亲代株减弱，并可用作有效的免疫原。
