Icosagen Cell Factory OÜ, Õssu, Kambja vald, Tartumaa, Estonia.
Institute of Technology, University of Tartu, Tartu, Estonia.
PLoS One. 2022 Jun 10;17(6):e0268806. doi: 10.1371/journal.pone.0268806. eCollection 2022.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to impose a serious burden on health systems globally. Despite worldwide vaccination, social distancing and wearing masks, the spread of the virus is ongoing. One of the mechanisms by which neutralizing antibodies (NAbs) block virus entry into cells encompasses interaction inhibition between the cell surface receptor angiotensin-converting enzyme 2 (ACE2) and the spike (S) protein of SARS-CoV-2. SARS-CoV-2-specific NAb development can be induced in the blood of cattle. Pregnant cows produce NAbs upon immunization, and antibodies move into the colostrum immediately before calving. Here, we immunized cows with SARS-CoV-2 S1 receptor binding domain (RBD) protein in proper adjuvant solutions, followed by one boost with SARS-CoV-2 trimeric S protein and purified immunoglobulins from colostrum. We demonstrate that this preparation indeed blocks the interaction between the trimeric S protein and ACE2 in different in vitro assays. Moreover, we describe the formulation of purified immunoglobulin preparation into a nasal spray. When administered to human subjects, the formulation persisted on the nasal mucosa for at least 4 hours, as determined by a clinical study. Therefore, we are presenting a solution that shows great potential to serve as a prophylactic agent against SARS-CoV-2 infection as an additional measure to vaccination and wearing masks. Moreover, our technology allows for rapid and versatile adaptation for preparing prophylactic treatments against other diseases using the defined characteristics of antibody movement into the colostrum.
严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)继续在全球范围内对卫生系统造成严重负担。尽管全球范围内进行了疫苗接种、保持社交距离和佩戴口罩,病毒仍在传播。中和抗体(NAb)阻止病毒进入细胞的机制之一包括血管紧张素转换酶 2(ACE2)和 SARS-CoV-2 的刺突(S)蛋白之间的相互作用抑制。牛的血液中可以产生 SARS-CoV-2 特异性 NAb。免疫接种后,怀孕的奶牛会产生 NAb,并且抗体在分娩前立即进入初乳。在这里,我们用 SARS-CoV-2 S1 受体结合域(RBD)蛋白在适当的佐剂溶液中对奶牛进行免疫接种,然后用 SARS-CoV-2 三聚体 S 蛋白和初乳中的纯化免疫球蛋白进行一次加强免疫。我们证明该制剂确实可以在不同的体外测定中阻断三聚体 S 蛋白与 ACE2 之间的相互作用。此外,我们还描述了将纯化免疫球蛋白制剂制成鼻腔喷雾剂的方法。当将该制剂施用于人体受试者时,通过临床研究确定,该制剂在鼻黏膜上至少保持 4 小时。因此,我们提出了一种很有潜力的解决方案,作为接种疫苗和佩戴口罩的额外措施,作为预防 SARS-CoV-2 感染的预防性药物。此外,我们的技术允许使用抗体进入初乳的定义特征,快速灵活地适应针对其他疾病的预防性治疗。