Feldman Peter A
Research Unit, Queen's House Consulting, HealthAid House, Marlborough Road, Harrow, Middlesex HA1 1UD, UK.
Med Hypotheses. 2022 Feb;159:110756. doi: 10.1016/j.mehy.2021.110756. Epub 2022 Jan 3.
Administration of AstraZeneca/Oxford and Johnson & Johnson/Janssen Covid-19 vaccines which use an adenovirus vector for DNA delivery has been associated with very rare thromboembolic complications coupled with an immune response to platelet factor 4 protein. The cause of this has not yet been identified. It is known that binding of coagulation factor proteins to the surface of some adenoviruses can protect their function. Here I propose that the thromboembolic events are caused by impairment of coagulation factor X binding to the virus capsid. The unprotected capsid then stimulates an immune response leading to platelet activation, increased thrombogenicity and formation of an antibody complex with platelet factor 4. Impaired binding of factor X may be due to an undiagnosed mutation in affected individuals. Options to test this mechanism experimentally and potential remedial actions to resolve the hazard are described. This mechanism offers a remedial route to address concerns about the safety of these vaccines, which are otherwise well-positioned to deliver global Covid-19 immunity across diverse healthcare economies.
使用腺病毒载体进行DNA递送的阿斯利康/牛津大学和强生/杨森新冠疫苗的接种与非常罕见的血栓栓塞并发症以及对血小板因子4蛋白的免疫反应有关。其原因尚未确定。已知凝血因子蛋白与某些腺病毒表面的结合可以保护其功能。在此我提出,血栓栓塞事件是由凝血因子X与病毒衣壳结合受损引起的。未受保护的衣壳随后刺激免疫反应,导致血小板活化、血栓形成增加以及与血小板因子4形成抗体复合物。因子X结合受损可能是由于受影响个体中未被诊断出的突变。文中描述了通过实验测试该机制的方法以及解决这一风险的潜在补救措施。这一机制为解决对这些疫苗安全性的担忧提供了一条补救途径,否则这些疫苗在为全球不同医疗体系提供新冠免疫力方面具有良好的前景。