Goksøyr Louise, Skrzypczak Magdalena, Sampson Maureen, Nielsen Morten A, Salanti Ali, Theander Thor G, Remaley Alan T, De Jongh Willem A, Sander Adam F
Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
AdaptVac Aps, 2200 Copenhagen, Denmark.
Vaccines (Basel). 2022 Dec 20;11(1):2. doi: 10.3390/vaccines11010002.
Administration of PCSK9-specific monoclonal antibodies, as well as peptide-based PCSK9 vaccines, can lower plasma LDL cholesterol by blocking PCSK9. However, these treatments also cause an increase in plasma PCSK9 levels, presumably due to the formation of immune complexes. Here, we utilize a versatile capsid virus-like particle (cVLP)-based vaccine platform to deliver both full-length (FL) PCSK9 and PCSK9-derived peptide antigens, to investigate whether induction of a broader polyclonal anti-PCSK9 antibody response would mediate more efficient clearance of plasma PCSK9. This head-to-head immunization study reveals a significantly increased capacity of the FL PCSK9 cVLP vaccine to opsonize and clear plasma PCSK9. These findings may have implications for the design of PCSK9 and other vaccines that should effectively mediate opsonization and immune clearance of target antigens.
给予抗PCSK9特异性单克隆抗体以及基于肽的PCSK9疫苗，可通过阻断PCSK9来降低血浆低密度脂蛋白胆固醇。然而，这些治疗也会导致血浆PCSK9水平升高，推测是由于免疫复合物的形成。在此，我们利用一种通用的基于衣壳病毒样颗粒（cVLP）的疫苗平台来递送全长（FL）PCSK9和源自PCSK9的肽抗原，以研究诱导更广泛的多克隆抗PCSK9抗体反应是否会介导血浆PCSK9更有效的清除。这项直接比较的免疫研究表明，FL PCSK9 cVLP疫苗调理和清除血浆PCSK9的能力显著增强。这些发现可能对PCSK9及其他应有效介导靶抗原调理和免疫清除的疫苗的设计具有启示意义。
