Santana-Mederos Darielys, Perez-Nicado Rocmira, Climent Yanet, Rodriguez Laura, Ramirez Belinda Sanchez, Perez-Rodriguez Sonia, Rodriguez Meybi, Labrada Claudia, Hernandez Tays, Diaz Marianniz, Orosa Ivette, Ramirez Ubel, Oliva Reynaldo, Garrido Raine, Cardoso Felix, Landys Mario, Martinez Roselyn, Gonzalez Humberto, Hernandez Tamara, Ochoa-Azze Rolando, Perez Jose L, Enriquez Juliet, Gonzalez Nibaldo, Infante Yenicet, Espinosa Luis A, Ramos Yassel, González Luis Javier, Valenzuela Carmen, Casadesus Ana Victoria, Fernandez Briandy, Rojas Gertrudis, Pérez-Massón Beatriz, Tundidor Yaima, Bermudez Ernesto, Plasencia Claudia A, Boggiano Tammy, Ojito Eduardo, Chiodo Fabrizio, Fernandez Sonsire, Paquet Françoise, Fang Cheng, Chen Guang-Wu, Rivera Daniel G, Valdes-Balbin Yury, Garcia-Rivera Dagmar, Verez Bencomo Vicente
Finlay Vaccine Institute 200 and 21 Street Havana 11600 Cuba
Center of Molecular Immunology P.O. Box 16040 216 St. Havana Cuba.
RSC Chem Biol. 2021 Dec 8;3(2):242-249. doi: 10.1039/d1cb00200g. eCollection 2022 Feb 9.
SARS-CoV-2 infection is mediated by the interaction of the spike glycoprotein trimer its receptor-binding domain (RBD) with the host's cellular receptor. Vaccines seek to block this interaction by eliciting neutralizing antibodies, most of which are directed toward the RBD. Many protein subunit vaccines require powerful adjuvants to generate a potent antibody response. Here, we report on the use of a SARS-CoV-2 dimeric recombinant RBD combined with outer membrane vesicles (OMVs), adsorbed on alum, as a promising COVID-19 vaccine candidate. This formulation induces a potent and neutralizing immune response in laboratory animals, which is higher than that of the dimeric RBD alone adsorbed on alum. Sera of people vaccinated with this vaccine candidate, named Soberana01, show a high inhibition level of the RBD-ACE2 interaction using RBD mutants corresponding to SARS-CoV-2 variants of concern and wild-type expressed using the phage display technology. To our knowledge, this is the first time that the immunostimulation effect of OMVs is evaluated in vaccine candidates against SARS-CoV-2.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染是由刺突糖蛋白三聚体及其受体结合结构域（RBD）与宿主细胞受体相互作用介导的。疫苗试图通过引发中和抗体来阻断这种相互作用，其中大多数中和抗体都针对RBD。许多蛋白质亚单位疫苗需要强大的佐剂来产生有效的抗体反应。在此，我们报告了一种结合了外膜囊泡（OMV）的SARS-CoV-2二聚体重组RBD的应用，该RBD吸附在明矾上，作为一种有前景的新型冠状病毒肺炎（COVID-19）疫苗候选物。这种制剂在实验动物中诱导出强大的中和免疫反应，高于单独吸附在明矾上的二聚体RBD所诱导的免疫反应。接种了这种名为Soberana01的疫苗候选物的人的血清，使用与SARS-CoV-2关注变体相对应的RBD突变体以及利用噬菌体展示技术表达的野生型，对RBD-血管紧张素转换酶2（ACE2）相互作用显示出高抑制水平。据我们所知，这是首次在针对SARS-CoV-2的疫苗候选物中评估OMV的免疫刺激作用。
