Balasubramaniyam Arasu, Ryan Emma, Brown Dallas, Hamza Therwa, Harrison William, Gan Michael, Sankhala Rajeshwer S, Chen Wei-Hung, Martinez Elizabeth J, Jensen Jaime L, Dussupt Vincent, Mendez-Rivera Letzibeth, Mayer Sandra, King Jocelyn, Michael Nelson L, Regules Jason, Krebs Shelly, Rao Mangala, Matyas Gary R, Joyce M Gordon, Batchelor Adrian H, Gromowski Gregory D, Dutta Sheetij
Biologics Research and Development Branch, Structural Vaccinology Laboratory, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Vaccines (Basel). 2022 Dec 25;11(1):42. doi: 10.3390/vaccines11010042.
The emergence of novel potentially pandemic pathogens necessitates the rapid manufacture and deployment of effective, stable, and locally manufacturable vaccines on a global scale. In this study, the ability of the expression system to produce the receptor binding domain (RBD) of the SARS-CoV-2 spike protein was evaluated. The RBD of the original Wuhan-Hu1 variant and of the Alpha and Beta variants of concern (VoC) were expressed in , and their biochemical and immunological profiles were compared to RBD produced in mammalian cells. The -produced RBD variants recapitulated the structural character of mammalian-expressed RBD and bound to human angiotensin converting enzyme (ACE2) receptor and a panel of neutralizing SARS-CoV-2 monoclonal antibodies. A pilot vaccination in mice with bacterial RBDs formulated with a novel liposomal adjuvant, Army Liposomal Formulation containing QS21 (ALFQ), induced polyclonal antibodies that inhibited RBD association to ACE2 in vitro and potently neutralized homologous and heterologous SARS-CoV-2 pseudoviruses. Although all vaccines induced neutralization of the non-vaccine Delta variant, only the Beta RBD vaccine produced in and mammalian cells effectively neutralized the Omicron BA.1 pseudovirus. These outcomes warrant further exploration of as an expression platform for non-glycosylated, soluble immunogens for future rapid response to emerging pandemic pathogens.
新型潜在大流行病原体的出现使得有必要在全球范围内快速生产和部署有效、稳定且可在当地生产的疫苗。在本研究中，评估了该表达系统生产严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白受体结合域（RBD）的能力。原始武汉-胡1变体以及关注的阿尔法和贝塔变异株（VoC）的RBD在[具体表达系统]中表达，并将其生化和免疫学特征与在哺乳动物细胞中产生的RBD进行比较。[具体表达系统]产生的RBD变体概括了哺乳动物表达的RBD的结构特征，并与人类血管紧张素转换酶（ACE2）受体以及一组中和SARS-CoV-2单克隆抗体结合。用含有QS21的新型脂质体佐剂陆军脂质体配方（ALFQ）配制的细菌RBD对小鼠进行的初步疫苗接种诱导了多克隆抗体，这些抗体在体外抑制RBD与ACE2的结合，并有效中和同源和异源SARS-CoV-2假病毒。尽管所有疫苗都诱导了对非疫苗德尔塔变异株的中和作用，但只有在[具体表达系统]和哺乳动物细胞中产生的贝塔RBD疫苗有效中和了奥密克戎BA.1假病毒。这些结果值得进一步探索[具体表达系统]作为非糖基化可溶性免疫原的表达平台，以便未来对新出现的大流行病原体做出快速反应。
