Elicio Therapeutics, One Kendall Square, Suite 14303, Cambridge, MA 02139, USA.
Sci Adv. 2021 Feb 5;7(6). doi: 10.1126/sciadv.abe5819. Print 2021 Feb.
The profound consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mandate urgent development of effective vaccines. Here, we evaluated an Amphiphile (AMP) vaccine adjuvant, AMP-CpG, composed of diacyl lipid-modified CpG, admixed with the SARS-CoV-2 Spike-2 receptor binding domain protein as a candidate vaccine (ELI-005) in mice. AMP modification efficiently delivers CpG to lymph nodes, where innate and adaptive immune responses are generated. Compared to alum, immunization with AMP-CpG induced >25-fold higher antigen-specific T cells that produced multiple T helper 1 (T1) cytokines and trafficked into lung parenchyma. Antibody responses favored T1 isotypes (IgG2c and IgG3) and potently neutralized Spike-2-ACE2 receptor binding, with titers 265-fold higher than natural convalescent patient COVID-19 responses; T cell and antibody responses were maintained despite 10-fold dose reduction in Spike antigen. Both cellular and humoral immune responses were preserved in aged mice. These advantages merit clinical translation to SARS-CoV-2 and other protein subunit vaccines.
严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的深远影响要求迫切开发有效的疫苗。在这里，我们评估了 Amphiphile (AMP) 疫苗佐剂 AMP-CpG，其由二酰基脂质修饰的 CpG 组成，与 SARS-CoV-2 Spike-2 受体结合域蛋白混合作为候选疫苗 (ELI-005) 在小鼠中。AMP 修饰可有效地将 CpG 递送至淋巴结，在那里产生先天和适应性免疫反应。与铝佐剂相比，用 AMP-CpG 免疫诱导的抗原特异性 T 细胞高 25 倍以上，这些 T 细胞产生多种 T 辅助 1 (T1) 细胞因子，并迁移到肺实质中。抗体反应有利于 T1 同型 (IgG2c 和 IgG3)，并能有效地中和 Spike-2-ACE2 受体结合，其滴度比自然康复的 COVID-19 患者高 265 倍;尽管 Spike 抗原的剂量减少了 10 倍，但 T 细胞和抗体反应仍得以维持。在老年小鼠中，细胞和体液免疫反应均得以保留。这些优势值得将其用于 SARS-CoV-2 和其他蛋白质亚单位疫苗的临床转化。
