Rodrigues Kristen A, Rodriguez-Aponte Sergio A, Dalvie Neil C, Lee Jeong Hyun, Abraham Wuhbet, Carnathan Diane G, Jimenez Luis E, Ngo Julia T, Chang Jason Y H, Zhang Zeli, Yu Jingyou, Chang Aiquan, Nakao Catherine, Goodwin Benjamin, Naranjo Christopher A, Zhang Libin, Silva Murillo, Barouch Dan H, Silvestri Guido, Crotty Shane, Love J Christopher, Irvine Darrell J
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Harvard-MIT Health Sciences and Technology Program, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Sci Adv. 2021 Dec 10;7(50):eabj6538. doi: 10.1126/sciadv.abj6538. Epub 2021 Dec 8.
There is a need for additional rapidly scalable, low-cost vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to achieve global vaccination. Aluminum hydroxide (alum) adjuvant is the most widely available vaccine adjuvant but elicits modest humoral responses. We hypothesized that phosphate-mediated coanchoring of the receptor binding domain (RBD) of SARS-CoV-2 together with molecular adjuvants on alum particles could potentiate humoral immunity by promoting extended vaccine kinetics and codelivery of vaccine components to lymph nodes. Modification of RBD immunogens with phosphoserine (pSer) peptides enabled efficient alum binding and slowed antigen clearance, leading to notable increases in germinal center responses and neutralizing antibody titers in mice. Adding phosphate-containing CpG or saponin adjuvants to pSer-RBD:alum immunizations synergistically enhanced vaccine immunogenicity in mice and rhesus macaques, inducing neutralizing responses against SARS-CoV-2 variants. Thus, phosphate-mediated coanchoring of RBD and molecular adjuvants to alum is an effective strategy to enhance the efficacy of SARS-CoV-2 subunit vaccines.
为实现全球疫苗接种，需要额外的快速可扩展、低成本的抗严重急性呼吸综合征冠状病毒2（SARS-CoV-2）疫苗。氢氧化铝（明矾）佐剂是最广泛使用的疫苗佐剂，但引发的体液反应较弱。我们假设，通过促进疫苗动力学延长和疫苗成分向淋巴结的共递送，将SARS-CoV-2受体结合域（RBD）与分子佐剂在明矾颗粒上进行磷酸盐介导的共锚定，可以增强体液免疫。用磷酸丝氨酸（pSer）肽修饰RBD免疫原能够实现与明矾的有效结合并减缓抗原清除，导致小鼠生发中心反应和中和抗体滴度显著增加。在pSer-RBD：明矾免疫中添加含磷酸盐的CpG或皂苷佐剂可协同增强小鼠和恒河猴的疫苗免疫原性，诱导针对SARS-CoV-2变体的中和反应。因此，将RBD和分子佐剂通过磷酸盐介导共锚定到明矾上是提高SARS-CoV-2亚单位疫苗效力的有效策略。
N Engl J Med. 2021-4-29
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