Liu Jiawen, Wang Tiantian, Ren Hongying, Liu Ruixi, Wang Qian, Wu Jun, Liu Bo
Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, China.
Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
Vaccines (Basel). 2025 May 20;13(5):543. doi: 10.3390/vaccines13050543.
(1) Background: The currently circulating variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits resistance to antibodies induced by vaccines. The World Health Organization recommended the use of monovalent XBB.1 sublineages (e.g., XBB.1.5) as an antigenic component in 2023. (2) Objective: In this study, we aimed to develop vaccines based on the XBB.1.5 receptor-binding domain (RBD) to combat the recently emerged SARS-CoV-2 XBB and JN.1 variants, as well as previously circulating variants. (3) Methods: Glycoengineered was utilized to produce a recombinant XBB.1.5 RBD protein with mammalian-like and fucose-free N-glycosylation. The XBB.1.5 RBD was mixed with Al(OH):CpG adjuvants to prepare monovalent vaccines. Thereafter, the XBB.1.5 RBD was mixed with the Beta (B.1.351), Delta (B.1.617.2), or Omicron (BA.2) RBDs (1:1 ratio), along with Al(OH):CpG, to prepare bivalent vaccines. BALB/c mice were immunized with the monovalent and bivalent vaccines. Neutralizing antibody titers were assessed via pseudovirus and authentic virus assays; humoral immune responses were analyzed by RBD-binding IgG subtypes. (4) Results: The monovalent vaccine induced higher neutralizing antibody titers against Delta, BA.2, XBB.1.5, and JN.1 compared to those in mice immunized solely with Al(OH):CpG, as demonstrated by pseudovirus virus assays. The XBB.1.5/Delta RBD and XBB.1.5/Beta RBD-based bivalent vaccines provided potent protection against the BA.2, XBB.1.5, JN.1, and KP.2 variants, as well as the previously circulating Delta and Beta variants. All monovalent and bivalent vaccines induced high levels of RBD-binding IgG (IgG1, IgG2a, IgG2b, and IgG3) antibodies in mice, suggesting that they elicited robust humoral immune responses. The serum samples from mice immunized with the XBB.1.5 RBD-based and XBB.1.5/Delta RBD-based vaccines could neutralize the authentic XBB.1.16 virus. (5) Conclusions: The XBB.1.5/Beta and XBB.1.5/Delta RBD-based bivalent vaccines are considered as potential candidates for broad-spectrum vaccines against SARS-CoV-2 variants.
（1）背景：目前正在传播的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体对疫苗诱导的抗体表现出抗性。世界卫生组织在2023年建议使用单价XBB.1亚谱系（如XBB.1.5）作为抗原成分。（2）目的：在本研究中，我们旨在开发基于XBB.1.5受体结合域（RBD）的疫苗，以对抗最近出现的SARS-CoV-2 XBB和JN.1变体以及先前传播的变体。（3）方法：利用糖基工程生产具有类似哺乳动物且无岩藻糖N-糖基化的重组XBB.1.5 RBD蛋白。将XBB.1.5 RBD与氢氧化铝：CpG佐剂混合制备单价疫苗。此后，将XBB.1.5 RBD与贝塔（B.1.351）、德尔塔（B.1.617.2）或奥密克戎（BA.2）RBD（1:1比例）以及氢氧化铝：CpG混合制备二价疫苗。用单价和二价疫苗免疫BALB/c小鼠。通过假病毒和真实病毒试验评估中和抗体滴度；通过RBD结合IgG亚型分析体液免疫反应。（4）结果：如假病毒试验所示，与仅用氢氧化铝：CpG免疫的小鼠相比，单价疫苗诱导出针对德尔塔、BA.2、XBB.1.5和JN.1的更高中和抗体滴度。基于XBB.1.5/德尔塔RBD和XBB.1.5/贝塔RBD的二价疫苗对BA.2、XBB.1.5、JN.1和KP.2变体以及先前传播的德尔塔和贝塔变体提供了有效的保护。所有单价和二价疫苗在小鼠中均诱导出高水平的RBD结合IgG（IgG1、IgG2a、IgG2b和IgG3）抗体，表明它们引发了强大的体液免疫反应。用基于XBB.1.5 RBD和基于XBB.1.5/德尔塔RBD的疫苗免疫的小鼠血清样本能够中和真实的XBB.1.16病毒。（5）结论：基于XBB.1.5/贝塔和XBB.1.5/德尔塔RBD的二价疫苗被认为是针对SARS-CoV-2变体的广谱疫苗的潜在候选者。
