Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, School of Pharmacy, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, School of Pharmacy, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Cell Rep Med. 2024 Mar 19;5(3):101445. doi: 10.1016/j.xcrm.2024.101445. Epub 2024 Feb 29.
The emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants BA.2.86 and JN.1 raise concerns regarding their potential to evade immune surveillance and spread globally. Here, we test sera from rhesus macaques immunized with 3 doses of wild-type SARS-CoV-2 receptor-binding domain (RBD)-Fc adjuvanted with the STING agonist CF501. We find that the sera can potently neutralize pseudotyped XBB.1.5, XBB.1.16, CH.1.1, EG.5, BA.2.86, and JN.1, with 50% neutralization titers ranging from 3,494 to 7,424. We also demonstrate that CF501, but not Alum, can enhance immunogenicity of the RBD from wild-type SARS-CoV-2 to improve induction of broadly neutralizing antibodies (bnAbs) with binding specificity and activity similar to those of SA55, BN03, and S309, thus exhibiting extraordinary broad-spectrum neutralizing activity. Overall, the RBD from wild-type SARS-CoV-2 also contains conservative epitopes. The RBD-Fc adjuvanted by CF501 can elicit potent bnAbs against JN.1, BA.2.86, and other XBB subvariants. This strategy can be adopted to develop broad-spectrum vaccines to combat future emerging and reemerging viral infectious diseases.
新兴的严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）奥密克戎亚变种 BA.2.86 和 JN.1 引起了人们对其逃避免疫监视并在全球传播的能力的关注。在这里，我们测试了用 3 剂野生型 SARS-CoV-2 受体结合域（RBD）-Fc 免疫恒河猴的血清，该 RBD-Fc 用 STING 激动剂 CF501 佐剂。我们发现，这些血清可以有效地中和假型 XBB.1.5、XBB.1.16、CH.1.1、EG.5、BA.2.86 和 JN.1，其 50%中和效价范围为 3,494 至 7,424。我们还证明，CF501 而不是 Alum 可以增强野生型 SARS-CoV-2 的 RBD 的免疫原性，从而提高对广泛中和抗体（bnAbs）的诱导，这些 bnAbs 具有与 SA55、BN03 和 S309 相似的结合特异性和活性，因此表现出非凡的广谱中和活性。总体而言，野生型 SARS-CoV-2 的 RBD 也含有保守表位。CF501 佐剂的 RBD-Fc 可以引发针对 JN.1、BA.2.86 和其他 XBB 亚变种的强大 bnAbs。该策略可用于开发广谱疫苗以应对未来新发和再发的病毒性传染病。
