tetano
Editor, Senior Moderator
Cell Rep Med
. 2024 Feb 23:101445.
doi: 10.1016/j.xcrm.2024.101445. Online ahead of print. Neutralization of SARS-CoV-2 BA.2.86 and JN.1 by CF501 adjuvant-enhanced immune responses targeting the conserved epitopes in ancestral RBD
Zezhong Liu[SUP] 1 [/SUP], Jie Zhou[SUP] 2 [/SUP], Weijie Wang[SUP] 2 [/SUP], Guangxu Zhang[SUP] 2 [/SUP], Lixiao Xing[SUP] 2 [/SUP], Keqiang Zhang[SUP] 2 [/SUP], Yuanzhou Wang[SUP] 2 [/SUP], Wei Xu[SUP] 2 [/SUP], Qian Wang[SUP] 2 [/SUP], Qiuhong Man[SUP] 3 [/SUP], Qiao Wang[SUP] 2 [/SUP], Tianlei Ying[SUP] 2 [/SUP], Yun Zhu[SUP] 4 [/SUP], Shibo Jiang[SUP] 5 [/SUP], Lu Lu[SUP] 6 [/SUP]
Affiliations
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.
Keywords: JN.1; SARS-CoV-2; STING agonist; adjuvant; conserved epitopes; coronavirus; vaccine.
. 2024 Feb 23:101445.
doi: 10.1016/j.xcrm.2024.101445. Online ahead of print. Neutralization of SARS-CoV-2 BA.2.86 and JN.1 by CF501 adjuvant-enhanced immune responses targeting the conserved epitopes in ancestral RBD
Zezhong Liu[SUP] 1 [/SUP], Jie Zhou[SUP] 2 [/SUP], Weijie Wang[SUP] 2 [/SUP], Guangxu Zhang[SUP] 2 [/SUP], Lixiao Xing[SUP] 2 [/SUP], Keqiang Zhang[SUP] 2 [/SUP], Yuanzhou Wang[SUP] 2 [/SUP], Wei Xu[SUP] 2 [/SUP], Qian Wang[SUP] 2 [/SUP], Qiuhong Man[SUP] 3 [/SUP], Qiao Wang[SUP] 2 [/SUP], Tianlei Ying[SUP] 2 [/SUP], Yun Zhu[SUP] 4 [/SUP], Shibo Jiang[SUP] 5 [/SUP], Lu Lu[SUP] 6 [/SUP]
Affiliations
- PMID: 38428429
- DOI: 10.1016/j.xcrm.2024.101445
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.
Keywords: JN.1; SARS-CoV-2; STING agonist; adjuvant; conserved epitopes; coronavirus; vaccine.