Key result
CF501/RBD-Fc vaccine induces potent broad-neutralizing antibodies against Omicron subvariants in rhesus macaques.
Why the study?
The recently emerged Omicron subvariants XBB and BQ.1.1 exhibit striking immune evasion against most monoclonal neutralizing antibodies and convalescent plasma, necessitating broad-spectrum COVID-19 vaccines.
Does CF501/RBD-Fc vaccine induce broad-neutralizing antibodies against SARS-CoV-2 Omicron subvariants in rhesus macaques?
Does CF501/RBD-Fc vaccine induce broad-neutralizing antibodies against SARS-CoV-2 Omicron subvariants in rhesus macaques?
A pan-sarbecovirus vaccine based on the original SARS-CoV-2 RBD and a STING agonist adjuvant elicits potent neutralizing antibodies against Omicron subvariants in non-human primates.
Supports preclinical pan-sarbecovirus vaccine development; leaves open human translation against evolving Omicron variants.
The recently emerged Omicron subvariants XBB and BQ.1.1 have presented striking immune evasion against most monoclonal neutralizing antibodies and convalescent plasma. Therefore, it is essential to develop broad-spectrum COVID-19 vaccines to combat current and future emerging variants. Here, we found that the human IgG Fc-conjugated RBD of the original SARS-CoV-2 strain (WA1) plus a novel STING agonist-based adjuvant CF501 (CF501/RBD-Fc) could induce highly potent and durable broad-neutralizing antibody (bnAb) responses against Omicron subvariants, including BQ.1.1 and XBB in rhesus macaques with NT50s ranging from 2,118 to 61,742 after three doses. A decline of 0.9- to 4.7-fold was observed in the neutralization activity of sera in the CF501/RBD-Fc group against BA.2.2, BA.2.9, BA.5, BA.2.75, and BF.7 relative to D614G after three doses, while a significant decline of NT50 against BQ.1.1 (26.9-fold) and XBB (22.5-fold) relative to D614G. However, the bnAbs were still effective in neutralizing BQ.1.1 and XBB infection. These results suggest that the conservative but nondominant epitopes in RBD could be stimulated by CF501 to generate bnAbs, providing a proof-of-concept for using "nonchangeable against changeables" strategy to develop pan-sarbecovirus vaccines against sarbecoviruses, including SARS-CoV-2 and its variants.
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Liu et al. (2023) studied COVID-19. CF501/RBD-Fc vaccine was evaluated on Neutralizing antibody responses (NT50s) against Omicron subvariants. The CF501/RBD-Fc vaccine induced potent broad-neutralizing antibody responses against Omicron subvariants BQ.1.1 and XBB in rhesus macaques, with NT50s ranging from 2,118 to 61,742.
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