SARS-CoV-2 Omicron BA.2.86: less neutralization evasion compared to XBB sub-variants (preprint)

The continual emergence and circulation of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have caused a great challenge for the coronavirus disease 2019 (COVID-19) pandemic control. Recently, Omicron BA.2.86 was identified with more than 30 amino acid changes on the spike (S) protein, compared to Omicron BA.2 or XBB.1.5. The immune evasion potential of BA.2.86 is of great concern. In this study, we evaluated the neutralizing activities of sera collected from participants and mice. Participants were divided into five groups according to their vaccination (inactivated vaccine, protein subunit vaccine ZF2001 or ZF2202-A) and infection (Omicron BF.7/BA.5.2) status. ZF2202-A is ZF2001 vaccine's next-generation COVID-19 vaccine with updated bivalent Delta-BA.5 RBD-heterodimer immunogen. BALB/c mice were immunized with XBB.1.5 RBD-homodimer, BA.5-BA.2, Delta-XBB.1.5 or BQ.1.1-XBB.1.5 RBD-heterodimers protein vaccine candidates for evaluating the neutralizing responses. We found that Omicron BA.2.86 shows stronger immune evasion than BA.2 due to >30 additional mutations on S protein. Compared to XBB sub-variants, BA.2.86 does not display more resistance to the neutralizing responses induced by ZF2001-vaccination, BF.7/BA.5.2 breakthrough infection or a booster dose of ZF2202-A-vaccination. In addition, the mouse experiment results showed that BQ.1.1-XBB.1.5 RBD-heterodimer and XBB.1.5 RBD-homodimer induced high neutralizing responses against XBB sub-variants and BA.2.86, indicating that next-generation COVID-19 vaccine should be developed to enhance the protection efficacy against the circulating strains in the future.

Neutralization of SARS-CoV-2 EG.5/EG.5.1 by sera from ZF2001 RBD-dimer and its next-generation vaccines (preprint)

SARS-CoV-2 Omicron EG.5 and EG.5.1 are surging in several areas of the world, including China. Compared with XBB.1, EG.5 contains additional mutations of F456L and S486P in the spike protein receptor binding domain (RBD) and its subvariant EG.5.1 carries a further spike mutation Q52H. The immune escape potential of EG.5/EG.5.1 is of great concern. In this study, we evaluated the neutralization activities of sera from participants who received COVID-19 inactivated vaccines, protein subunit vaccine ZF2001 or a booster vaccination of Delta-BA.5 RBD-heterodimer protein vaccine, and participants who had a breakthrough infection during a wave of BF.7/BA.5.2 circulation in December 2022. Neutralization profiles elicited by bivalent RBD-heterodimer vaccine candidates containing XBB.1.5 antigen were evaluated in a murine model. We found that EG.5 and EG.5.1 displayed similar immune evasion potential to XBB.1 and XBB.1.5. The Delta-BA.5 RBD-heterodimer booster induced higher neutralizing titers against the tested XBB subvariants, including EG.5 and EG.5.1, than breakthrough infection by BF.7 or BA.5.2. In addition, Delta-XBB.1.5 and BQ.1.1-XBB.1.5 RBD-heterodimer vaccines induced high neutralizing activities against XBB sub-variants in a murine model, suggesting that next-generation COVID-19 vaccines with updated components must be developed to enhance the protection efficacy against the circulating SARS-CoV-2 strains.