Homologous or heterologous booster of inactivated vaccine reduces SARS-CoV-2 Omicron variant escape from neutralizing antibodies

Abstract

The massive and rapid transmission of SARS-CoV-2 has led to the emergence of several viral variants of concern (VOCs), with the most recent one, B.1.1.529 (Omicron), which accumulated a large number of spike mutations, raising the specter that this newly identified variant may escape from the currently available vaccines and therapeutic antibodies. Using VSV-based pseudovirus, we found that Omicron variant is markedly resistant to neutralization of sera from convalescents or individuals vaccinated by two doses of inactivated whole-virion vaccines (BBIBP-CorV). However, a homologous inactivated vaccine booster or a heterologous booster with protein subunit vaccine (ZF2001) significantly increased neutralization titers to both WT and Omicron variant. Moreover, at day 14 post the third dose, neutralizing antibody titer reduction for Omicron was less than that for convalescents or individuals who had only two doses of the vaccine, indicating that a homologous or heterologous booster can reduce the Omicron escape from neutralizing. In addition, we tested a panel of 17 SARS-CoV-2 monoclonal antibodies (mAbs). Omicron resists seven of eight authorized/approved mAbs, as well as most of the other mAbs targeting distinct epitopes on RBD and NTD. Taken together, our results suggest the urgency to push forward the booster vaccination to combat the emerging SARS-CoV-2 variants.

Emergence of SARS-CoV-2 Omicron (B.1.1.529) variant, salient features, high global health concerns and strategies to counter it amid ongoing COVID-19 pandemic

“…Among the 15 RDB mutation, K417N (a mutation common with beta variant), and E484A are the mutations that lead to overwhelmingly disruptive effects to many known antibodies ( Chen et al, 2021a ). The sera from the individuals vaccinated by two doses of inactivated whole-virion vaccines (BBIBP-CorV) showed reduced neutralization by Omicron, however homologous or heterologous vaccination with protein subunit vaccine (ZF 2001) enhance neutralization against the Omicron ( Wang et al, 2022 ). Homologous boosting with BBIBP-CorV vaccine 9 months post two dose vaccination schedule in a cohort of 292 participants, revealed that in 78.08% participants Omicron got neutralized ( Yu et al, 2022 ).…”

Breakthrough infections after COVID-19 vaccination: Insights, perspectives and challenges

“…The UK Health Security Agency (UKHSA) reports as well as other studies have also confirmed the descending vaccine effectiveness [ 42 , 43 ]. While further studies are needed, results from laboratory studies have suggested that the immunity resulting from a combination of vaccination and prior infection (hybrid immunity) or combined vaccination with different vaccine types (heterologous immunity) may offer some protection against the variant, which may be superior to vaccination with a single platform alone [ 44 , 45 ]. The Omicron variant, characterized by great immune evasion, escapes the majority of existing SARS-CoV-2 neutralizing antibodies [ 46 ].…”

Effect of Different Adjuvants on Immune Responses Elicited by Protein-Based Subunit Vaccines against SARS-CoV-2 and Its Delta Variant

“…By 18 January 2022, a total of 9,571,502,663 vaccine doses had been administered [ 6 ]. However, scientific consensus is growing that current vaccines show relatively low neutralizing immunogenicity, no broad-spectrum efficacy, and little lasting protective immunity [ 8 ]. To address this grim outlook, the development of more effective, long-lasting and broad-spectrum vaccines is essential.…”