Abstract
The impact of the COVID-19 pandemic has been reduced since the application of vaccination programs, mostly shown in the reduction of hospitalized patients. However, the emerging variants, in particular Omicron, have caused a steep increase in the number of infections; this increase is, nevertheless, not matched by an increase in hospitalization. Therefore, a vaccine that induces cross-reactive antibodies against most or all variants is a potential solution for the issue of emerging new variants. Here, we present a vaccine candidate which displays receptor-binding domain (RBD) of SARS-CoV-2 on virus-like particles (VLP) that, in mice, not only induce strong antibody responses against RBD but also bind RBDs from other variants of concern (VOCs). The antibodies induced by wild-type (wt) RBD displayed on immunologically optimized Cucumber mosaic virus incorporated tetanus toxin (CuMVTT) VLPs bind to wt as well as RBDs of VOCs with high avidities, indicating induction of strongly cross-reactive IgG antibodies. Interestingly, similar cross-reactive IgA antibodies were induced in immunized mice. Furthermore, these cross-reactive antibodies demonstrated efficacy in neutralizing wt (Wuhan) as well as SARS-CoV-2 VOCs (Beta, Delta, and Gamma). In summary, RBDs displayed on VLPs are capable of inducing protective cross-reactive IgG and IgA antibodies in mice, indicating that it may be possible to cover emerging VOCs with a single vaccine based on wt RBD.
Highlights
The COVID-19 pandemic recently has been more dominated by variants of concern (VOCs) that have emerged in different countries around the globe [1–5]
We chemically coupled RBDwt protein expressed in eukaryotic HEK293 cells to Cucumber mosaic virus incorporated tetanus toxin (CuMVTT) virus-like particles (VLP)
Efficient conjugation was confirmed by SDS-PAGE analysis, where a single VLP subunit can be distinguished from subunits coupled to RBDwt
Summary
The COVID-19 pandemic recently has been more dominated by variants of concern (VOCs) that have emerged in different countries around the globe [1–5]. Mutations in the RBDs of these VOCs have been characterized in detail, and it was found that some mutations (e.g., E484K present in B.1.351 and P.1 variants) reduce recognition by antibodies induced by the wt SARS-CoV-2 strain [6–8], while other mutations (N501Y in B.1.1.7, B.1.351 and P.1 variants or L452R and E484Q in B.1.617.1 variant) primarily enhance affinity for the ACE2 receptor (Table 1) [9,10] likely being responsible for the enhanced infectivity of the latter strains. Both types of mutations cause reduced neutralization of VOCs by wt SARS-CoV-2 induced convalescent sera, either due to reduced recognition of the RBD or impaired competition of RBD with its receptor ACE2 [9].
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