Induction of Broadly Cross-Reactive Antibodies by Displaying Receptor Binding Domains of SARS-CoV-2 on Virus-like Particles

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.

RBD-mRNA vaccine induces broadly neutralizing antibodies against Omicron and multiple other variants and protects mice from SARS-CoV-2 challenge

“… 47 Similarly, a RBD displayed on Cucumber mosaic virus incorporated tetanus toxin (CuMV TT ) VLPs elicited neutralizing antibodies in mice against SARS-CoV-2 B.1.351, P.1, and B.1.617.2 variants. 48 In addition, a lumazine synthase VLP vaccine displaying SARS-CoV-2 RBD induced potent neutralizing antibodies against SARS-CoV-2 B.1.1.7, B.1.351, and P.1 variants, protecting immunized mice from SARS-CoV-2 challenge, with reduced clinical signs and pathological changes in the lung. 29 Moreover, a yeast cell-expressed Kappa (B.1.617.1)-RBD elicited neutralizing antibodies in mice against SARS-CoV-2 B.1.351, B.1.617.2, and B.1.1.529 variants.…”

“… 49 Overall, the neutralizing antibody titers induced by RBD vaccines are generally lower against these SARS-CoV-2 variants than against the prototypic virus strain. 29 , 47 , 48 , 49 …”

Vaccination using mutated receptor binding domains of SARS-CoV-2: Evidence for partial immune escape but not serotype formation

“…We have demonstrated previously that the VLP vaccine CuMV TT -RBD wt is highly immunogenic and induces high IgG titers against RBD wt and RBD of VOCs, able to neutralize wt Wuhan strain and VOCs (23,24). Using the same strategy, we generated CuMV TT -based variant vaccines, including RBDs with mutations that have been described to alter antibody recognition.…”

“…The RBDs of wt and VOCs (RBD 417 , RBD 484 , RBD 501 , and RBD trip ) were produced as described previously (23). Briefly, plasmids containing the RBD-encoding genes were transfected into Expi293F cells using ExpiFectamine 293 transfection kit (Gibco, Thermo Fisher Scientific, Waltham, MA, USA) according to the manufacturer's instruction.…”

Respiratory Viruses and Virus-like Particle Vaccine Development: How Far Have We Advanced?

“…To address the problems posed by the VOCs, the same research group also tested whether these VLP vaccines could be effective against multiple emerging variants of SARS-CoV-2. The wild-type RBD expressed on these VLPs were capable of interacting with the Beta, Gamma, and Delta VOCs with high avidities [ 137 ].…”