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

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,...

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Veröffentlicht in:Vaccines (Basel) Jg. 10; H. 2; S. 307
Hauptverfasser: Chang, Xinyue, Liu, Xuelan, Mohsen, Mona O., Zeltins, Andris, Martina, Byron, Vogel, Monique, Bachmann, Martin F.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Switzerland MDPI AG 16.02.2022
MDPI
Schlagworte:
Antibodies
Binding
Coronaviruses
COVID-19
CuMVTT
Domains
E coli
Experiments
Immunization
Immunoglobulin A
Immunoglobulin G
Mutation
Pandemics
Plant virus diseases
Plasmids
Proteins
Receptors
Severe acute respiratory syndrome coronavirus 2
Statistical analysis
Tetanus
Tetanus toxin
Toxins
Vaccination
vaccine
Vaccines
Viral diseases
virus-like particle
Virus-like particles
Viruses
United States > US
Switzerland
COVID-19
CuMVTT
vaccine
virus-like particle
ISSN:2076-393X, 2076-393X
Online-Zugang:Volltext
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Zusammenfassung: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.
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These authors contributed equally to this work.
ISSN:2076-393X
2076-393X
DOI:10.3390/vaccines10020307