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,...

Full description

Bibliographic Details
Main Authors: Xinyue Chang, Xuelan Liu, Mona O. Mohsen, Andris Zeltins, Byron Martina, Monique Vogel, Martin F. Bachmann
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/10/2/307
_version_ 1827652293089034240
author Xinyue Chang
Xuelan Liu
Mona O. Mohsen
Andris Zeltins
Byron Martina
Monique Vogel
Martin F. Bachmann
author_facet Xinyue Chang
Xuelan Liu
Mona O. Mohsen
Andris Zeltins
Byron Martina
Monique Vogel
Martin F. Bachmann
author_sort Xinyue Chang
collection DOAJ
description 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 (CuMV<sub>TT</sub>) 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.
first_indexed 2024-03-09T20:53:28Z
format Article
id doaj.art-5483067d47d9444397e0047aba704bd0
institution Directory Open Access Journal
issn 2076-393X
language English
last_indexed 2024-03-09T20:53:28Z
publishDate 2022-02-01
publisher MDPI AG
record_format Article
series Vaccines
spelling doaj.art-5483067d47d9444397e0047aba704bd02023-11-23T22:26:55ZengMDPI AGVaccines2076-393X2022-02-0110230710.3390/vaccines10020307Induction of Broadly Cross-Reactive Antibodies by Displaying Receptor Binding Domains of SARS-CoV-2 on Virus-like ParticlesXinyue Chang0Xuelan Liu1Mona O. Mohsen2Andris Zeltins3Byron Martina4Monique Vogel5Martin F. Bachmann6Department of Rheumatology and Immunology, University Hospital Bern, 3010 Bern, SwitzerlandInternational Immunology Centre, Anhui Agricultural University, Hefei 230036, ChinaDepartment of Rheumatology and Immunology, University Hospital Bern, 3010 Bern, SwitzerlandLatvian Biomedical Research & Study Center, Ratsupites 1, LV1067 Riga, LatviaArtemis Bio-Support, 2629 Delft, The NetherlandsDepartment of Rheumatology and Immunology, University Hospital Bern, 3010 Bern, SwitzerlandDepartment of Rheumatology and Immunology, University Hospital Bern, 3010 Bern, SwitzerlandThe 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 (CuMV<sub>TT</sub>) 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.https://www.mdpi.com/2076-393X/10/2/307COVID-19vaccinevirus-like particleCuMV<sub>TT</sub>
spellingShingle Xinyue Chang
Xuelan Liu
Mona O. Mohsen
Andris Zeltins
Byron Martina
Monique Vogel
Martin F. Bachmann
Induction of Broadly Cross-Reactive Antibodies by Displaying Receptor Binding Domains of SARS-CoV-2 on Virus-like Particles
Vaccines
COVID-19
vaccine
virus-like particle
CuMV<sub>TT</sub>
title Induction of Broadly Cross-Reactive Antibodies by Displaying Receptor Binding Domains of SARS-CoV-2 on Virus-like Particles
title_full Induction of Broadly Cross-Reactive Antibodies by Displaying Receptor Binding Domains of SARS-CoV-2 on Virus-like Particles
title_fullStr Induction of Broadly Cross-Reactive Antibodies by Displaying Receptor Binding Domains of SARS-CoV-2 on Virus-like Particles
title_full_unstemmed Induction of Broadly Cross-Reactive Antibodies by Displaying Receptor Binding Domains of SARS-CoV-2 on Virus-like Particles
title_short Induction of Broadly Cross-Reactive Antibodies by Displaying Receptor Binding Domains of SARS-CoV-2 on Virus-like Particles
title_sort induction of broadly cross reactive antibodies by displaying receptor binding domains of sars cov 2 on virus like particles
topic COVID-19
vaccine
virus-like particle
CuMV<sub>TT</sub>
url https://www.mdpi.com/2076-393X/10/2/307
work_keys_str_mv AT xinyuechang inductionofbroadlycrossreactiveantibodiesbydisplayingreceptorbindingdomainsofsarscov2onviruslikeparticles
AT xuelanliu inductionofbroadlycrossreactiveantibodiesbydisplayingreceptorbindingdomainsofsarscov2onviruslikeparticles
AT monaomohsen inductionofbroadlycrossreactiveantibodiesbydisplayingreceptorbindingdomainsofsarscov2onviruslikeparticles
AT andriszeltins inductionofbroadlycrossreactiveantibodiesbydisplayingreceptorbindingdomainsofsarscov2onviruslikeparticles
AT byronmartina inductionofbroadlycrossreactiveantibodiesbydisplayingreceptorbindingdomainsofsarscov2onviruslikeparticles
AT moniquevogel inductionofbroadlycrossreactiveantibodiesbydisplayingreceptorbindingdomainsofsarscov2onviruslikeparticles
AT martinfbachmann inductionofbroadlycrossreactiveantibodiesbydisplayingreceptorbindingdomainsofsarscov2onviruslikeparticles