AP205 VLPs Based on Dimerized Capsid Proteins Accommodate RBM Domain of SARS-CoV-2 and Serve as an Attractive Vaccine Candidate

Liu, Xuelan; Chang, Xinyue; Rothen, Dominik A.; Derveni, Mariliza; Krenger, Pascal S.; Roongta, Salony; Wright, Edward; Vogel, Monique; Tars, K.; Mohsen, Mona O.; Bachmann, Martin F.

doi:10.3390/vaccines9040403

Cited by 36 publications

(36 citation statements)

References 48 publications

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“…The developed vaccine‐induced antibodies that completely neutralized MERS‐CoV/EMC/2012 isolate 46 . Furthermore, we have shown that fusing RBM into AP205‐VLPs results in an effective vaccine candidate which induced RBD‐ and spike‐specific antibodies which were capable of neutralizing the wild‐type virus SARS‐CoV‐2/ABS/NL20 35 . Development of AP205‐RBM vaccine required a refolding process which typically results in lower amounts of correctly folded target protein and may be distinguished from re‐assembly processes used for HPV and hepatitis E virus (HEV) vaccines 36 .…”

Section: Discussionmentioning

confidence: 99%

A scalable and highly immunogenic virus‐like particle‐based vaccine against SARS‐CoV‐2

Mohsen

Baļķe

Zinkhan

et al. 2021

Allergy

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Background SARS‐CoV‐2 caused one of the most devastating pandemics in the recent history of mankind. Due to various countermeasures, including lock‐downs, wearing masks, and increased hygiene, the virus has been controlled in some parts of the world. More recently, the availability of vaccines, based on RNA or adenoviruses, has greatly added to our ability to keep the virus at bay; again, however, in some parts of the world only. While available vaccines are effective, it would be desirable to also have more classical vaccines at hand for the future. Key feature of vaccines for long‐term control of SARS‐CoV‐2 would be inexpensive production at large scale, ability to make multiple booster injections, and long‐term stability at 4℃. Methods Here, we describe such a vaccine candidate, consisting of the SARS‐CoV‐2 receptor‐binding motif (RBM) grafted genetically onto the surface of the immunologically optimized cucumber mosaic virus, called CuMV TT ‐RBM. Results Using bacterial fermentation and continuous flow centrifugation for purification, the yield of the production process is estimated to be >2.5 million doses per 1000‐litre fermenter run. We demonstrate that the candidate vaccine is highly immunogenic in mice and rabbits and induces more high avidity antibodies compared to convalescent human sera. The induced antibodies are more cross‐reactive to mutant RBDs of variants of concern (VoC). Furthermore, antibody responses are neutralizing and long‐lived. In addition, the vaccine candidate was stable for at least 14 months at 4℃. Conclusion Thus, the here presented VLP‐based vaccine may be a good candidate for use as conventional vaccine in the long term.

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Section: Discussionmentioning

confidence: 99%

A scalable and highly immunogenic virus‐like particle‐based vaccine against SARS‐CoV‐2

Mohsen

Baļķe

Zinkhan

et al. 2021

Allergy

Self Cite

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“…Notably, the CuMV TT -RBM vaccine demonstrated as high an immunogenicity as CuMV TT -RBD, even several months post vaccination and induced high levels of neutralizing antibodies. In addition, another vaccine candidate based on AP205 VLPs C-terminally fused to RBM (AP205-RBM) demonstrated potent immunogenicity in mice and induced neutralizing antibodies [41].…”

Section: Discussionmentioning

confidence: 99%

A Novel Double Mosaic Virus-like Particle-Based Vaccine against SARS-CoV-2 Incorporates Both Receptor Binding Motif (RBM) and Fusion Domain

et al. 2021

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COVID-19 has emerged, and has rapidly become a major health problem worldwide, causing millions of mortalities. Vaccination against COVID-19 is the most efficient way to stop the pandemic. The goal of vaccines is to induce neutralizing antibodies against SARS-CoV-2 virus. Here, we present a novel double mosaic virus-like particle (VLP) displaying two independent neutralizing epitopes, namely the receptor binding motif (RBM) located in S1 and the fusion peptide (AA 817–855) located in S2. CuMVTT virus-like particles were used as VLP scaffold and both domains were genetically fused in the middle of CuMVTT subunits, which co-assembled into double mosaic particles (CuMVTT-DF). A single fusion mosaic particle (CuMVTT-FP) containing the fusion peptide only was used for comparison. The vaccines were produced in E. coli, and electron microscopy and dynamic light scattering confirmed their integrity and homogeneity. In addition, the CuMVTT-DF vaccine was well recognized by ACE2 receptor, indicating that the RBM was in native conformation. Both CuMVTT-FP and CuMVTT-DF vaccines induced high levels of high avidity IgG antibodies as well as IgA recognizing spike and RBD in the case of CuMVTT-DF. Both vaccine candidates induced virus-neutralizing antibodies indicating that the fusion peptide can independently induce virus-neutralizing antibodies. In contrast, CuMVTT-DF containing both RBM and fusion peptide induced a higher level of neutralizing antibodies suggesting that the new double mosaic vaccine candidate CuMVTT-DF consisting of two antigens in one VLP maybe an attractive candidate for scale-up in a bacterial fermentation process for clinical development.

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“…As shown recently, such spacing is sometimes not present in native viruses as e.g. SARS-CoV-2 ( 4 ), but can easily be achieved with recombinant VLPs ( 5 – 7 ).…”

Section: Introductionmentioning

confidence: 99%

TLR7 Signaling Shapes and Maintains Antibody Diversity Upon Virus-Like Particle Immunization

et al. 2022

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Virus-like particles (VLPs) are used in different marketed vaccines and are able to induce potent antibody responses. The innate pattern recognition receptors TLR7/8 recognize single stranded (ss) RNA naturally packaged into some VLPs and have been shown to enhance the production of IgG antibodies upon immunization. Here we demonstrate that, upon immunization with RNA-loaded bacteriophage-derived VLP Qβ, TLR7 signaling accelerates germinal center formation, promotes affinity/avidity maturation of VLP-specific IgG and isotype switching to IgG2b/2c. These findings extrapolated to antigens displayed on Qβ; as Fel d 1, the major cat allergen, chemically attached to Qβ also induced higher affinity/avidity IgG2b/2c antibodies in a TLR7-dependent fashion. Chimeric mice lacking TLR7-expression exclusively in B cells demonstrated that the enhanced IgG responses were driven by a B cell intrinsic mechanism. Importantly, deep sequencing of the BCR repertoire of antigen-specific B cells demonstrated higher diversity in mice with TLR7 signaling in B cells, suggesting that TLR7-signaling drives BCR repertoire development and diversity. Furthermore, the current data demonstrate that high levels of clonal diversity are reached early in the response and maintained by TLR7 signaling. In conclusion, TLR7 signaling enhances levels and quality of IgG antibodies, and this finding has major implications for vaccine design.

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AP205 VLPs Based on Dimerized Capsid Proteins Accommodate RBM Domain of SARS-CoV-2 and Serve as an Attractive Vaccine Candidate

Cited by 36 publications

References 48 publications

A scalable and highly immunogenic virus‐like particle‐based vaccine against SARS‐CoV‐2

A scalable and highly immunogenic virus‐like particle‐based vaccine against SARS‐CoV‐2

A Novel Double Mosaic Virus-like Particle-Based Vaccine against SARS-CoV-2 Incorporates Both Receptor Binding Motif (RBM) and Fusion Domain

TLR7 Signaling Shapes and Maintains Antibody Diversity Upon Virus-Like Particle Immunization

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