Development of a Vaccine against SARS-CoV-2 Based on the Receptor-Binding Domain Displayed on Virus-Like Particles

Zha, Lisha; Chang, Xinyue; Zhao, Hongxin; Mohsen, Mona O.; Hong, Lei; Zhou, Yuhang; Chen, H.; Liu, Xuelan; Zhang, Jie; Liu, Dong; Wu, Ke; Martina, Benedict; Wang, Junfeng; Vogel, Monique; Bachmann, Martin F.

doi:10.3390/vaccines9040395

Cited by 35 publications

(40 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our first attempt to generate a COVID‐19 vaccine using CuMV TT VLPs platform, utilized eukaryotically expressed recombinant RBD which was chemically coupled to the VLPs using Succinimidyl 6‐((beta‐maleimidopropionamido)hexanoate) SMPH cross‐linker 21 . This method resulted in a vaccine candidate that induced high levels of RBD‐specific antibodies which were able to strongly inhibit RBD binding to ACE2 and neutralize SARS‐CoV‐2/ABS/NL20 virus 22 .…”

Section: Resultsmentioning

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

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

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

View full text Add to dashboard Cite

show abstract

“…Preclinical studies have evaluated the protective efficacy of several RBD-specific monoclonals, as well as RBD as a protective immunogen. Investigators evaluating RBD as a vaccine candidate have delivered the antigen either as DNA 81 , mRNA 7,74,[82][83][84][85] , viral vector 86 , soluble monomer or dimer 6,22,[87][88][89][90][91][92][93] , a fusion protein nanoparticle 16,26,[94][95][96][97][98] , or as a virus-like particle (VLP) 91,[99][100][101][102] . Additional RBD-based vaccine candidates in clinical trials (Table 2)…”

Section: Preclinical Studies Support Rbd As a Potent Vaccine Antigenmentioning

confidence: 99%

“…Vaccine researchers around the world have demonstrated preclinical immunogenicity of multimeric RBD vaccine candidates utilizing a variety of presentation methods including the following: ferritin nanoparticles 94,96,98,108,109 , single-component protein nanoparticles 95 , two-component protein nanoparticles either self-assembling 26 or assembled via SpyTag/Catcher technology 91,99,110 , and VLPs 102,111 . Together, these studies support the assertion that RBD displayed on a particle and co-administered with a suitable adjuvant represents a viable vaccine strategy for SARS-CoV-2, including against VOC.…”

Section: Prototype Rbd-np Vaccinementioning

confidence: 99%

Scientific rationale for developing potent RBD-based vaccines targeting COVID-19

et al. 2021

View full text Add to dashboard Cite

Vaccination of the global population against COVID-19 is a great scientific, logistical, and moral challenge. Despite the rapid development and authorization of several full-length Spike (S) protein vaccines, the global demand outweighs the current supply and there is a need for safe, potent, high-volume, affordable vaccines that can fill this gap, especially in low- and middle-income countries. Whether SARS-CoV-2 S-protein receptor-binding domain (RBD)-based vaccines could fill this gap has been debated, especially with regards to its suitability to protect against emerging viral variants of concern. Given a predominance for elicitation of neutralizing antibodies (nAbs) that target RBD following natural infection or vaccination, a key biomarker of protection, there is merit for selection of RBD as a sole vaccine immunogen. With its high-yielding production and manufacturing potential, RBD-based vaccines offer an abundance of temperature-stable doses at an affordable cost. In addition, as the RBD preferentially focuses the immune response to potent and recently recognized cross-protective determinants, this domain may be central to the development of future pan-sarbecovirus vaccines. In this study, we review the data supporting the non-inferiority of RBD as a vaccine immunogen compared to full-length S-protein vaccines with respect to humoral and cellular immune responses against both the prototype pandemic SARS-CoV-2 isolate and emerging variants of concern.

show abstract

“…To generate a vaccine candidate that effectively protects against SARS-CoV-2 virus, we produced a double mosaic particle by genetically fusing into individual CuMV TT subunits the fusion peptide (AA 817-855) and RBM. This double mosaic particle represents a next generation version of the recently reported CuMV TT -RBD and CuMV TT -RBM vaccine candidates, which already demonstrated potent immunogenicity in vaccinated mice [37,38]. In contrast to these previously described VLP-based vaccines, the new CuMV TT -DF vaccine candidate targets the RBD-ACE2 interaction interface as well as epitope required for fusion of the virus with the endosomal membrane.…”

Section: Introductionmentioning

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Development of a Vaccine against SARS-CoV-2 Based on the Receptor-Binding Domain Displayed on Virus-Like Particles

Cited by 35 publications

References 42 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

Scientific rationale for developing potent RBD-based vaccines targeting COVID-19

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

Contact Info

Product

Resources

About