An enveloped virus-like particle vaccine expressing a stabilized prefusion form of the SARS-CoV-2 spike protein elicits highly potent immunity

Fluckiger, Anne-Catherine; Ontsouka, Barthelemy; Bozic, Jasminka; Diress, Abebaw; Ahmed, Tanvir; Berthoud, Tamara; Tran, Anh; Duque, Diane; Liao, Mingmin; McCluskie, Michael J.; Díaz‐Mitoma, Francisco; Anderson, David E.; Soare, Catalina

doi:10.1016/j.vaccine.2021.07.034

Cited by 29 publications

(43 citation statements)

References 41 publications

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“…Expression plasmid for the production of eVLPs expressing SARS-CoV-2 S proteins have been described previously (Fluckiger et al 2021). Briefly, the prefusion modified form of S was obtained by introducing a mutation at the furin cleavage site (RRAR → GSAS) and two Proline at position K986-V987 of the Wuhan reference and swapping the transmembrane cytoplasmic domain with that of the VSV-G protein.…”

Section: Plasmids Evlp Production and Adjuvant Formulationmentioning

confidence: 99%

“…VBI-2902a was produced using the Wuhan-Hu-1 spike sequence (Genbank accession number MN908947), and VBI-2905a was produced using the same strategy with S sequence from Beta variant B.1.351 isolate EPI_ISL_911433 (GISAID). Production and purification of eVLPs were conducted as described elsewhere (Fluckiger et al 2021). The preparation of eVLPs expressing either Wuhan reference Spike or Beta variant Spike were formulated in Aluminum phosphate (Alum, Adjuphos® , Invitrogen) to obtain vaccine candidate VBI-2902a and VBI-2905a, respectively.…”

Section: Plasmids Evlp Production and Adjuvant Formulationmentioning

confidence: 99%

“…Mice were maintained in a controlled environment in accordance with the "Guide for the Care and Use of Laboratory Animals" at the Animal Research facility of the NRC's Human Health Therapeutics Research Centre (Montreal). Mice were randomly assigned to experimental groups of 10 to 15 mice and received intraperitoneal (IP) injections with 0.5 mL of adjuvanted SARS-CoV-2 eVLPs as described elsewhere (Fluckiger, 2021). Blood was collected on day -1 before injection and day 14 after each injection for humoral immunity assessment at time of euthanasia.…”

Section: Mouse Immunization Studymentioning

confidence: 99%

“…VBI-2902a is an eVLP-based vaccine candidate that expresses a modified prefusion SARS-CoV-2 S protein from the ancestral Wu-1 strain, adjuvanted with Alum (Fluckiger et al, 2021). VBI-2905a expresses a modified prefusion SARS-CoV-2 S protein from the Beta variant and is also adjuvanted with Alum.…”

Section: Heterologous Boosting With Evlps Bearing S Protein From the Beta Variant Broadens Immunitymentioning

confidence: 99%

“…Recently, we developed a SARS-CoV-2 candidate vaccine, VBI-2902a, comprised of enveloped virus-like particles (eVLPs) expressing a modified prefusion form of the ancestral S sequence, adjuvanted with aluminum phosphate (Alum). We recently demonstrated that VBI-2902a induced strong neutralizing activity in mouse immunogenicity studies, and protected hamsters from SARS-CoV-2 challenge using a virus related to the ancestral isolate (Fluckiger et al 2021). Interim results from a Phase I clinical study in healthy, seronegative individuals (ClinicalTrials.gov Identifier: NCT04773665) demonstrated robust (4.3-fold greater) neutralizing activity 28 days after a second, 5µg dose of VBI-2902a, relative to a panel of COVID-19 convalescent sera.…”

Section: Introductionmentioning

confidence: 99%

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Use of eVLP-based vaccine candidates to broaden immunity against SARS-CoV-2 variants

Bozic¹,

Ahmed²,

Ontsouka³

et al. 2021

Preprint

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Rapid emergence of SARS-CoV-2 variants is a constant threat and a major hurdle to reach heard immunity. We produced VBI-2905a, an enveloped virus-like particules (eVLP)-based vaccine candidate expressing prefusion spike protein from the Beta variant that contains several escape mutation. VBI-2905a protected hamsters against infection with a Beta variant virus and induced high levels of neutralizing antibodies against Beta RBD. In a heterologous vaccination regimen, a single injection of VBI-2905a in animals previously immunized with VBI-2902, a vaccine candidate expressing S from ancestral SARS-CoV-2, hamsters were equally protected against Beta variant infection. As an alternate strategy to broaden immunity, we produced a trivalent vaccine expressing the prefusion spike protein from SARS-CoV-2 together with unmodifed S from SARS-CoV-1 and MERS-CoV. Relative to immunity induced against the ancestral strain, the trivalent vaccine VBI-2901a induced higher and more consistent antibody binding and neutralizing responses against a panel of variants including Beta, Delta, Kappa, and Lambda, with evidence for broadening of immunity rather than just boosting cross-reactivity antibodies.

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Section: Plasmids Evlp Production and Adjuvant Formulationmentioning

confidence: 99%

Section: Plasmids Evlp Production and Adjuvant Formulationmentioning

confidence: 99%

Section: Mouse Immunization Studymentioning

confidence: 99%

Section: Heterologous Boosting With Evlps Bearing S Protein From the Beta Variant Broadens Immunitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Use of eVLP-based vaccine candidates to broaden immunity against SARS-CoV-2 variants

Bozic¹,

Ahmed²,

Ontsouka³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

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Development of virus‐like particles‐based vaccines against coronaviruses

Yong

Liew

Ong

et al. 2022

Biotechnology Progress

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Severe acute respiratory syndrome coronavirus (SARS‐CoV), Middle East respiratory syndrome coronavirus (MERS‐CoV), and the current severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) are the most impactful coronaviruses in human history, especially the latter, which brings revolutionary changes to human vaccinology. Due to its high infectivity, the virus spreads rapidly throughout the world and was declared a pandemic in March 2020. A vaccine would normally take more than 10 years to be developed. As such, there is no vaccine available for SARS‐CoV and MERS‐CoV. Currently, 10 vaccines have been approved for emergency use by World Health Organization (WHO) against SARS‐CoV‐2. Virus‐like particle (VLP)s are nanoparticles resembling the native virus but devoid of the viral genome. Due to their self‐adjuvanting properties, VLPs have been explored extensively for vaccine development. However, none of the approved vaccines against SARS‐CoV‐2 was based on VLP and only 4% of the vaccine candidates in clinical trials were based on VLPs. In the current review, we focused on discussing the major advances in the development of VLP‐based vaccine candidates against the SARS‐CoV, MERS‐CoV, and SARS‐CoV‐2, including those in clinical and pre‐clinical studies, to give a comprehensive overview of the VLP‐based vaccines against the coronaviruses.

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Virus‐like particles as powerful vaccination strategy against human viruses

Hadj Hassine,

Ben M'hadheb,

Almalki

et al. 2023

Reviews in Medical Virology

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Nowadays, viruses are not only seen as causative agents of viral infectious diseases but also as valuable research materials for various biomedical purposes, including recombinant protein production. When expressed in living or cell‐free expression systems, viral structural proteins self‐assemble into virus‐like particles (VLPs). Mimicking the native form and size of viruses and lacking the genetic material, VLPs are safe and highly immunogenic and thus can be exploited to develop antiviral vaccines. Some vaccines based on VLPs against various infectious pathogens have already been licenced for human use and are available in the commercial market, the latest of which is a VLP‐based vaccine to protect against the novel Coronavirus. Despite the success and popularity of VLP subunit vaccines, many more VLPs are still in different stages of design, production, and approval. There are still many challenges that require to be addressed in the future before this surface display system can be widely used as an effective vaccine strategy in combating infectious diseases. In this review, we highlight the use of structural viral proteins to produce VLPs, emphasising their intrinsic properties, structural classification, and main expression host systems. We also compiled the recent scientific literature about VLP‐based vaccines to underline the recent advances in their application as a vaccine strategy for preventing and fighting virulent human pathogens. Finally, we presented the key challenges and possible solutions for VLP‐based vaccine production.

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An enveloped virus-like particle vaccine expressing a stabilized prefusion form of the SARS-CoV-2 spike protein elicits highly potent immunity

Cited by 29 publications

References 41 publications

Use of eVLP-based vaccine candidates to broaden immunity against SARS-CoV-2 variants

Use of eVLP-based vaccine candidates to broaden immunity against SARS-CoV-2 variants

Development of virus‐like particles‐based vaccines against coronaviruses

Virus‐like particles as powerful vaccination strategy against human viruses

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