Researchers from UK and Taiwan Develop New COVID-19 Vaccine RBD-SpyVLP Using Virus-Like Particle With Promising Results In Animal Studies
researchers from UK and Taiwan have demonstrated the potential of a new candidate vaccine called RBD-SpyVLP against the SARS-CoV-2 coronavirus in animal models.
In vivo trials involving animal models such as mice and pigs, low doses of the vaccine triggered a potent neutralizing antibody response that was stronger than the response induced by serum taken from patients who had recovered from COVID-19.
The research findings were published on a preprint server and are pending peer review.https://www.biorxiv.org/content/10.1101/2020.08.31.275701v1
The new virus-like particle (VLP) vaccine displays the receptor-binding domain (RBD) of the viral “spike” protein the surface structure that SARS-CoV-2 uses to bind to and access host cells.
Dr Alain Townsend from the University of Oxford and his other colleagues, utilized a technology called SpyTag/SpyCatcher to assemble the RBD of SARS-CoV-2 onto a VLP or virus-like particle.
The research team says the potent and polyclonal antibody response the vaccine-induced highlights its potential as an effective and affordable solution to addressing the current clinical and logistic challenges faced in the fight against COVID-19.
As of to date, no effective vaccines are available, although about 25 are undergoing clinical testing, and around 140 are in the preclinical stages of evaluation. These vaccine candidates are based on the viral vector, viral protein subunits, viral DNA and RNA, and VLPs, with most of them focused on the immunogenic potential of the SAR-CoV-2 spike protein.
The SARS-CoV-2 coronavirus binds the human angiotensin-converting enzyme 2 (ACE2) receptor using the RBD of the Spike S1 subunit, which enables the virus to enter host cells.
Dr Townsend told Thailand Medical News, “Of the many vaccine platforms, protein subunit vaccines generally have good safety profiles, and their production is rapid and easily scalable.”
The study team says numerous studies have recently demonstrated that the RBD of the SARS-CoV-2 spike protein triggers the production of neutralizing antibodies. Some studies have also shown that most of the potent neutralizing antibodies isolated from SARS-CoV-2- infected patients bind to the RBD.
Dr Townsend added, “We, therefore, chose to study the immunogenicity of RBD.”
In order to improve immunogenicity, the study team used SpyTag/SpyCatcher technology to conjugate SARS-CoV-2 RBD onto a VLP called mi3.
The unique utilization of VLPs to display protein antigens has previously been shown to increase immunogenicity by enabling drainage to lymph nodes and enhancing uptake by antigen-presenting cells.
By utilizing a panel of monoclonal antibodies isolated from convalescent patients, the researchers showed that all of the epitopes that could potentially trigger the generation of protective RBD-specific antibodies are present in RBD-SpyVLP.
Dr Townsend further added, “Since RBD-SpyVLPs induce antibody responses that tar
get multiple epitopes on the RBD, the chance of selecting neutralization-escape mutants should be greatly reduced. Circulating SARS-CoV-2 stains are constantly mutating, and the likelihood of persistence of the virus in the human population is high.”
Significantly in the study, only negligible antibody responses were seen when mice were vaccinated with 0.1 µg or 0.5 µg doses of RBD alone, but strong responses were seen once the RBD was displayed on the VLP.
Also serum from mice that received either 0.1 µg or 0.5 µg doses of RBD-SpyVLP exhibited high levels of antibody against the RBD of SARS-CoV-2, as well as the full-length spike protein and showed potent ACE2 blocking activity.
Dr Townsend commented, “All of these responses were higher than the levels found in plasma from convalescent humans. These results confirm the enhanced immunogenicity of RBD when displayed on SpyVLPs.”
Interestingly, RBD-SpyVLP vaccination also induced high titers of neutralizing antibodies in pigs using a dose that the authors intended to test in human trials (5 µg).
The study team reports that at a dose of 5 µg, similar neutralization titers were observed as when 100 µg of spike protein was administered.
The team says the finding that the RBD-SpyVLP vaccine candidate is highly immunogenic in mice and pigs suggests that it could potentially elicit protective antibody responses against SARS-CoV-2 in humans.
In addition, when the researchers tested the resilience of RBD-SpyVLP, they found it was stable at ambient temperature, resistant to freeze-thaw, and could be lyophilized (freeze-dried) and reconstituted, without any significant loss in activity or immunogenicity.
Dr Townsend added, “This resilience may not only simplify vaccine distribution worldwide, especially to countries where cold-chain ie low-temperature storage resources are incomplete but also reduce the overall vaccine cost by removing cold chain dependence.”
The study team concludes that overall, the research findings show that the RBD-SpyVLP is a potent and adaptable vaccine candidate that could potentially help to address the clinical and logistic challenges faced in combating the COVID-19 pandemic.
Dr Townsend said, “We are currently investigating cheaper and more scalable alternatives to produce RBD-SpyVLP to cope with the global demand for a SARS-CoV-2 vaccine.”
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