COVID-19 vaccine with IPD nanoparticles seeks full approval

The vaccine, now called SKYCovione, is a tiny ball of protein studded with 60 copies of the SARS-CoV-2 receptor-binding domain (shown in red). Image: Ian C Haydon / UW Medicine Institute for Protein Design

A COVID-19 vaccine developed at the University of Washington School of Medicine has proven safe and effective in late-stage clinical testing. SK bioscience, the company leading the vaccine’s clinical development abroad, is seeking full approval for its use in South Korea and beyond.

If approved by regulators, the vaccine will be made available through COVAX, an international effort to equitably distribute COVID vaccines around the world. In addition, the Korean government has agreed to purchase 10 million doses for domestic use.

The Seattle scientists behind the new vaccine sought to create a ‘second-generation’ COVID-19 vaccine that is safe, effective at low doses, simple to manufacture, and stable without deep freezing. These attributes would enable vaccination at a global scale by reaching people in areas where medical, transportation, and storage resources are limited.

“We know we have more than two billion people worldwide that have not received a single dose of vaccine,” said David Veesler, associate professor of biochemistry at UW School of Medicine and co-developer of the vaccine. “If our vaccine is distributed through COVAX, it will allow it to reach these people that need to have access to doses.”

The University of Washington is licensing the vaccine technology royalty-free for the duration of the pandemic.

From SK: SK bioscience and GSK’s Adjuvanted COVID-19 Vaccine Candidate Meets Coprimary Objectives in a Phase III Study; Biologics License Application Submitted for SKYCovione™(GBP510/GSK adjuvant) in South Korea

Clinical trial results

A multinational Phase 3 trial involving 4,037 adults over 18 years of age found that the vaccine, now called SKYCovione, elicits roughly three times more protective antibodies than the Oxford/AstraZeneca vaccine Vaxzevria. In these studies, SKYCovione or Vaxzevria was administered twice with an interval of four weeks.

In addition, the ‘antibody conversion rate’, which refers to the proportion of subjects whose neutralizing antibody level increased fourfold or more after vaccination, was higher with SKYCovione. Ninety-eight percent of subjects achieved antibody conversion, compared to 87 percent for the control vaccine.

Among study participants 65 years of age or older, the antibody conversion rate of those vaccinated with SKYCovione was over 95 percent, which was a significant difference compared to the control vaccine (about 79 percent for the elderly), raising the expectation that SKYCovione can be used effectively to protect the elderly.

The Phase 3 trial also found that T cell activation levels, which help protect the body from COVID-19, were similar or higher with SKYCovione.

Phase 1/2 trial results announced by SK bioscience last November and posted as a preprint last month found that SKYCovione was safe and produced virus-neutralizing antibodies in all trial participants receiving the adjuvanted vaccine. In the Phase 3 trial, there were again no serious adverse reactions to the vaccine.

How the vaccine works

Unlike the earliest approved vaccines for COVID-19 that make use of mRNA, viral vectors, or an inactivated virus, SKYCovione is made of proteins that form tiny particles studded with fragments of the pandemic coronavirus. These nanoparticles were designed by scientists at UW Medicine and advanced into clinical trials by SK bioscience and GlaxoSmithKline with financial support from the Coalition for Epidemic Preparedness Innovations. SKYCovione includes GlaxoSmithKline’s pandemic adjuvant, AS03.

“This vaccine was designed at the molecular level to present the immune system with a key part of the coronavirus spike protein. We know this part, called the receptor-binding domain, is targeted by the most potent antibodies,” said Neil King, an assistant professor of biochemistry at UW Medicine and co-developer of the vaccine.

Two laboratories in the UW Medicine Department of Biochemistry led the initial development of the protein-based vaccine: the King Lab pioneered the vaccine’s self-assembling protein nanoparticle technology while the Veesler Lab identified and integrated a key fragment of the SARS-CoV-2 Spike protein onto the nanoparticles.

Years in the making

David Veesler, an assistant professor and HHMI investigator at UW Medicine, has been studying coronaviruses since 2015. Using advanced electron microscopes, researchers in the Vessler lab were the first to identify how the novel coronavirus enters human cells. They were also among the first to report, in Cell, detailed structural information about the virus’ spike protein, a critical piece of its infectious machinery.

In 2016, scientists in the King lab at the UW Medicine Institute for Protein Design began developing a strategy for building a new type of vaccine. They designed proteins that self-assemble into precise spherical particles and later showed that these nanoparticles could be decorated with proteins from a virus. 

Researchers from the two labs worked together in the earliest months of the COVID-19 pandemic to design a protein nanoparticle decorated with 60 copies of the Spike protein receptor-binding domain. The designed nanostructure mimics the repetitive nature of proteins on the surface of viruses, a property that the immune system responds strongly to.

“In order to focus the antibody response where it matters most, we decided to include in the vaccine only a key fragment of the coronavirus spike protein, known as the receptor-binding domain,” said Veesler. “We are thrilled to see that this strategy paid off and has led to a successful subunit vaccine.”

In initial animal studies reported in late 2020 in Cell, the nanoparticle vaccine was found to produce high levels of virus-neutralizing antibodies at low doses. These antibodies target several different sites on the coronavirus Spike protein, a desirable quality that may enhance protection against future coronavirus variants. 

Further preclinical studies, published in Nature, also showed that the vaccine conferred robust protection and produced a strong B-cell response in non-human primates, which may improve how long the protective effects of the vaccine last.

In a recent preprint, a third dose of the vaccine was found to confer strong protection against the Omicon variant of COVID-19 in animals. SK bioscience will initiate testing third doses in 750 human adults soon.

The role of philanthropy

Development of the vaccine at UW Medicine was supported by the Bill & Melinda Gates Foundation, National Institutes of Health, Pew Charitable Trust, Burroughs Wellcome Fund, Fast Grants, and by gifts from The Audacious Project, Jodi Green and Mike Halperin, Nicolas and Leslie Hanauer, Rob Granieri, anonymous donors, and other granting agencies, including Open Philanthropy.

SK bioscience received support for clinical testing from the Bill & Melinda Gates Foundation and the Center for Epidemic Preparedness (CEPI), which is a global partnership supporting vaccine development to fight pandemics. CEPI, along with the World Health Organization and Gavi, the Vaccine Alliance, are co-leaders of COVAX.