There are currently hundreds of COVID-19 vaccine candidates in development around the world. Some of the challenges facing them are the requirement of large doses, complex manufacturing, and cold-chain shipping and storage. An ultrapotent vaccine that is safe, effective at low doses, simple to produce, and stable outside of a freezer could enable vaccination against COVID-19 on a global scale. Now, a team of scientists at the University of Washington School of Medicine (UW Medicine) in Seattle report data on an innovative nanoparticle vaccine candidate that produces virus-neutralizing antibodies in mice at levels ten-times greater than is seen in people who have recovered from COVID-19 infections. The vaccine candidate has been transferred to two companies for clinical development.

This work is published in Cell in the paper titled, “Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2.”

Production schematic shows how coronavirus proteins are added to a computer-designed nanoparticle platform to create a candidate vaccine against COVID-19. The vaccine candidate was designed and tested in animal models by researchers at the University of Washington School of Medicine [Ian Haydon/UW Medicine Institute for Protein Design]
The vaccine candidate was developed using structure-based vaccine design techniques invented at UW Medicine. It is a self-assembling protein nanoparticle that displays 60 copies of the SARS-CoV-2 Spike protein’s receptor-binding domain in a highly immunogenic array. The molecular structure of the vaccine roughly mimics that of a virus, which may account for its enhanced ability to provoke an immune response.

Compared to vaccination with the soluble SARS-CoV-2 Spike protein, which is what many leading COVID-19 vaccine candidates are based on, the new nanoparticle vaccine produced ten times more neutralizing antibodies in mice, even at a six-fold lower vaccine dose.

The data also show a strong B-cell response after immunization, which can be critical for immune memory and a durable vaccine effect. When administered to a single nonhuman primate, the nanoparticle vaccine produced neutralizing antibodies targeting multiple different sites on the Spike protein. Researchers say this may ensure protection against mutated strains of the virus, should they arise.

The authors wrote that, “Antibodies elicited by the RBD-nanoparticles target multiple distinct epitopes, suggesting they may not be easily susceptible to escape mutations, and exhibit a lower binding:neutralizing ratio than convalescent human sera, which may minimize the risk of vaccine-associated enhanced respiratory disease.”

The lead authors of this paper are Alexandra Walls, PhD, a senior scientist in the laboratory of David Veesler, PhD, associate professor of biochemistry, and Brooke Fiala, a research scientist in the laboratory of Neil King, PhD, assistant professor at the Institute for Protein Design at UW Medicine.

“We hope that our nanoparticle platform may help fight this pandemic that is causing so much damage to our world,” said King. “The potency, stability, and manufacturability of this vaccine candidate differentiate it from many others under investigation.”

The high yield and stability of the assembled nanoparticles suggest that manufacture of the nanoparticle vaccines will be highly scalable. These results highlight the utility of robust antigen display platforms and have launched cGMP manufacturing efforts to advance the SARS-CoV-2-RBD nanoparticle vaccine into the clinic.

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