COVID-19 Nanoparticle Vaccine Give Rise to High Levels of Neutralizing Antibodies

Significance 

There are currently couple of 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. Conventional vaccines based on live-attenuated pathogens present a risk of reversion to pathogenic virulence while inactivated pathogen vaccines often lead to a weak immune response. Subunit vaccines were developed to overcome these issues. However, these vaccines may suffer from a limited immunogenicity and, in most cases, the protection induced is only partial. A new generation of vaccines based on nanoparticles has shown great potential to address most of the limitations of conventional and subunit vaccines. This is due to recent advances in chemical and biological engineering, which allow the design of nanoparticles with a precise control over the size, shape, functionality and surface properties, leading to enhanced antigen presentation and strong immunogenicity. Now, a team of scientists at the University of Washington School of Medicine   designed 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.

The authors designed and tested the vaccine candidate in animal models. They developed it 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.

Their findings 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.

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 authors hope that our nanoparticle platform may help fight this pandemic that is causing so much damage to our world. 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. Indeed the current COVID-19 pandemic proved that nanomedicine is crucial to delivering effective innovative vaccines

COVID-19 Nanoparticle Vaccine Elicits High Levels of Protective Antibodies in Mice - Medicine Innovates

About the author

Neil King, PhD, Assistant Professor

Assistant Professor
Institute for Protein Design
University of Washington
NanoES
Seattle, WA 98195-7370

Neil joined the Institute for Protein Design as a Translational Investigator in early 2014. During his postdoc, he pioneered the development of general computational methods for designing self-assembling proteins with atomic-level accuracy. His group at the IPD is using and extending these methods to design functional protein nanomaterials for applications in targeted drug delivery and the design of next-generation vaccines.

Proteins are Nature’s building block of choice for the construction of ‘molecular machines’: stable yet dynamic assemblies with unparalleled abilities in molecular recognition, catalysis, and responsiveness to changes in environment. Neil’s group is incorporating these features into the design of functional nanomaterials with the goal of creating new opportunities for the treatment of disease. Working with collaborators around the world, they are establishing a design-build-test cycle to use feedback from functional assays in vitro and in vivo to optimize the performance of the designed materials.

Reference

Alexandra C. Walls, Brooke Fiala,  et al.  Neil P. King. Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2. Cell, Volume 183, Issue 5,  2020, Pages 1367-1382.e17

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