Nanoparticle vaccine against various coronaviruses

Colorized scanning electron micrograph of cells infected with SARS-CoV-2 virus particles (yellow), isolated from a patient sample. The tentacle-like protrusions from the cells are filapodia, which extend from infected cells and attach to neighboring cells, helping the virus to spread.NIAID Integrated Research Facility, Fort Detrick, Maryland

Coronaviruses have caused three major epidemics in the past 20 years—SARS, MERS, and the current COVID-19 pandemic. All three viruses belong to a group called betacoronaviruses (betaCoVs).

These viruses began as animal coronaviruses that jumped to human hosts. A vaccine that protects against a range of betaCoVs could prevent future outbreaks as well as help contain the current pandemic. A team of researchers led by Drs. Kevin Saunders and Barton Haynes at Duke University School of Medicine attempted to create such a vaccine. NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and National Cancer Institute (NCI) supported the work. It was described in Nature on May 10, 2021.

SARS-CoV-2 attaches to cells using a protein on its surface called the spike protein. Current SARS-CoV-2 vaccines cause cells in the body to make a version of this protein that elicits an immune response.

For the new vaccine, the researchers attached a part of this spike protein, called the receptor binding domain (RBD), to a protein designed to form nanometer-sized protein particles, or nanoparticles. Previous research has shown that antibodies to the RBD can neutralize many coronaviruses. Each of the self-assembling protein nanoparticles displays 24 copies of the RBD on its surface for the immune system to react to. Recent studies have found that putting multiple copies of the RBD on nanoparticles enhances the immune response. The team also added a compound to the vaccine called an adjuvant that is designed to further boost the immune response.

The researchers immunized monkeys with the vaccine. For comparison, they also tested mRNA vaccines similar to the approved Pfizer and Moderna vaccines. Monkeys immunized with either vaccine had antibodies in their serum that neutralized SARS-CoV-2. Their sera also neutralized virus variants of concern that originated in the United Kingdom, South Africa, and Brazil. In addition, they neutralized SARS-CoV-1, which causes SARS, and two related bat coronaviruses. Compared to the mRNA vaccine, the nanoparticle vaccine induced higher levels of neutralizing antibodies to these other betaCoVs.

The researchers then tested whether the vaccine protected monkeys from SARS-CoV-2. Vaccinated monkeys exposed to SARS-CoV-2 had no virus in their lower respiratory tracts two days after exposure. Only one monkey had detectable virus in nasal swabs, but this was gone after another two days.

These results suggest that, with further development, a nanoparticle vaccine could prevent future epidemics from a wide range of betaCoVs.

“This work represents a platform that could prevent, rapidly temper, or extinguish a pandemic,” Haynes says.

The results from the comparison mRNA vaccine are also reassuring. They suggest that vaccines already in use may provide some protection against coronaviruses other than SARS-CoV-2.

—by Brian Doctrow, Ph.D.