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Stanford nanoparticle COVID-19 vaccine shows early success in mice

Stanford University researchers have developed a nanoparticle vaccine that has shown in mouse studies to effectively build coronavirus immunities.

Stanford University researchers, led by biochemist Peter Kim, PhD, have begun developing a new vaccine candidate for COVID-19 that doesn't need to be kept cold for storage or shipping, and could immunize people against the virus in only one shot.

Whereas many vaccines build immunity by exposing people to weakened forms of a virus, this vaccine prompts an immune response by using the same feature of the SARS-CoV-2 virus that triggers immunity in the body: its protein spikes.

The researchers designed their own version of these spikes to attach to smaller-than-microscopic -- or "nano" -- particles of the iron-containing protein ferritin, developed from the bacteria Helicobacter pylori. By adding the spikes around this nanoparticle core, the researchers hope the nanoparticle vaccine will elicit that same -- or an even stronger -- immune response than the actual virus.

The Stanford-developed nanoparticle vaccine has been tested only in mice, but the results, published recently in ACS Central Science, showed promise.

"Our goal is to make a single-shot vaccine that does not require a cold-chain for storage or transport. If we're successful at doing it well, it should be cheap too," Kim said in an interview with the Stanford News Service. "The target population for our vaccine is low- and middle-income countries."

The Moderna and Pfizer COVID-19 vaccines in use in the United States require cold storage because their fragile genetic instructions must be delivered into the body, via mRNA, for making harmless spike proteins. Because the nanoparticle-based vaccine doesn't contain those fragile components, researchers in Kim's lab believe their vaccine could be stored and shipped at room temperature, which is one reason it's a relatively inexpensive option.

Creating SARS-CoV-2 spike proteins

In addition to being cheaper and less fragile than mRNA vaccines, a nanoparticle vaccine also has some advantages over vaccines that rely on weakened virus. By comparison, nanoparticle vaccines can be made more quickly and may lead to fewer side effects.

The researchers chose to work on a nanoparticle vaccine, in part, because these ferritin nanoparticles have been previously tested in humans; ferritin nanoparticles are even at the core of a universal influenza vaccine being tested in human clinical trials.

Because the spike protein from SARS-CoV-2 is large, scientists often formulate abridged versions that are simpler to make and easier to fuse to the nanoparticle. In creating their nanoparticle vaccine, the Kim lab researchers decided to remove a section of the spike near the bottom of a coronavirus cell, thinking it might improve their results.

Testing the nanoparticle vaccine candidates

To test the potential of their shortened-spike nanoparticle vaccine, they tried out four variations: nanoparticles with full spikes; full spikes without nanoparticles; partial spikes without nanoparticles; and a vaccine containing just the section of the spike that binds to cells during infection.

The researchers gauged the performance of these four potential vaccines by measuring levels of neutralizing antibodies in the mice after the animals received the vaccines. Neutralizing antibodies are blood proteins that defend against foreign objects in the body.

Overall, the nanoparticle vaccine with the shortened spike outperformed all of the alternative versions in the mouse experiments. After the first dose, both nanoparticle-based vaccines produced higher levels of neutralizing antibodies than the alternatives, and the levels were twice as high as what has been found in people who have had COVID-19.

Although one dose seemed to elicit a robust immune response, the researchers still checked the outcome of two doses. After a second dose, the mice that received the shortened-spike nanoparticle vaccine had the highest levels of neutralizing antibodies relative to all other versions.

What comes next

Researchers want to test their vaccines in people through clinical trials, and they are also interested in developing a freeze-dried, powder-form vaccine option to further simplify shipping and storage.

It's possible, Kim said, that their vaccine will not be needed for the current pandemic. But the team plans to continue the research, refocusing on a more universal version that could be effective against SARS-CoV-1, MERS, SARS-CoV-2 and future coronaviruses.

"Vaccines are one of the most profound achievements of biomedical research. They are an incredibly cost-effective way to protect people against disease and save lives," Kim said.

"This coronavirus vaccine is part of work we're already doing ... and I'm glad that we're in a situation where we could potentially bring something to bear if the world needs it," he added.

Image portrays a schematic visualization of the ferritin nanoparticle with shortened coronavirus spike proteins, which is the basis of a SARS-CoV-2 vaccine candidate from Stanford. Courtesy of Duo Xu.

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