Future coronavirus vaccines may harness nanoparticles

• A nanoparticle-based COVID-19 vaccine may be cheap, safe, and effective.
• Preclinical study suggests that a single dose of a nanoparticle-based vaccine could provide robust immunity.
• It may be easier to store and transport than currently available vaccines.

To bring the COVID-19 pandemic under control will depend not only on safe and effective vaccines but also on the deployment of billions of relatively cheap doses.

While vaccines based on mRNA, such as those developed by Pfizer and Moderna, are highly effective and quick to develop, they are expensive to make and must be stored at very low temperatures.

For the Pfizer vaccine, this entails storage in a special freezer at a temperature between –80 and –60°C (-112 and -76°F).

Pfizer and Moderna also recommend that their respective vaccines are injected in two doses several weeks apart to maximize their efficacy.

These factors present challenges for low and middle income countries.

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Conventional vaccines that are based on inactivated, weakened, or genetically modified viruses can be highly effective and are easier to store and transport.

However, they take a long time to develop and are more likely to cause side effects.

Biochemists at Stanford University, CA, have created a prototype of a nanoparticle-based COVID-19 vaccine that they believe would not only be cheap, safe, and effective but also remain stable at room temperature.

They are even hopeful that their vaccine could be shipped and stored as a freeze-dried powder.

The scientists recently published the results of a preclinical study of the nanoparticle vaccine in the journal ACS Central Science.

“Our goal is to make a single-shot vaccine that does not require a cold-chain for storage or transport,” says senior author Dr. Peter S. Kim, Virginia and D. K. Ludwig Professor of Biochemistry at Stanford. “The target population for our vaccine is low and middle income countries.”

Iron-containing protein

The Stanford vaccine candidate is based on nanoparticles of an iron-containing protein called ferritin. Each ferritin nanoparticle is studded with several of the spike proteins that the virus uses to penetrate its host cells.

Before the pandemic, Dr. Kim’s lab had been developing a ferritin-based vaccine against the Ebola virus.

Previous research suggests that vaccinating laboratory animals with nanoparticles decorated with viral proteins — which effectively mimic whole viruses — elicits a stronger immune response than injecting them with the isolated viral proteins.

When the pandemic struck, the biochemists rapidly adapted this approach to target SARS-CoV-2, the virus that causes COVID-19.

First, they formulated a shortened version of the virus’ spike that is easier to synthesize and use. They bonded these shortened spikes to nanoparticles of ferritin, then used electron microscopy to confirm that they had the correct structure.

In mice, they compared the performance of this nanoparticle vaccine against four other vaccines:

• nanoparticles studded with full-length spikes
• full-length spikes alone
• shortened spikes alone
• the part of the spike that binds to host cells, known as the receptor binding domain

Neutralizing antibodies

A single dose of either nanoparticle vaccine provoked the animals’ immune system to produce “neutralizing” antibodies. These are the most effective type of antibodies because they block the virus from entering its host cells.

After a single dose, levels of these antibodies were roughly twice as high as the average levels found in the blood of patients who had recently recovered from COVID-19.

The same dose of the other vaccines, however, elicited little or no neutralizing antibodies in the mice.

All the vaccines elicited neutralizing antibodies after a second dose, but the nanoparticles with shortened spikes performed better than all the other vaccines, after either one or two doses.

The researchers caution that their nanoparticle-based COVID-19 vaccine is still a work in progress, however.

“This is really early stage, and there is still lots of work to be done,” says Abigail Powell, a former postdoctoral student in Dr. Kim’s lab and lead author of the paper. “But we think it is a solid starting point for what could be a single-dose vaccine regimen that does not rely on using a virus to generate protective antibodies following vaccination.”

The scientists are fine-tuning their vaccine candidate with a view to starting clinical trials in humans.

Crucially, they have showed that in an emergency, it is possible to develop a nanoparticle-based vaccine against a novel pathogen extremely quickly.

“It normally takes a decade to make a vaccine, if you are even successful,” says Dr. Kim. “This is unprecedented.”

Powell estimates that it took only 4 weeks from inception to the first tests in mice.

“Everybody had a lot of time and energy to devote to the same scientific problem,” she says. “It is a very unique scenario. I do not really expect I will ever encounter that in my career again.”

Universal coronavirus vaccine

The researchers recognize that their COVID-19 vaccine may not be needed now that several other effective vaccines have been approved or are close to completing clinical trials.

If so, they say their next challenge will be to develop a “universal” coronavirus vaccine, based on nanoparticles displaying proteins from several deadly coronaviruses.

These viruses would include SARS-CoV-1, which causes SARS; MERS; SARS-CoV-2; and possibly other coronaviruses with the potential to cause the next pandemic.

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