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Stanford Scientists Are Creating Single-Dose Nanoparticle COVID-19 Vaccine

The new nanoparticle COVID-19 vaccine would only require one dose to immunize our bodies.

A team of researchers is developing a new type of COVID-19 vaccine — containing nanoparticles studded with the same proteins we see on the surface spikes of the virus, according to a new study published in the journal ACS Central Science.

While it's still in an early, pre-clinical phase, the new vaccine could be a less pricey alternative, and work with just one, single dose.

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Stanford scientists creating nanoparticle COVID-19 vaccine

The surface spikes are the reason why coronaviruses — where corona is Latin for "crown" — are so effective at infecting a host cell via fusion, which creates a passageway for viral genomes to enter and hijack human cells' machinery, and in turn reproduce more viruses.

Scientists say the coronavirus spikes may be used as antigens, which enables their presence inside the body to trigger an immune response, according to a blog post on Stanford University's website.

"Our goal is to make a single-shot vaccine that does not require a cold-chain for storage or transport," said Stanford Biochemist Peter S. Kim, who is also the D.K. Ludwig biochemistry professor. "If we're successful at doing it well, it should be cheap too. The target population for our vaccine is low- and middle-income countries."

Pfizer, Moderna's mRNA vaccines are more expensive, multiple doses needed

Nanoparticle vaccines are unique — balancing the effectiveness of viral-based vaccines with the simpler production and safety of subunit vaccines. Vaccines capable of delivering antigens with viruses are typically more effective than ones containing only isolated fragments of a virus. But the former can take more time to produce, often cause side effects, and need proper refrigeration.

Nucleic acid vaccines — like the mRNA vaccines from Pfizer and Moderna which have received emergency use authorization from the FDA — take even less time to produce than nanoparticle vaccines, but the downside is the expensive manufacturing process, in addition to the multiple-dose requirement.

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Nanoparticle COVID-19 vaccine aims for human clinical trials

Early tests in mice show the Stanford nanoparticle vaccine could achieve COVID-19 immunity with only one dose. The researchers are designing their vaccine for easy access, with shipping and storage moving forward in freeze-dried, powder form. Comparatively, vaccines in the U.S. closest to complete development all need cold storage temperatures — ranging from roughly 46 to -94 degrees Fahrenheit (8 to -70 degrees Celsius).

"This is really early stage and there is still lots of work to be done," said a former postdoctoral scholar of Kim's lab and lead author of the paper, Abigail Powell. "But we think it is a solid starting point for what could be a single-dose vaccine regimen that doesn't rely on using a virus to generate protective antibodies following vaccination."

The researchers' forthcoming vaccine candidate is still undergoing fine-tuning, with hopes of bringing it closer to human clinical trials.

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Imaging coronavirus spikes, molding nanoparticles

Notably large is the SARS-CoV-2 spike protein, which is why scientists typically forge abridged models — to simplify the curation and application processes. Upon closer examination of the spikes, Kim and his team decided to remove a section near the bottom of the spikes.

To finish their vaccine, the team brought their shortened coronavirus spike together with nanoparticles of ferritin — a protein with iron — which was previously tested on humans. Before the coronavirus crisis, Powell had worked with these nanoparticles to curate a viable Ebola vaccine. In tandem with scientists from the SLAC National Accelerator Laboratory, the researchers used cryo-electron microscopy to obtain a 3D image of the spike ferritin nanoparticles — which verified the accuracy of the team's structure.

Scientists use 'pseudo-coronavirus,' avoid biohazard lab

The mouse tests involved comparing shortened spike nanoparticles to four different potentially effective variations. These include full spikes or partial spikes without nanoparticles, nanoparticles with full spikes, and a vaccine holding only the specific spike section used to bind cells during infection.

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Testing their vaccines' effectiveness would have called for a Biosafety Level 3 lab, so the researchers took the experimental shortcut of using a safer, pseudo-coronavirus modified to carry the same "crown" spikes.

Nanoparticle vaccines substantially raised antibody levels

The researchers monitored levels of neutralizing antibodies to find each vaccine's potential effectiveness. Antibodies are blood proteins the body produces in response to antigens — antibodies capable of neutralizing are the subset of antibodies capable of working to stop the virus from successfully infecting a host cell, according to the Stanford blog post.

Both of the two nanoparticle vaccine candidates increased neutralizing antibody levels — to at least twice the level seen in people who have had the COVID-19 illness, with only one dose. Additionally, the shortened spike nanoparticle vaccine enabled a significantly higher neutralizing response than the full or binding spike — or non-nanoparticle — vaccines.

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Fusion Medical Animation Coronavirus
A 2020 computer animation of the coronavirus spikes. Source: Fusion Medical Animation / Unsplash

Rapid COVID-19 vaccine pace is 'unprecedented'

With the second dose, mice who were exposed to the shortened spike nanoparticle vaccine experienced the highest observed levels of the crucial neutralizing antibodies.

In review of this project, Powell said the time from inception to the initial mouse studies was roughly four weeks. "Everybody had a lot of time and energy to the same scientific problem," she explained. "It is a very unique scenario. I don't really expect I'll ever encounter that in my career again."

"What's happened in the past year is really fantastic, in terms of science coming to the fore and being able to produce multiple different vaccines that look like they're showing efficacy against the virus," added Kim. "It normally takes a decade to make a vaccine, if you're even successful. This is unprecedented."

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Nanoparticle vaccine may be unnecessary

While the team's novel vaccine is designed for populations experiencing difficulty accessing the other, center-stage coronavirus vaccines, it's not impossible — in light of the speed at which the other vaccine candidates came to fruition — that the world won't need the nanoparticle COVID-19 vaccine.

If the nanoparticle vaccine proves superfluous, then the researchers stand poised to begin again and develop a more universal coronavirus vaccine — one capable of immunizing people against SARS-CoV-1, MERS, SARS-CoV-2, in addition to future coronaviruses possibly lying in wait.

Complex global issues call for complex solutions

"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," added Kim. "This coronavirus vaccine is part of work we're already doing — developing vaccines that are historically difficult or impossible to develop, like an HIV vaccine — and I'm glad that we're in a situation where we could potentially bring something to bear if the world needs it."

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It's easy to think of the coronavirus crisis as something monolithic — a singular antagonist requiring one key counterstrike to defeat, like the head of a snake. But here as elsewhere, the reality of viruses is more nuanced. Constantly evolving and mutating as it rips through a population of people who exist in a wide scatterplot of economic instability. Even if the Pfizer/BioNTech, Moderna, and other COVID-19 vaccines currently undergoing rollout are ultimately deemed an adequate response to the pandemic, the complex realities of coexisting viruses — compounded by wealth disparity worldwide — call for dynamic, unconventional thinking in developing vaccines.

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