Nanoparticle vaccine protects against diverse coronaviruses in animal models

08 Aug 2022

All-in-one vaccine: Infographic illustrating the new vaccine, composed of fragments from eight different viruses. The table shows the broad spectrum of SARS-CoV-2 variants and related coronaviruses that the vaccine induces protection against. (Courtesy: Wellcome Leap, Caltech, Merkin Institute)

As the virus that causes COVID-19 evolves and spreads, scientists and clinicians continue developing innovative ways to combat SARS-CoV-2 by designing vaccines and therapeutics. In a recent study published in Science, researchers present a vaccine that, in animals, protects against a variety of betacoronaviruses – a family of viruses that includes those causing the SARS, MERS and COVID-19 pandemics.

The study was led by a California Institute of Technology research team directed by Pamela Bjorkman. Bjorkman says that designing a vaccine with broad protection against several viruses is important, considering that several SARS-like viruses have emerged in the past two decades.

“We can’t predict which virus or viruses among the vast numbers in animals will evolve in the future to infect humans to cause another epidemic or pandemic,” Bjorkman says in a Caltech press release. “What we’re trying to do is make an all-in-one vaccine protective against SARS-like betacoronaviruses regardless of which animal viruses might evolve to allow human infection and spread. This sort of vaccine would also protect against current and future SARS-CoV-2 variants without the need for updating.”

Mosaic vaccine provides broad protection

Bjorkman’s team designed a nanoparticle vaccine consisting of spike protein fragments from eight SARS-like betacoronaviruses, using vaccine technology initially developed by collaborators at the University of Oxford. In theory, when an immune system is exposed to spike protein fragments attached to this so-called “mosaic” nanoparticle vaccine, it will produce a broad spectrum of antibodies that respond to all viruses represented in the vaccine.

The researchers conducted experiments in mice genetically engineered to express the human ACE2 receptor, which is used by SARS-CoV-2 and related viruses to enter cells upon infection. They found that animals inoculated with the mosaic nanoparticle vaccine produced antibodies to all viruses with fragments in the vaccine.

Mice that received a vaccine containing a nanoparticle without spike protein fragments did not survive infection by SARS-CoV-2 or SARS-CoV (which caused the original SARS pandemic in the early 2000s). Those inoculated with a nanoparticle coated only in SARS-CoV-2 spike protein fragments only survived exposure to SARS-CoV-2. Mice vaccinated with the mosaic nanoparticle, however, not only survived exposure to SARS-CoV-2, but were also protected from SARS-CoV, which was not one of the eight betacoronaviruses incorporated into the vaccine.

The researchers conducted similar experiments in non-human primates using the mosaic nanoparticle vaccine. Again, the animals survived exposure to SARS-CoV-2 or SARS-CoV, and they showed little to no detectable infection.READ MORE

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Working with collaborators at the Fred Hutchinson Cancer Research Center, Bjorkman’s team found that the antibodies developed by non-human primates when vaccinated were in response to the most common elements of receptor-binding domains, such as spike proteins. This result, the researchers say, suggests that the mosaic vaccine could be effective against new variants of SARS-CoV-2 or animal SARS-like betacoronaviruses.

“Animals vaccinated with the [mosaic] nanoparticles elicited antibodies that recognized virtually every SARS-like betacoronavirus strain we evaluated,” says first author Alexander Cohen in a press statement. “Some of these viruses could be related to the strain that causes the next SARS-like betacoronavirus outbreak, so what we really want would be something that targets this entire group of viruses. We believe we have that.”

Next up: clinical trials

With the efficacy of the mosaic nanoparticle vaccine borne out in both laboratory and animal studies, Bjorkman and her collaborators are now preparing a Phase 1 clinical trial to evaluate the vaccine in humans. The trial will enrol people who have been vaccinated and/or previously infected with SARS-CoV-2. Animal model experiments will run in parallel with human studies to compare immune responses in animals previously vaccinated with a current COVID-19 vaccine to responses in animals that haven’t been exposed to the virus or received a vaccine.

Catherine Steffel is a science writer based in Madison, Wisconsin. Catherine was previously a PhD student contributor to Physics World.

from physicsworld.com     10/8/2022