Another universal coronavirus vaccine ready for human trials

As scientists frantically chase a rapidly mutating SARS-CoV-2 virus by attempting to update current COVID vaccines to better target circulating variants, a huge project is bubbling in the background. The goal is to create a universal coronavirus vaccine designed to generate such broad immunity that it will protect people against all currently circulating strains of SARS-CoV-2, as well as any future variants that have yet to appear. And there are a number of attractive candidates in the pipeline.

A new study published in the journal Science reports promising results from preclinical studies led by researchers at Caltech. The vaccine uses a new mosaic nanoparticle technology to protect not only against SARS-CoV-2, but also against the original SARS and several common cold coronaviruses.

The experimental vaccine targets a particular genus of coronaviruses called beta-coronaviruses. These are the most clinically relevant types of coronaviruses for humans, including SARS, MERS, SARS-CoV-2, and two coronaviruses associated with the common cold – OC43 and HKU1.

Pamela Bjorkman, a Caltech researcher leading the project, said generating broad immunity to the entire group of beta coronviruses should protect against new viruses that could emerge in the future. And with three dangerous viruses emerging from the beta-coronavirus family in the past 20 years, it’s crucial to anticipate what could be the next pandemic.

“What we’re trying to do is create an all-in-one vaccine that protects against SARS-like beta-coronaviruses, regardless of which animal viruses can evolve to allow for human infection and spread,” Bjorkman said. “This type of vaccine would also protect against current and future SARS-CoV-2 variants without the need for an update.”

The Caltech vaccine uses nanoparticle scaffolds to fix a number of different beta coronavirus fragments. The vaccine targets eight different beta-coronaviruses: SARS-CoV-2 and seven other beta-coronaviruses that currently only circulate in animals, but all of which have the potential to mutate into a form that could infect humans in the future.

The vaccine does not target the traditional coronavirus spike protein, but instead uses viral fragments called receptor binding domains (RBDs). These are parts of the virus that act as a sort of interface between the spike protein and ACE2 receptors in human cells. RBDs are like the anchor connecting the virus to the human receptor.

This infographic illustrates the new vaccine, composed of RBDs from eight different viruses.  The table shows the broad spectrum of SARS-CoV-2 variants and related coronaviruses against which the vaccine protects

This infographic illustrates the new vaccine, composed of RBDs from eight different viruses. The table shows the broad spectrum of SARS-CoV-2 variants and related coronaviruses against which the vaccine protects

Wellcome Leap, Caltech and Merkin Institute

And recent animal studies testing this new vaccine, called Mosaic-8, have shown impressive results. In a number of tests on mice and primates, the researchers found that the vaccine successfully protects against most beta-coronavirus strains.

Interestingly, the researchers tested the Mosaic-8 design against a nanoparticle loaded exclusively with a SARS-CoV-2 RBD. When mice were exposed to the original SARS virus, only the animals that received the Mosaic-8 vaccine survived. This suggests that the combination of eight different antigens may generate broad cross-protective immunity against different types of beta-coronaviruses.

“Animals vaccinated with the mosaic-8 nanoparticles elicited antibodies that recognized virtually every SARS-like betacoronavirus strain we evaluated,” noted co-author Alexander Cohen. “Some of these viruses could be related to the strain causing the next SARS-like beta-coronavirus outbreak, so what we really want is something that targets this whole group of viruses. We think we have that.”

Thanks to a major injection of funding from The Coalition for Epidemic Preparedness Innovations (CEPI), Mosaic-8 is on track to move into Phase 1 human trials very soon. Because it’s 2022 and most people in the world have already received a COVID-19 vaccine or have been previously infected with SARS-CoV-2, the researchers are first conducting animal studies to test the new vaccine in previously exposed animals.

“There have already been three serious coronavirus epidemics or pandemics in the twenty-first century – and COVID-19 continues to have a devastating impact on the health, society and economy of the world,” said Richard Hatchett, CEO of CEPI. “Creating vaccines that could provide broad protection against emerging COVID-19 variants and future coronavirus threats would not only help mitigate the damaging effects of another COVID-19-like pandemic, it could help reduce the time it takes and the funding spent on continuously updating vaccine formulations.”

Mosaic-8 is by no means the only universal coronavirus vaccine currently in development. There are as many as 10 different research groups working with different strategies to produce a coronavirus vaccine that protects against current and future variants.

For example, the US military reported successful preclinical results earlier this year when testing a unique ferritin nanoparticle with the capacity to hold 24 different coronavirus antigens. This research has already begun the first phase of human trials and results are expected soon.

The new study was published in the journal Science

Source: Caltech

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