A complete coronavirus vaccine

Mosaic-8-Impfstoff

Comprehensive protection: Researchers have developed a new broad-spectrum coronavirus vaccine that may even protect against future types of viruses. It contains pieces of protein from eight different beta corona viruses and has been shown to be very effective in tests with mice and monkeys – even against corona viruses whose proteins are not contained in the vaccine. The reason: The combination vaccine promotes the formation of antibodies that primarily target parts of the viral protein that don’t change from species to species.

Corona viruses are very changeable and adapt quickly to new hosts and circumstances through mutations – this is demonstrated by the current corona pandemic: Over time, the coronavirus SARS-CoV-2 has formed numerous variants which are easier to transmit and affect our immune response in parts can undermine. A look at the animal kingdom also shows that there are countless other corona viruses that could make the jump to humans in the future – with the risk of a new pandemic.

However, this also means that the development of conventional vaccines will always lag behind these viruses. No sooner has a vaccine been found against one variant than the next appears.

Preliminary tests show that the Mosaic-8 vaccine elicits an antibody response even against uncontained viral variants. © Wellcome Leap/ Caltech, Merkin Institute

Spike fragments of different coronaviruses

This is exactly where a new type of vaccine comes in: “We want to develop a comprehensive vaccine that protects against all SARS-like betacoronaviruses – regardless of the animal coronavirus that then spreads to humans,” says Pamela Bjorkman from the California Institute of Technology. “At the same time, this type of vaccine could also protect against current and future variants of SARS-CoV-2 without us having to constantly adapt it.”

In order to achieve such broad-spectrum protection, Bjorkman’s team developed a vaccine whose central component is a nanoparticle consisting of a “sticky” carrier protein. Pieces of the viral spike protein are then mounted on its surface. In the current “Mosaic-8” test vaccine, these are the binding sites of eight different betacoronaviruses, including SARS-CoV2, the bat virus RaTG13, a form of coronavirus that has been detected in pangolins, and five other bat viruses similar to the pandemic pathogen.

Hardly Modifiable Attack Targets

The idea behind it: when our immune system comes into contact with so many different viral proteins, it looks for recognition markers and attack points that are the same for everyone. The defense should therefore form antibodies mainly against those parts of the virus protein which differ little or not between the different corona viruses – and which will therefore probably not be changed much in future variants.

Indeed, preliminary studies of the Mosaic-8 vaccine showed that the immune system of mice produced more broadly effective antibodies after vaccination. “These bind preferentially to conserved binding site epitopes,” the researchers report.

animal testing
The Mosaic-8 vaccine protected mice and monkeys against SARS-CoV-2 and against SARS. It has also elicited antibody reactions against various current variants of the pandemic pathogen.© Wellcome Leap/ Caltech, Merkin Institute

Successful tests with mice and macaques

For their current study, Bjorkman and his team vaccinated mice and macaques with the Mosaic 8 vaccine, an “empty” nanoparticle or nanoparticle containing only the SARS-CoV-2 spike protein. The animals were then infected with SARS-CoV-2 or its predecessor SARS. What’s exciting about it: The vaccine did not contain a SARS protein fragment. The team wanted to know if the protection is wide enough to neutralize even uncontained corona viruses.

The result: “Animals vaccinated with Mosaic-8 produced antibodies that recognized literally every SARS-like betacoronavirus we tested,” reports first author Alexander Cohen of Caltech. None of the animals infected with SARS-CoV-2 became ill. More importantly, test animals that received only the narrow-spectrum vaccine variant against SARS-CoV-2 were not protected against SARS and died.

Animals vaccinated with Mosaic-8, on the other hand, remained symptom-free even with SARS, as the researchers report. As hoped, the broad-spectrum vaccine was even effective against a coronavirus that was not contained in the vaccine.

Phase 1 human trial planned

According to scientists, this proves that a combined corona virus vaccine can work. A vaccine based on the Mosaic-8 model could not only protect against new variants of known pathogens such as SARS-CoV-2, but also against new corona viruses that spread to humans. “Some of these betacoronaviruses used for the vaccine could be closely related to the strain that causes a new epidemic,” says Bjorkman.

“So we need something that protects against this whole group of viruses – and we think we’ve now found it,” says the researcher. In the next step, Bjorkman and his team want to test their Mosaic 8 vaccine in a phase 1 clinical trial in humans. The first focus will be on the safety and tolerability of the vaccine. “Testing in monkeys has been extremely promising, so we are excited to support this next phase of clinical trials,” said Richard Hatchett, head of the Coalition for Epidemic Preparedness Innovations (CEPI).

At the same time, scientists are planning new animal experiments. Among other things, the protective effect of the Mosaic 8 vaccine should be examined in animals that have already been vaccinated with common Covid.19 vaccines. The main question here is whether the immune system can relearn: can it then produce antibodies that have a broader effect instead of the relatively specialized antibodies? (Science, 2022; doi: 10.1126/science.abq0839)

Source: California Institute of Technology

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