Comprehensive protection: Researchers have developed a new broad-spectrum vaccine against coronaviruses that could even protect against future types of viruses. It contains protein fragments 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 do not change between species.
Corona viruses are very changeable and adapt rapidly to new hosts and circumstances through mutations – this is demonstrated by the current corona pandemic: over time, the SARS-CoV-2 coronavirus has formed numerous variants that are easier to transmit and affect the 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 leap to humans in the future, with the risk of a new pandemic.
However, this also means that classic vaccine development will always lag behind such viruses. As soon as a vaccine against one variant has been found, the next one appears.
Fragments of tips of different coronaviruses
This is precisely where a new type of vaccine comes into play: “We want to develop a well-rounded vaccine that protects against all SARS-like betacoronaviruses, regardless of the animal coronavirus that will spread to humans,” explains Pamela Bjorkman of 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.”
To achieve this broad-spectrum protection, Bjorkman’s team developed a vaccine whose core component is a nanoparticle made up 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 RaTG13 bat virus, a form of coronavirus that has been detected in pangolins and five other virus bats similar to the pandemic pathogen.
Small editable 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 attachment points that are the same for everyone. The defense should then form antibodies mainly against the parts of the viral protein that do not or hardly differ between the different corona viruses – and are therefore likely to be unlikely to be modified in future variants.
Indeed, preliminary studies of the Mosaic-8 vaccine showed that the immune system of mice produces more widely effective antibodies after vaccination. “These bind preferentially to the conserved epitopes of the binding site,” the researchers report.
Tests with mice and macaques were successful
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. The exciting thing: the vaccine did not contain a SARS protein fragment. The team wanted to find out if the protection is broad enough to neutralize even uncontained corona viruses.
The result: “The 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, the test animals that only received the narrow-spectrum variant of the SARS-CoV-2 vaccine were not protected against SARS and died.
Animals vaccinated with Mosaic-8, on the other hand, remained symptom-free even with SARS, the researchers report. As hoped, the broad-spectrum vaccine also proved effective against a coronavirus that was not contained in the vaccine.
Phase 1 human experimentation planned
According to the scientists, this shows that a combined vaccine against corona viruses can work. A vaccine based on the Mosaic-8 model could not only protect against new variants of pathogens known as SARS-CoV-2, but also against new corona viruses that spread to humans. “Some of these betacoronaviruses used in the vaccine could be closely related to the strain that is causing a new outbreak,” says Bjorkman.
“We therefore need something that protects against the whole group of viruses – and we believe we have found it now,” says the researcher. In the next phase, Bjorkman and his team want to test their Mosaic-8 vaccine in a Phase 1 human clinical trial. The first focus will be on the safety and tolerability of the vaccine. “The monkey tests have been extremely promising, so we are excited to support this next phase of clinical trials,” said Richard Hatchett, leader of the Coalition for Epidemic Preparedness Innovations (CEPI).
At the same time, scientists are planning further animal experiments. Among other things, the protective effect of the Mosaic 8 vaccine should also be examined in animals that have already been vaccinated with the common Covid vaccines. 19. 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)
Those: California Institute of Technology