Researchers report that mice vaccinated with hybrid peplomers resisted infection from several coronaviruses.
HHMI scientists are working with many colleagues around the world to combat the new coronavirus. They develop diagnostic tests, understand the basic biology of the virus, model epidemiology, and develop potential therapies and vaccines.We will be Share some stories of this work..
By mixing and matching viral protein pieces into a single vaccine, you can provide greater protection against coronavirus.
Like connecting Lego blocks, scientists can connect different parts of the “peplomer”, molecules protruding from the coronavirus like a pointed crown. A Vaccine containing spike components from four coronaviruses including SARS-COV-2Howard Hughes Medical Institute Hannah Gray Fellow David Martinez and colleagues, who protected mice from four viruses, and other related coronaviruses, reported June 22, 2021 in the journal. Science..
Martinez, an immunologist at the University of North Carolina at Chapel Hill, suggests that the success of the vaccine in mice suggests that a similar strategy in humans may provide protection from future outbreaks. The coronavirus circulates in animals from bats to livestock, but scientists have not yet determined the extent of its genetic diversity. They know that the virus can sometimes jump to people. In 2003, the outbreak of coronavirus caused an outbreak of SARS. The associated coronavirus caused an ongoing pandemic. Both of these viruses are very similar to the viruses that infect bats.
“The fact that there have been two coronavirus epidemics in the last two decades shows that this can continue to happen,” says Martinez. “We need to find a way to devise a vaccine that can mitigate the threat of these viruses.”
The findings of Martinez’s team are “an important step towards a pan-corona virus vaccine,” said Melanie Ott, a virologist at the Gladstone Virology Institute who was not involved in the study. She points out that the researchers’ “mix-and-match” approach is broadly protective against multiple coronaviruses in mice and appears to provide levels of protection that current vaccines cannot provide. ..
When COVID-19 began to spread around the world in early 2020, the world waited for a vaccine that could protect it from the disease-causing coronavirus. But even when safe and effective vaccines are available and vaccinations are initiated, scientists have warned that new variants could break through vaccine protection. So far, current coronavirus vaccines appear to be resistant to mutants. However, researchers around the world are working to produce vaccines that can protect against the undiscovered coronavirus.
Vaccines created by Moderna, Pfizer and BioNTech work by giving people’s cells a strand of messenger RNA. This mRNA serves as a template that cells use to produce the SARS-CoV-2 peplomer. Peplomers are harmless in their own right, but they activate the immune system and begin to make antibodies against it. Later, if the vaccinated person encounters SARS-CoV-2, their antibodies are already waiting for the virus and their bodies are ready to fight.
To explore the idea that a single vaccine can inoculate multiple coronaviruses, Martinez and his colleagues have created a new peaplomer that is not found in any virus.
“We took advantage of the fact that the coronavirus peplomer is modular,” says Martinez. Instead of creating the mRNA strand that encodes the entire spike protein, we created four different mRNAs, each with segments from three different coronavirus spikes. They selected segments from the 2003 SARS virus, the 2019 virus (SARS-CoV-2), and two bat coronaviruses that can infect human cells but have not yet caused an epidemic.First team Publish results May preprint server on bioRxiv.
Like the Lego minifigure with cowboy legs, Spider-Man’s torso, and astronaut’s helmet, each hybrid peplomer contained three protein parts from different coronaviruses. Despite the mismatch, the mouse immune system still recognized these reshuffled proteins. After inoculating mice with the hybrid spike vaccine, animals produced effective antibodies against each component spike protein.
Inoculated mice were protected from the coronavirus whose peplomer subunit was contained in the vaccine. It was also resistant to two other viruses, including B.1.351 (now known as the “beta” variant). Martinez says the findings stimulate optimism about the team’s strategy, as it suggests that the antibodies produced by the hybrid spike vaccine can protect against a wide assortment of potential coronaviruses.
Proof of concept
Martinez’s team’s vaccine used the same mRNA technology that led to the success of the Moderna and Pfizer-BioNTech vaccines. mRNA is easy to produce, so once scientists find the optimal combination of peplomer proteins, mass production should be easy. However, before the vaccine moves to human testing, the Martinez team will conduct studies in larger animals to verify its safety and efficacy. These animal studies are still in the planning stages, so human testing may still be months away.
Although the inoculated mice were not protected from all types of coronavirus, the vaccine was very effective against the subgroup “Salvecovirus”, which included SARS and SARS-CoV-2. Mice also produced antibodies against the more distantly related coronavirus, including the MERS virus.
“We are trying to find a way to produce a vaccine that can protect against this subgroup, which is known to be at high risk,” says Martinez. “And preclinically, we have shown that this approach works.”
Dr. Martinez et al. “”Chimeric spike mRNA vaccine protects against salvecovirus challenge in mice.. ” Science.. Published online on June 22, 2021. doi: 10.1126 / science.abi4506
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