‘LEGO-style’ vaccine protects mice against COVID, SARS, MERS and variants

“Rather than playing around with every new problematic variant,” Anthony Fauci told James Hamblin at The Atlantic, “it just makes sense for me to use all of our abilities to really go for a universal SARS-CoV vaccine. 2. ”

A group of researchers led by University of North Carolina immunologist David Martinez managed to vaccinate mice with an even better vaccine than what Fauci suggested to Hamblin: a vaccine that works against many coronaviruses, not just SARS-CoV-2 and its variants.

By combining pieces of spike proteins from several coronaviruses into one and delivering them via mRNA, the vaccine provided protection against SARS-CoV-2, classical SARS and two other coronaviruses.

The results “are an important step towards a pan-coronavirus vaccine,” Gladstone Institute of Virology virologist Melanie Ott, who was not involved in the study, told Howard Hughes Medical Institute (HHMI).

A universal weapon: Universal vaccines – vaccines that cover all variants of a virus, or all types of virus – are the most ardent desire of vaccinology.

Imagine, for example, a universal flu vaccine: protection against the shapeshifter flu in all its forms, no more guesswork each year, no more mistakes. (Once considered a pipe dream, one candidate passed Phase 1 trials last winter.)

SARS-CoV-2 currently mutates faster than the influenza virus, and although vaccines still seem to work against the newer variants, there are signs the virus is evolving to evade immunity.

The LEGO antigen: To create their vaccine, Martinez and his team took three proteins from the tips of 4 different coronaviruses: SARS-CoV, SARS-CoV-2 and two bat coronaviruses capable of infecting human cells, but did not still caused epidemics.

“We took advantage of the fact that the coronavirus spike protein is modular,” Martinez told HHMI. They then used these parts to assemble a new advanced protein, not found in nature.

The resulting immune system target – called an antigen – is akin to “a LEGO minifigure with the legs of a cowboy, the torso of Spider-Man and the helmet of an astronaut,” as HHMI puts it. so evocative way.

Using the same mRNA technique that fueled the extremely potent vaccines from Moderna and Pfizer, the team vaccinated mice with the LEGO-like spike protein.

Universal protection: The vaccinated mice were faced with a row of deadly coronaviruses, including the four viruses from which the antigen was made, as well as a few others.

The antibodies created by the vaccine provided broad protection against all of the “Sarbecoviruses” that were tested – the entire group of coronaviruses which includes SARS and SARS-CoV-2.

The mice were also protected against the two bat coronaviruses and two of the “variants of concern” of SARS-CoV-2, Alpha and Beta (originally found in Britain and South Africa).

Even more promising, the vaccine created antibodies that reacted to MERS, an extremely deadly camel coronavirus, which is not closely related to others – a hint that a pan-coronavirus vaccine may be possible.

Mice that were vaccinated with only the SARS-CoV-2 spike protein, instead of the LEGO-like combination, may have been infected with SARS and a bat coronavirus, Clinical OMICS reports.

The next steps: Of course, mice are do not people, and there is still work to be done before human clinical trials begin.

The team’s next step, still in the planning stage, will be studies on other larger animal models (such as monkeys) to test for safety and efficacy, before moving on to phase 1 trials. , which could take months.

Yet the need will not go away.

“The fact that we’ve had two coronavirus outbreaks in the past two decades tells us that this is something that can continue to happen,” Martinez said.

“We need to find ways to design vaccines that can mitigate the threat of these viruses. ”

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