The millions of lives saved by mRNA vaccines show the old ways of making vaccines are not the final word. Another technique under exploration uses protein-carrying nanoparticles, with encouraging signs for universal flu vaccines and even against cancer. Now, we can add broad-spectrum coronavirus protection to that list.

New COVID-19 variants are appearing so fast we can't redesign vaccines against them. To end the pandemic, we probably need something that attacks common features of all SARS-CoV-2 strains. Even better would be if it also protects against related viruses such as SARS and MERS, collectively known as betacoronaviruses.

That's what Caltech's Professor Pamela Bjorkman hopes her team's nanoparticle carriers can provide. In the journal Science, the team reports on the effectiveness of the idea in animal trials.

“The fact that three betacoronaviruses—SARS-CoV, MERS-CoV, and SARS-CoV-2—have spilled over into humans from animal hosts in the last 20 years illustrates the need for making broadly protective vaccines," Bjorkman said in a statement. 

Rather than vaccinate against a single strain, this uses small randomly arranged pieces of the spike protein from seven animal betacoronaviruses, plus SARS-CoV-2, attached to protein structures. The combination is called a mosaic. 

The hope is that the immune system, confronted with eight different versions of the spike, will develop antibodies against all of them. This should make it unlikely any future virus in the family will find a way to make a spike the body can't recognize and attack quickly.

"Animals vaccinated with the mosaic-8 nanoparticles elicited antibodies that recognized virtually every SARS-like betacoronavirus strain we evaluated," said first author Dr Alexander Cohen. Crucially, this includes the original SARS, even though it was not one of the viruses whose spike was used.

The team vaccinated mice either using the full mosaic, a single strain of SARS CoV-2 alone, or with the carrier nanoparticle without the virus fragment. All the mice in the study were genetically modified to express the human ACE2 receptor, used by betacoronaviruses to gain access to cells.

The control mice vaccinated with the carrier particle alone all died. Those getting the SARS CoV-2 vaccine showed strong protection against COVID-19 infection, and some against the original SARS. However, the mosaic-8 mice not only survived infection with both, but they also didn't even appear to get sick, including when exposed to Omicron subvariants. Monkeys vaccinated with mosaic-8 also brushed off both SARS viruses.

If a body primed with mosaic-8 has protection against a whole different (and deadlier) virus, there are grounds to hope it will also be well suited to fighting a new and only slightly different COVID-19 variant.

“What we're trying to do is make an all-in-one vaccine protective against SARS-like betacoronaviruses regardless of which animal viruses might evolve to allow human infection and spread. This sort of vaccine would also protect against current and future SARS-CoV-2 variants without the need for updating,” Bjorkman explained. 

The idea of combining multiple viruses may seem obvious, but is only possible because of technology developed by Bjorkman's collaborators at the University of Oxford, which allows pieces of the virus to be stuck to cage-like protein nanoparticles. Sticky extensions on the nanoparticles hold onto bits of one or more viruses, making them particularly accessible to the immune system.

Phase 1 clinical trials of the mosaic-8 vaccine will be starting soon. Since the subjects will have already been vaccinated against SARS-CoV-2 or infected with the disease (it's hard to find volunteers who haven't), adjustments need to be made. In preparation, researchers are testing how animals that have been vaccinated with existing COVID-19 vaccines or infected respond to mosaic-8 compared to those previously unexposed to either.