A new type of vaccine provides protection against a variety of SARS-like betacoronaviruses, including SARS-CoV-2 variants, in mice and monkeys, according to a study led by researchers in the laboratory of Caltech‘s Pamela Bjorkman, the David Baltimore Professor of Biology and Bioengineering.
Betacoronaviruses, including those that caused the SARS, MERS, and COVID-19 pandemics, are a subset of coronaviruses that infect humans and animals. The vaccine works by presenting the immune system with pieces of the spike proteins from SARS-CoV-2 and seven other SARS-like betacoronaviruses, attached to a protein nanoparticle structure, to induce the production of a broad spectrum of cross-reactive antibodies. Notably, when vaccinated with this so-called mosaic nanoparticle, animal models were protected from an additional coronavirus, SARS-CoV, that was not one of the eight represented on the nanoparticle vaccine.
"Animals vaccinated with the mosaic-8 nanoparticles elicited antibodies that recognized virtually every SARS-like betacoronavirus strain we evaluated," says Caltech postdoctoral scholar Alexander Cohen (PhD ‘21), co-first author on the new study. "Some of these viruses could be related to the strain that causes the next SARS-like betacoronavirus outbreak, so what we really want would be something that targets this entre group of viruses. We believe we have that."
The research appears in a paper in the journal Science on July 5.
"SARS-CoV-2 has proven itself capable of making new variants that could prolong the global COVID-19 pandemic," says Bjorkman, who is also a Merkin Institute Professor and executive officer for Biology and Biological Engineering. "In addition, 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."
Such broad protection is needed, Bjorkman says, "because we can‘t predict which virus or viruses among the vast numbers in animals will evolve in the future to infect humans to cause another epidemic or pandemic. 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."
How it works: A vaccine composed of spike domains from eight different SARS-like coronaviruses
The vaccine technology to attach pieces of a virus to protein nanoparticles was developed initially by collaborators at the University of Oxford. The basis of the technology is a tiny cage-like structure (a "nanoparticle") made up of proteins engineered to have "sticky" appendages on its surface, upon which researchers can attach tagged viral proteins. These nanoparticles can be prepared to display pieces of one virus only ("homotypic" nanoparticles) or pieces of several different viruses ("mosaic" nanoparticles). When injected into an animal, the nanoparticle vaccine presents these viral fragments to the immune system. This induces the production of antibodies, immune system proteins that recognize and fight off specific pathogens, as well as cellular immune responses involving T lymphocytes and innate immune cells.
In this study, the researchers chose eight different SARS-like betacoronaviruses—including SARS-CoV-2, the virus that has caused the COVID-19 pandemic, along with seven related animal viruses that could have potential to start a pandemic in humans—and attached fragments from those eight viruses onto the nanoparticle scaffold. The team chose specific fragments of the viral structures, called receptor-binding domains (RBDs), that are critical for coronaviruses to enter human cells. In fact, human antibodies that neutralize coronaviruses primarily target the virus‘s RBDs.
The idea is that such a vaccine could induce the body to produce antibodies that broadly recognize SARS-like betacoronaviruses to fight off variants in addition to those presented on the nanoparticle by targeting common characteristics of viral RBDs. This design comes from the idea that the diversity and physical arrangement of RBDs on the nanoparticle will focus the immune response toward parts of the RBD that are shared by the entire SARS family of coronaviruses, thus achieving immunity to all. The data reported in Science today demonstrates the potential efficacy of this approach.