Betacoronaviruses, including those that caused the SARS epidemic, MERS, and COVID-19, are a group of coronaviruses that infect humans and animals. The vaccine works by introducing antibodies into fragments of spike protein from SARS-CoV-2 and seven other Sacacoronaviruses, such as SARS, attached to a protein nanoparticle structure, to produce a wide range of active antibodies. Significantly, when vaccinated with the so-called mosaic nanoparticle, animal models were protected from an additional coronavirus, SARS-CoV, which was not one of eight nanoparticle vaccines.
“Animals vaccinated with mosaic-8 nanoparticles have acquired antibodies that detect almost every type of betacoronavirus such as SARS that we have tested,” said Caltech postdoctoral scientist Alexander Cohen (PhD ’21), co-author and co-author of the new study. “Some of these viruses may be associated with the severity that causes the subsequent outbreak of betacoronavirus in SARS, so what we really want could be something that has targeted this group of viruses. We believe we have that.”
“SARS-CoV-2 has proven to be able to develop new species that could exacerbate the COVID-19 epidemic,” said Bjorkman, who is also a Professor of the Merkin Institute and chief executive officer of Biology and Biological Engineering. “Furthermore, the fact that three betacoronaviruses – SARS-CoV, MERS-CoV, and SARS-CoV-2 – have spread to humans from animals over the past 20 years demonstrates the need for more effective vaccines. “
The principle of the principle of attachment of viral fragments to protein nanoparticles was developed earlier by participants at Oxford University. The basis of technology is a tiny cage-like structure (“nanoparticle”) made of proteins that are made to have “sticky” additives on its surface, where researchers can attach viral proteins. These nanoparticles can be configured to display only fragments of one cell (homotypic “nanoparticles) or fragments of several different microbes (” mosaic “nanoparticles). When you inject an animal, the nanoparticle vaccine brings these pieces of the virus into the immune system. This triggers the production of antibodies, antibodies to recognize and fight off certain viruses, and immune responses including T lymphocytes and innate immune cells.
In this study, researchers selected eight different betacoronaviruses such as SARS – including SARS-CoV-2, the virus that caused the COVID-19 epidemic, and seven related animal viruses that could potentially trigger the epidemic in humans – and attach them to fragments of those eight bacteria in the nanoparticle scaffold. The team selected specific fragments of viral structures, called receptor-binding domains (RBDs), that are essential for coronaviruses to invade human cells. In fact, the human immune system weakens coronaviruses and targets viral RBDs.
The idea is that a vaccine could induce the body to produce antibodies that are more sensitive to betacoronaviruses such as SARS to fight diversity beyond what is presented in the nanoparticle by identifying the common features of RBD in the virus. This design stems from the idea that the diversity and classification of RBDs in the nanoparticle will focus on the immune response to the RBD components shared by the entire SARS coronavirus family, thus achieving universal immunity. Data reported in Science today demonstrate the effectiveness of this approach.
Designing experiments to measure the vaccine’s protection in mice
The vaccine (here called mosaic-8) is made up of RBDs from eight coronaviruses. Previous experiments conducted by the Bjorkman laboratory have shown that mosaic-8 induces mice producing antibodies that respond to a variety of coronaviruses in a laboratory setting (Cohen et al., 2021, Science). Led by Cohen, a new study aimed at building from this study to see if vaccination with the mosaic-8 vaccine can put the immune system in a living animal where there is a challenge (in other words, infection) with SARS-CoV-2 or SARS-CoV . .
The team performed three experimental sets on mice. In other words, they control the mice in the form of a blank nanoparticle cage without the pieces of virus attached. The second group of mice was injected with homotypic nanoparticle covered only in SARS-CoV-2 RBDs, while the third group of mice was injected with mosaic-8 nanoparticles. One goal of the experiment was to determine whether mosaic-8 vaccines would protect animals from SARS-CoV-2 at the same rate as SARS-CoV-2-homotypic vaccines; the second goal was to test for protection from the so-called “parasitic virus” – which was not represented by RBD in mosaic-8 nanoparticle. The mice used in the experiments were genetically engineered to produce a human ACE2 receptor, which is a receptor for the human cells used by SARS-CoV-2 and related viruses to gain access to cells during infection. In this model of animal challenge, unvaccinated mice die if they are infected with a betacoronavirus such as SARS, thus providing rigorous testing to test the immune system in humans.
Importantly, in collaboration with Jesse Bloom (PhD ’07) Fred Hutchinson Cancer Research Center, the team found that mosaic-8 antibodies target the most common RBDs in a variety of betacoronaviruses such as SARS – – the so-called “preserved” part of the RBD – thus provides evidence of a hypothetical approach in which the vaccine will be effective against new strains of SARS-CoV-2 or animal predacoronavirus such as SARS. In contrast, SARS-CoV-2 homopypic injections of the nanoparticle stimulate the immune system against specific RBD regions, suggesting that these vaccines may be protective against SARS-CoV-2 but not new species or potential animal viruses. .
The paper is entitled “Mosaic RBD nanoparticles protect the challenge with various sarbecoviruses in animal models.” Neeltje van Doremalen of the National Center for Disease and Infectious Diseases (National Health Centers) Rocky Mountain Laboratories is a first co-author and Cohen.
This pre-health goal certification study is sponsored by Wellcome Leap, and is based specifically on the initial development and evidence-based study studies sponsored at the beginning of the epidemic by Caltech’s Merkin Institute for Translational Medicine. Another ongoing coronavirus project in the Bjorkman team is supported by the Bill and Melinda Gates Foundation and the George Mason Fast Grants.
Source Journal Reference: Alexander A. Cohen, Neeltje van Doremalen, Allison J. Greaney, Hanne Andersen, Ankur Sharma, Tyler N. Starr, Jennifer R. Keeffe, Chengcheng Fan, Jonathan E. Schulz, Priyanthi N. P. Gnanapragasam, Leesa M. Kakutani, Anthony P. West, Greg Saturday, Yu E. Lee, Han Gao, Claudia A. Jette, Mark G. Lewis, Tiong K. Tan, Alain R. Townsend, Jesse D. Bloom, Vincent J. Munster, Pamela J. Bjorkman. Mosaic RBD nanoparticles protect against challenge by diverse sarbecoviruses in animal models. Science, 2022; DOI: 10.1126/science.abq0839
Read Also:Climate change focus: Scientists have discovered evidence of rising sea levels hidden in caves
