WASHINGTON: An experimental vaccine that stimulates the production of specific proteins could be effective against the new coronavirus that causes Covid-19, according to a study conducted in mice.
Scientists at Ohio State University in the US manipulated a natural cellular process to increase the levels of two proteins used by the virus to infect other cells, packaged the protein booster instructions into nanoparticles, and injected them into mice.
Within a month, the mice had developed antibodies against the SARS-CoV-2 virus, according to the study published Wednesday in the journal Advanced Materials.
The technique involves altering specific sequences of messenger RNA, molecules that translate genetic information into functional proteins, the researchers said.
While these sequences are not translated into proteins, the researchers changed their structures to promote higher than usual protein levels.
The sequences are known as untranslated regions or UTRs.
Although phase 3 clinical trials of accelerated Covid-19 vaccine candidates are in progress, Yizhou Dong, associate professor at Ohio State University, said his laboratory platform offers a potential alternative.
“If current vaccines work well, that’s wonderful. In case the field needs it, then it is an option. It worked as a vaccine is expected to do, and we can scale this up very quickly,” Dong said.
“For now, it is a proof of concept: we have shown that we can optimize a messenger RNA sequence to enhance protein production, produce antigens and induce antibodies against those specific antigens,” he said.
The crux of the method is typical of vaccine development: using fragments of a pathogen’s structure to produce an antigen, the foreign substance that triggers an adequate immune response, and finding a safe way to get it into the body.
However, the technique takes antigen design to a new level through the use of messenger RNA UTRs, Dong said.
His laboratory worked with the two UTRs that define the beginning and end of protein assembly, functioning as regulators of that process and influencing how the resulting protein interacts with others.
UTRs themselves are chains of nucleotides, the molecules that make up RNA and DNA, the researchers said.
“For our application, we tried to optimize UTRs to improve the protein production process. We wanted to produce as much protein as possible, so that we could deliver a small dose of messenger RNA that produces enough antigen to induce antibodies against the virus,” said Dong . said.
The team experimented with two possible antigens that the new coronavirus is known to use to cause infection: a spike protein on its surface and a receptor-binding domain.
The domain is a component of the spike protein that the virus uses to make its way into host cells, a necessary step in making copies of itself.
Both are used in other candidates for the SARS-CoV-2 vaccine, the researchers said.
After manipulating the messenger RNA of these two proteins, the team encased them in lipid nanoparticles previously developed in Dong’s lab.
They injected mice with the experimental vaccine and gave them a booster two weeks later.
One month after the first injection, the immune cells of the mice had taken up the antigens of the two proteins and had developed antibodies against them.
“It takes the immune system some time to process antigens and make cells produce antibodies. In this study, we detect antibodies after 30 days,” Dong added.
Scientists at Ohio State University in the US manipulated a natural cellular process to increase the levels of two proteins used by the virus to infect other cells, packaged the protein booster instructions into nanoparticles, and injected them into mice.
Within a month, the mice had developed antibodies against the SARS-CoV-2 virus, according to the study published Wednesday in the journal Advanced Materials.
The technique involves altering specific sequences of messenger RNA, molecules that translate genetic information into functional proteins, the researchers said.
While these sequences are not translated into proteins, the researchers changed their structures to promote higher than usual protein levels.
The sequences are known as untranslated regions or UTRs.
Although phase 3 clinical trials of accelerated Covid-19 vaccine candidates are in progress, Yizhou Dong, associate professor at Ohio State University, said his laboratory platform offers a potential alternative.
“If current vaccines work well, that’s wonderful. In case the field needs it, then it is an option. It worked as a vaccine is expected to do, and we can scale this up very quickly,” Dong said.
“For now, it is a proof of concept: we have shown that we can optimize a messenger RNA sequence to enhance protein production, produce antigens and induce antibodies against those specific antigens,” he said.
The crux of the method is typical of vaccine development: using fragments of a pathogen’s structure to produce an antigen, the foreign substance that triggers an adequate immune response, and finding a safe way to get it into the body.
However, the technique takes antigen design to a new level through the use of messenger RNA UTRs, Dong said.
His laboratory worked with the two UTRs that define the beginning and end of protein assembly, functioning as regulators of that process and influencing how the resulting protein interacts with others.
UTRs themselves are chains of nucleotides, the molecules that make up RNA and DNA, the researchers said.
“For our application, we tried to optimize UTRs to improve the protein production process. We wanted to produce as much protein as possible, so that we could deliver a small dose of messenger RNA that produces enough antigen to induce antibodies against the virus,” said Dong . said.
The team experimented with two possible antigens that the new coronavirus is known to use to cause infection: a spike protein on its surface and a receptor-binding domain.
The domain is a component of the spike protein that the virus uses to make its way into host cells, a necessary step in making copies of itself.
Both are used in other candidates for the SARS-CoV-2 vaccine, the researchers said.
After manipulating the messenger RNA of these two proteins, the team encased them in lipid nanoparticles previously developed in Dong’s lab.
They injected mice with the experimental vaccine and gave them a booster two weeks later.
One month after the first injection, the immune cells of the mice had taken up the antigens of the two proteins and had developed antibodies against them.
“It takes the immune system some time to process antigens and make cells produce antibodies. In this study, we detect antibodies after 30 days,” Dong added.
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