New type of vaccine using RNA can help defeat COVID-19

Courtesy Sanjay Misula, Vanderbilt University And Robert Carnahan, Vanderbilt University

A century ago, July 26, 1916, A viral disease has spread Through New York. Within 24 hours, new cases of polio have increased by more than 68%. The outbreak killed more than 2,000 people in New York City alone. Around the United States, polio killed about 6,000 people in 1916 and paralyzed thousands.

Scientists had already identified the poliovirus, but vaccine development took another 50 years. The vaccine has eradicated polio in the United States. In less than 10 years. Vaccine is one of The most effective modern disease fighting tools.

At the time of writing, the rapidly prevalent COVID-19 is already infected Nearly half a million people worldwide, And killed more than 22,000 patients. There is an urgent need for vaccines to prevent it Infects and kills millions of people. However, traditional vaccine development, on average, 16 years.

So how can scientists quickly develop SARS-CoV-2 vaccines?

As an immunologist, we They are trying to accelerate the development of vaccines and antibody therapeutics. Currently developing a new vaccine candidate for Zika and successfully developing a potential protective vaccine Antibody-based therapy -In 90 days-stop the viral disease. The “sprint” of such a fast track is Pandemic Protection Platform Program Operated by the U.S. Department of Defense Advanced Research Institute of Defense, it helps identify and deploy protective antibody treatments against SARS-CoV-2 and other virus outbreaks. Currently, our other colleagues are working on promoting a new type of vaccine for COVID-19.

Introduction to vaccines

Vaccines train the body’s immune system to recognize several characteristic viral proteins called antigens. SARS-CoV-2, like other coronaviruses, Spike like a crown on its surface. There is Three proteins on the surface of these viruses: Envelope, membrane, spike. Encapsulate RNA strands. This RNA molecule carries the genetic instructions that make up the virus.

However, viruses do not create their own components. Instead, the coronovirus is transmitted to the lungs and possibly other respiratory cells, Spike protein. Once inside, viral RNA becomes part of the host cell’s protein production machinery, producing new copies of viral proteins and RNA, and then reassembling to thousands of new viruses. Spread the disease.

Therefore, one way to stop the disease is to stop the virus from entering cells. Vaccines do this by training the body to identify and attack the virus before it can infect healthy human cells.

vaccine Essentially a pure preparation of one or more major components of the virus (envelopes, spikes, membrane proteins, etc.), which are injected into the body and provide a preview of the virus without causing disease to the immune system. This preview tells the immune system to look for and attack viruses that contain certain proteins when the actual virus emerges.

However, the development of vaccines based on viral proteins has been in progress for years DecadesFor rotavirus. Protein-based vaccines require large-scale production of viral proteins in facilities that can guarantee purity. Propagating the virus and purifying the protein on a medically acceptable pharmaceutical scale can take several years. In fact, for some of the recent epidemics, such as AIDS, Zika and Ebola, no vaccine is effective to date.

How to quickly make a new type of vaccine

To more quickly create an effective vaccine against unprecedented and rapidly spreading viruses such as SARS-CoV-2, Vanderbilt Researcher And use alternative approaches elsewhere. In one approach, instead of proteins, a new generation of vaccines, called mRNA vaccines, executes the molecular instructions to create proteins.

Instead of a standard vaccine that immunizes using viral proteins, mRNA vaccines provide a synthetic mRNA for the virus, which the host body uses to produce the viral protein itself.

The biggest advantage of mRNA vaccines is that they eliminate the need to produce pure viral proteins. This can save months or years to standardize and launch mass production.

mRNA vaccines basically mimic the natural infection of the virus, but contain only a short synthetic version of the viral mRNA, encoding only the antigenic protein. The mRNA used for vaccination can be used safely because it does not become part of the person’s chromosome. Such mRNA vaccines are safer than attenuated virus or protein based vaccines because there is no risk of activating or contaminating the injected virus.

COVID-19 mRNA vaccine tested

Using this strategy, biotechnology company Moderna Inc. announced on February 24 that it had developed rapidly. An COVID-19 mRNA vaccine called mRNA-1273Ready for clinical trials in humans. This vaccine candidate Union for fashion innovationIn collaboration with the National Institute of Allergy and Infectious Diseases. mRNA-1273 encodes a stable form of the SARS-CoV-2 spike protein.

The idea of ​​using the mRNA to read instructions and ask the human body to produce viral proteins is not new. researcher Almost 20 years ago, it was demonstrated that externally supplied mRNA was translated into the encoded protein. However, mRNA was not a very stable molecule, which prevented these mRNA vaccines from becoming a reality. The mRNA-1273 vaccine being developed today uses chemical modification to stabilize the mRNA and uses liquid nanoparticles to package it into an injectable form.

RNA-based antibodies

Scientists are using mRNA as a drug that can be administered intravenously, in addition to using it as a vaccine. In this case, the mRNA encodes an antibody protein known to attack the virus. So, instead of giving patients a protein antibody, doctors can instead instruct them to make an mRNA injection and make a copy of the antibody protein that fights their disease.

Effective antibodies are ready Identified By screening for survivors of the disease. However, producing such antibodies therapeutically often faces the hurdles of low yield, inefficient purification, and improper protein modification.

The effectiveness of such a strategy has already been demonstrated by James Crowe’s team Here in Vanderbilt. In animal studies, previously isolated antibodies from chikungunya survivors, an urgent mosquito-borne tropical virus infection causing chronic and debilitating joint pain and arthritis encoded as mRNA Given to mice. Antibodies encoded by mRNA protected mice from infections and virus-related arthritis and created protective antibodies in macaques. mRNA-based antibodies are currently Clinical trial.

Similarly, Specific antibodies to SARS-CoV-2 have been isolated From COVID-19 survivors. The most effective genetic instruction for anti-coronavirus antibodies can be encoded as mRNA. The antibodies encoded by these mRNAs can be used to treat patients in need of emergency treatment.

There are some promising new approaches, all of which are still . Our best protection against COVID-19 still lies in disease prevention and containment. Until a good vaccine against SARS-CoV-2 is made, social distance and vigilance are our best weapons.

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Sanjay Misula, Postdoctoral pathologist, microbiology and immunology, Vanderbilt University And Robert Carnahan, Associate Professor of Pediatrics, Vanderbilt University

This article was republished from conversation Under Creative Commons license. Read Original work.