“Plug and Play” mRNA technology works fast, updating vaccines in months

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The COVID-19 vaccines made by Pfizer and Moderna use messenger RNA (mRNA) technology, which allows scientists to test, deliver and modify the vaccines quickly. The ability to adapt quickly is on full display this summer.

On June 28, as Omicron BA.5 became the predominant COVID-19 variant in the United States, the U.S. Food and Drug Administration (FDA) recommended that Pfizer and Moderna update their mRNA booster shots to target the Omicron BA.4/BA.5 variants for a potential fall rollout. The updated vaccine is called a “bivalent” vaccine, meaning it would target both the original coronavirus strain and the latest Omicron subvariants.

A month later, on July 29, the federal government announced plans to purchase 66 million doses of a bivalent COVID-19 vaccine from Moderna, and 105 million doses from Pfizer. If the FDA and Centers for Disease Control and Prevention (CDC) review and authorize the updated vaccines, the bivalent vaccines could be available as soon as late September.

Coronavirus or sars-cov-2 virus cell with messenger RNA or mRNA and syringe on blue background 3D rendering illustration with copy space. Vaccination or vaccine, immunity, pandemic, science, medicine, medical technology concept.

This lightning-fast turnaround is made possible by the speed of “plug and play” mRNA technology. mRNA is a genetic material that tells our cells how to make specific proteins. After decades of research, scientists have learned to mimic this process to create vaccines that teach our cells how to make a specific protein from a virus. Once our body identifies a foreign protein (for example, COVID-19’s “spike” protein) it mounts an immune response, creating antibodies to fight off the foreign protein. Our immune system cells remember the invading foreign protein if they see it again in the future.

mRNA speed

Many laboratories can now rapidly determine the genetic makeup of a virus, called the “genome.” Once the genome is identified, scientists can plug it into the vaccine-making process and quickly produce a new or updated mRNA vaccine. On Jan. 11, 2020, scientists in China made the genome of SARS-CoV-2 (the virus that causes COVID-19) publicly available. Within two days, Moderna designed an mRNA vaccine that would tell our cells to make the spike protein found in the virus. Within 26 days Moderna had its first batch of vaccine. And March 16—just 65 days after the virus’ genome became known, Moderna started clinical trials.

After completing all three phases of clinical trials, Pfizer and Moderna’s vaccines were authorized for emergency use in the United States in December 2020, less than a year after the genome was identified. The vaccines have proven to be safe and extremely effective. During May of 2021, 99.9% of people hospitalized with COVID-19 had not been vaccinated. In addition, of the more than 18,000 people in the United States who died from COVID-19 during that month, only 150 (or 0.8%) had been fully vaccinated.

A traditional flu vaccine, on the other hand, requires growing a virus in chicken eggs, so it takes at least six months to produce enough vaccine for the nation’s population. Because the flu virus mutates from year to year, producing multiple strains globally, scientists must decide which strain to target for vaccines months before flu season begins every fall. This is one of the reasons flu vaccines, although still critical to preventing severe illness, can be less effective from year to year and are often less than 50% effective in preventing infection.

Early mRNA history

Scientist first discovered mRNA in 1961 and have been working to develop mRNA vaccines since the 1980s. One of the challenges they faced is that mRNA is an unstable molecule. When mRNA is injected into a cell, the cell can quickly reject and destroy it.

It wasn’t until the 1990s that real headway was made using “fatty droplets” that wrapped and protected mRNA, thus making it more stable and able to enter cells without being rejected. This technology paved the way for today’s mRNA vaccines to become a reality. Without this modification, the mRNA would not have survived long enough to teach our cells to build proteins, and mRNA vaccines would not exist.

Incidentally, the fact that mRNA is such an unstable molecule is thought to be one of the reasons it’s safe. Our cells break down mRNA within a few days of receiving a vaccine, and the spike protein may remain for a few weeks before breaking down. All that remains after the spike protein breaks down are the antibodies we built and the memory-B cells that are prepared to fight the virus if the spike protein returns.

mRNA vaccines over time

The first mRNA vaccine tested in mice in the 1990s targeted the flu virus. Technological advances led to an mRNA vaccine for rabies that were tested in humans for the first time in 2013. mRNA vaccines have also been developed for the Ebola and Zika viruses, although these have not yet been approved by the FDA.

Moderna, a young company whose name is a combination of “modified” and “RNA,” had an mRNA flu vaccine in clinical trials in 2015. That vaccine has not yet been approved by the FDA. It wasn’t until December 2020, less than a year into the COVID-19 pandemic, that an mRNA vaccine became available for use in the United States.

Current developments

As the pandemic has evolved, the virus that causes COVID-19 has rapidly mutated to evade the immunity we get from infections and vaccines, regardless of whether it’s an mRNA vaccine or not. The Omicron spike protein alone has 30 mutations since the vaccines were first developed to combat the original virus strain.

It’s not yet known what variant will be predominant in the coming months. Nor do we know how effective a modified bivalent vaccine targeting Omicron BA.4/BA.5 will be. But the potential for updating a vaccine and making it available within a few months is an amazing accomplishment of modern science.