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How Pfizer’s and Modern’s breakthrough COVID-19 vaccines work

As the weather cools, the number of infections in the COVID-19 pandemic rises sharply. Parliamentary officials have fought for pandemic fatigue, economic constraints and political disagreement and have fought to control the rising pandemic.

But now a shot of temporary analyzes from pharmaceutical companies Moderna and Pfizer / BioNTech has spurred optimism that a new type of vaccine made from messenger RNA, known as mRNA, can offer high levels of protection by preventing COVID-19 among people who have been vaccinated. .

Although unpublished, these preliminary reports have exceeded the expectations of many vaccine experts, including mine. Until the beginning of this year, I was working on developing vaccine candidates against Zika and dengue.

I am now coordinating an international effort to collect reports on adult patients with current or past cancers who have also been diagnosed with COVID-1


Promising preliminary results

Moderna reported that during the Phase 3 study of its vaccine candidate mRNA-1273, which registered 30,000 adult US participants, only five of the 95 COVID-19 cases occurred among those vaccinated, while 90 infections were identified in the placebo group.

This corresponds to an efficiency of 94.5 percent. None of the infected patients who received the vaccine developed severe COVID-19, while 11 (12 percent) of those who received placebo.

Similarly, the Pfizer-BioNTech vaccine candidate, BNT162b2, was 90 percent effective in preventing infection during the Phase 3 clinical trial, which enrolled 43,538 participants with 30 percent in the United States and 42 percent abroad.

How does the mRNA vaccine work?

Vaccines train the immune system to recognize the disease-causing part of a virus. Vaccines traditionally contain either attenuated viruses or purified signature proteins of the virus.

But an mRNA vaccine is different, because instead of getting the viral protein injected, a person receives genetic material – mRNA – that encodes the viral protein.

When these genetic instructions are injected into the upper arm, the muscle cells translate them to make the viral protein directly in the body.

This approach mimics what SARS-CoV-2 does in nature – but vaccine mRNA encodes only the critical fragment of the viral protein. This gives the immune system a preview of what the real virus looks like without causing disease.

This preview gives the immune system time to design powerful antibodies that can neutralize the real virus if the person is ever infected.

While this synthetic mRNA is genetic material, it cannot be passed on to the next generation. Following an mRNA injection, this molecule controls the protein production inside the muscle cells, which reaches peak levels in 24 to 48 hours and can last a few more days.

Why is it so quick to make an mRNA vaccine?

Traditional vaccine development, although well studied, is very time consuming and cannot respond immediately to new pandemics such as COVID-19.

For seasonal flu, for example, it takes about six months from identification of the circulating influenza virus strain to produce a vaccine. The candidate flu vaccine virus is cultured for approx. three weeks to produce a hybrid virus that is less dangerous and better able to grow in chicken eggs.

The hybrid virus is then injected into many fertilized eggs and incubated for several days to make multiple copies. The fluid containing the virus is then harvested from eggs, the vaccine viruses are killed, and the virus proteins are purified over several days.

The MRNA vaccines can overcome the obstacles by developing traditional vaccines, such as producing non-infectious viruses or producing viral proteins at medically demanding levels of purity.

MRNA vaccines eliminate much of the manufacturing process because instead of having viral proteins injected, the human body uses the instructions to make viral proteins itself.

Also, mRNA molecules are far simpler than proteins. For vaccines, mRNA is produced by chemical rather than biological synthesis, so it is much faster than conventional vaccines that need to be redesigned, scaled up, and mass-produced.

In fact, the mRNA code for a candidate vaccine test was within a few days of the genetic code of the SARS-CoV-2 virus becoming available. The most attractive thing is that when the mRNA vaccine tools become viable, mRNA can be quickly tailored to other future pandemics.

What are the problems with mRNA?

MRNA technology is not new. It was shown some time ago that when synthetic mRNA is injected into an animal, the cells can produce a desired protein. But progress remained slow.

This is because not only is mRNA notoriously unstable and easily degradable into smaller components, it is also easily destroyed by the human body’s immune system, making it very inefficient to deliver it to the target.

But in early 2005, researchers figured out how to stabilize mRNA and pack it into small particles to deliver it as a vaccine. The MRNA COVID-19 vaccines are expected to be the first to use this FDA-approved technology.

After a decade of work, the mRNA vaccines are now ready for evaluation. Doctors will keep an eye out for unintended immune reactions, which can be both helpful and harmful.

Why keep mRNA super cold?

The main challenge for the development of an mRNA vaccine remains its inherent instability because it is more likely to break apart above freezing temperatures.

Modification of mRNA building blocks and development of particles that can coconut it relatively safely have helped the mRNA vaccine candidates. But this new class of vaccine still requires unprecedented freezing conditions for distribution and administration.

What are the cooling requirements?

The Pfizer-BioNTech mRNA vaccine should be stored optimally at minus 94 degrees Fahrenheit (minus 70 degrees Celsius) and degraded in approximately five days at normal cooling temperatures slightly above freezing.

In contrast, Moderna claims that its vaccine can be maintained at most temperatures in the home or in a medical freezer for up to six months for shipment and long-term storage.

Moderna also claims that its vaccine can remain stable at standard refrigerated conditions of 36 to 46 degrees Fahrenheit (2 to 8 degrees Celsius) for up to 30 days after thawing within six months shelf life.

Not surprisingly, Pfizer is also developing shipping containers that use dry ice to address shipping restrictions. The conversation

Sanjay Mishra, Project Coordinator and Personnel Researcher, Vanderbilt University Medical Center, Vanderbilt University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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