November 18, 2020


Unlocking the potential of vaccines built on messenger RNA: The technology could help to boost immunity against cancer, influenza and much more. (Elie Dolgin, 10/16/19, Nature)

Brad Kremer had waited months to receive an experimental cancer vaccine called BNT122, during which time the melanoma on his skin had spread to his liver and spine. His back pain was getting worse, he was rapidly losing weight and new cancerous lesions kept appearing on his left thigh. "It was very scary," says Kremer, a 52-year-old sales representative from Acton, Massachusetts.

But within weeks of his first injection in March, Kremer could see that the vaccine was working. The coin-sized melanoma spots that popped up from his skin were now flat discolourations measuring millimetres across. "I was actually witnessing the cancer cells shrinking before my eyes," he says. Several doses later, his appetite has returned, his back pain has subsided and scans show that his cancer is continuing to retreat.

Kremer's dramatic response exemplifies the medical potential of vaccines built on messenger RNA. In this method, strings of lab-synthesized nucleotides train the immune system to recognize and destroy disease-causing agents -- be they cancer cells or infectious viruses.

Other ways of making vaccines can achieve the same therapeutic objective. But the potency, versatility, speed of manufacturing and low cost of mRNA make it an attractive platform for the rapid development and large-scale production of new or custom-made vaccines.

Early clinical results have demonstrated the technology's promise. Researchers at BioNTech in Mainz, Germany, the manufacturer of the cancer vaccine that Kremer is receiving, reported in 2017 that all of the first 13 people with advanced-stage melanoma to receive the personalized immunotherapy -- which is tailor-made to match the genetic profile of each person's cancer -- showed elevated immunity against the mutated bits of their tumours. As a result, these patients' risk of developing new metastatic lesions was significantly reduced1. For viral diseases, prophylactic vaccine candidates against rabies2 and pandemic influenza3 have each proved safe and induced protective antibody responses in healthy volunteers. In both cases, however, the antiviral effects waned after less than a year, suggesting that improvements are needed to provide more robust and long-lasting immunity.

"There's a lot of potential here," says John Mascola, director of the Vaccine Research Center at the US National Institutes of Health in Bethesda, Maryland. "It's still early in the development of these vaccines, but the platform has shown proof of concept."

How mRNA vaccines work so brilliantly and why they must be kept so cold (Sanjay Mishra, 11/18/20, The World)

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

But an mRNA vaccine is different, because rather than having 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 the SARS-CoV-2 does in nature -- but the vaccine mRNA codes only for 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 individual is ever infected.

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

Traditional vaccine development, although well studied, is very time-consuming and cannot respond instantaneously against novel pandemics such as COVID-19.

For example, with seasonal flu, it takes roughly six months from identification of the circulating influenza virus strain to produce a vaccine. The candidate flu vaccine virus is grown for about three weeks to produce a hybrid virus, which is less dangerous and better able to grow in hens' eggs. The hybrid virus is then injected into a lot of fertilized eggs and incubated for several days to make more copies. Then the fluid containing virus is harvested from eggs, the vaccine viruses are killed, and the viral proteins are purified over several days.

The mRNA vaccines can leapfrog the hurdles of developing traditional vaccines, such as producing noninfectious viruses or producing viral proteins at medically demanding levels of purity.

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

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

In fact, within days of the genetic code of the SARS-CoV-2 virus becoming available, the mRNA code for a candidate vaccine testing was ready. What's most attractive is that once the mRNA vaccine tools become viable, mRNA can be quickly tailored for other future pandemics.

Posted by at November 18, 2020 6:35 PM