mRNA vaccines: what milestone comes next
The Nobel Prize award should not have come as a surprise to the two researchers. Katalin Karikó and Drew Weissman had already won many prestigious prizes, so many predicted the Nobel Prize was imminent. The US edition of MIT Technology Review ranked the mRNA vaccines among the “Top 10 Breakthrough Technologies” of 2021. These vaccines made their big appearance in the corona pandemic, but they should not stand in the fight against SARS-CoV-2 remain.
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mRNA vaccines work differently
A look at the merit of Karikó and Weissman: Most vaccines train the immune system by delivering the pathogen against which they are intended to protect – either the entire pathogen or a crucial component. The mRNA vaccines work a little differently. They provide a genetic code that the body’s cells can translate into proteins. In the case of Covid-19, the vaccines contain mRNA that encodes the “spike” protein that protrudes from the outer surface of the virus. The body then produces copies of this protein, and the immune system learns to recognize it.
The idea of using mRNA in vaccines has been around for decades, but scientists encountered a major stumbling block early on. Antonio Regalado told part of this story in his 2021 piece on mRNA in MIT Technology Review. When researchers injected mRNA into mice, the animals became sick. “Their fur stands up. They lose weight and stop running around,” Weissman told Regalado. Larger doses proved fatal. “We quickly realized that the messenger RNA was not useful,” he said.
When foreign mRNA is injected into the body, the immune system detects a threat and triggers inflammation. Karikó and Weissman found that they could almost eliminate this problem by slightly changing the genetic code. When the pandemic broke out in 2020, scientists had already used their method to develop mRNA vaccines for other infectious diseases, so it was relatively easy to pivot to Covid-19.
What makes mRNA a game changer?
The vaccines are so easy to produce. When manufacturers wanted to update their Covid vaccines this fall, all they had to do was insert a new code. By exchanging different codes, they should be able to combat different pathogens.
Moderna has already filed an application for approval of an mRNA vaccine against respiratory syncytial virus (RSV), a cold-like illness that can be severe in infants and older adults. The company also has an mRNA flu vaccine in late-stage clinical testing. An interim analysis in September showed the vaccine performed better than traditional flu shots across all age groups, Moderna said. Pfizer is also testing an mRNA flu vaccine, as are Sanofi Pasteur and GlaxoSmithKline in collaboration with CureVac. Several of these companies are also working on combination vaccines that protect against Covid-19 and flu.
There are several reasons why several companies are focusing their mRNA efforts on flu. First, current flu vaccines rely on viruses grown in chicken eggs or cells, a laborious process that takes months. Using mRNA for flu vaccination would eliminate the need to grow the virus and speed up the process significantly. This could allow for a better match between the vaccine and circulating flu strains (because the strains could be selected closer to flu season) and a faster response in the event of a flu pandemic.
The other reason is that researchers can add mRNA for many different flu strains to create a vaccine that could provide broader protection. Last year, a team at the University of Pennsylvania tested an mRNA vaccine that contains antigens from all 20 known flu subtypes that infect people. In mice and ferrets, the vaccine protected against strains that matched the vaccine and against strains that did not. This year, the National Institutes of Health launched a clinical trial to test a different mRNA flu vaccine that doesn’t contain multiple antigens but is designed to trigger a response to a part of the virus that doesn’t change easily from year to year .
The flu is just the beginning
The list of diseases for which mRNA vaccines are being developed goes on and on: malaria, HIV, Zika virus, Epstein-Barr virus, cytomegalovirus, herpes, norovirus, Lyme disease, Nipah virus, C. difficile, Hepatitis C, leptospirosis, tuberculosis, shingles, acne, chlamydia and many others.
And it doesn’t stop there: mRNA could also be an effective tool for treating diseases, not just preventing them. It was originally intended as a therapeutic agent. mRNA-based cancer therapies have been tested for a decade. The idea is to provide mRNA that codes for proteins on the surface of the tumor. The immune system would then learn to recognize these antigens and can better detect and attack the cancer tissue.
Companies are also working on mRNA therapies for rare diseases, such as: B. Cystic fibrosis. People with this disease have mutations in a gene called CFTR (cystic fibrosis transmembrane conductance regulator). These mutations cause the CFTR protein, which helps water flow in and out of cells, to malfunction, resulting in sticky mucus that clogs the lungs and causes recurrent respiratory infections.
Vertex, in collaboration with Moderna, has developed an mRNA that is intended to be inhaled. Once in the lungs, the cells translate the code into functional CFTR. Late last year, the US FDA gave Vertex the green light to start a study testing mRNA for cystic fibrosis. Moderna has also initiated clinical trials testing treatments for methylmalonic anemia, a disease that affects liver function, and propionic anemia, a rare metabolic disorder.
Not all of these attempts will be successful, in fact many of them will probably be successful. But the mRNA stroke of luck will certainly lead to some successes. When Karikó and Weissman made their groundbreaking discovery in 2005, “I said to Kati that our phones would ring off the hook,” Weissman said in an interview with Boston University’s alumni magazine in 2021. “But nothing happened. We didn’t get a single one Call.” These days, it’s safe to assume that their phones won’t stop ringing.
(jl)
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