The two most effective coronavirus vaccines developed in the United States – the Pfizer and Moderna vaccines – are both mRNA vaccines. The idea of using genetic material to produce an immune response has opened up a world of research and potential medical uses far beyond the reach of traditional vaccines. Deborah Fuller is a microbiologist at University of Washington who has been studying genetic vaccines for more than 20 years. The Conversation spoke to him about the future of mRNA vaccines for The Conversation Weekly podcast.
Below are excerpts from that conversation that have been edited for length and clarity.
How long have gene-based vaccines been in development?
This type of vaccine has been in the works for about 30 years. Nucleic acid vaccines are based on the idea that DNA makes RNA then RNA makes proteins. For a given protein, once we know the sequence or genetic code, we can design an mRNA or DNA molecule that prompts a person’s cells to start making it.
When we first thought of this idea of putting genetic code into someone’s cells, we were studying both DNA and RNA. mRNA vaccines didn’t work very well at first. They were unstable and elicited quite strong immune responses that were not necessarily desirable. For a very long time, DNA vaccines took center stage, and the very first clinical trials involved a DNA vaccine.
But about seven or eight years ago, mRNA vaccines started to take the lead. Researchers solved many problems – including instability – and discovered new technologies to deliver mRNA into cells and ways to modify the coding sequence to make vaccines much safer to use in humans.
With these issues resolved, the technology was truly poised to become a revolutionary tool for medicine. It was just when COVID-19[female[feminine to hit.
What makes nucleic acid vaccines different from traditional vaccines?
Most vaccines induce antibody responses. Antibodies are the main immune mechanism that blocks infections. When we started to study nucleic acid vaccines, we discovered that since these vaccines are expressed in our cells, they were also very effective in inducing a T cell response. This discovery really sparked additional thinking about the how researchers could use nucleic acid vaccines not just for infectious diseases, but also for immunotherapy to treat cancers and chronic infectious diseases – like HIV, hepatitis B and herpes – as well as autoimmune diseases and even for gene therapy. .
How can a vaccine treat cancers or chronic infectious diseases?
T cell responses are very important in identifying cells infected with chronic diseases and aberrant cancer cells. They also play an important role in eliminating these cells from the body.
When a cell becomes cancerous, it begins to produce neoantigens. In normal cases, the immune system detects these neo-antigens, recognizes that something is wrong with the cell, and eliminates it. The reason some people develop tumors is that their immune system is not quite able to eliminate the tumor cells, so the cells spread.
With an mRNA or DNA vaccine, the goal is to make your body better able to recognize the very specific neo-antigens that the cancer cell has produced. If your immune system can recognize and see them better, it will attack the cancer cells and eliminate them from the body.
This same strategy can be applied to the elimination of chronic infections such as HIV, hepatitis B and herpes. These viruses infect the human body and remain in the body forever unless the immune system eliminates them. In the same way that nucleic acid vaccines can train the immune system to eliminate cancer cells, they can be used to train our immune cells to recognize and eliminate chronically infected cells.
What is the status of these vaccines?
Some of the very first clinical trials of nucleic acid vaccines took place in the 1990s and involved cancer, particularly melanoma.
Today, there are a number of mRNA clinical trials underway for the treatment of melanoma, prostate cancer, ovarian cancer, breast cancer, leukemia, glioblastoma and other cancers. others, and there have been promising results. Moderna recently announced promising results with its Phase 1 trial using mRNA to treat solid tumors and lymphomas
There are also many ongoing DNA cancer vaccine trials, as DNA vaccines are particularly effective at inducing T-cell responses. A company called Inovio recently demonstrated a significant impact on cervical cancer. uterus caused by human papillomavirus in women using DNA vaccine.
Can nucleic acid vaccines treat autoimmune diseases?
Autoimmune diseases occur when a person’s immune cells actually attack part of their own body. An example of this is multiple sclerosis. If you have multiple sclerosis, your own immune cells attack myelin, a protein that covers the nerve cells in your muscles.
The way to eliminate an autoimmune disease is to modulate your immune cells to prevent them from attacking your own proteins. Unlike vaccines, which aim to stimulate the immune system to better recognize something, treatment for autoimmune diseases seeks to weaken the immune system so that it stops attacking something it shouldn’t. Recently, researchers created an mRNA vaccine encoding a myelin protein with slightly altered genetic instructions to prevent it from stimulating immune responses. Instead of activating normal T cells that increase immune responses, the vaccine caused the body to produce regulatory T cells that specifically suppressed only T cells that attacked myelin.
Other applications of the new vaccine technology?
The latest application is actually one of the very first things researchers thought about using DNA and mRNA vaccines for: gene therapy. Some people are born without certain genes. The goal of gene therapy is to provide cells with the missing instructions they need to produce an important protein.
A good example is cystic fibrosis, a genetic disease caused by mutations in a single gene. Using DNA or an mRNA vaccine, researchers are investigating the possibility of essentially replacing the missing gene and enabling someone’s body to transiently produce the missing protein. Once the protein is present, the symptoms might go away, at least temporarily. The mRNA would not persist in the human body for very long, nor would it integrate into people’s genomes or alter the genome in any way. Additional doses would therefore be required as the effect wears off.
Research has shown that this concept is doable, but it still needs some work.
Written by Deborah Fuller, Professor of Microbiology, School of Medicine, University of Washington.
This article first appeared in The Conversation.