This is one of the greatest pandemic success stories: The unproven technology delivered the Moderna/Pfizer/BioNTech vaccines in record-breaking time. It helped to reverse the tide against Covid-19. The vaccines are made from mRNA, which is the molecule that instructs cells to produce specific proteins. Our cells can be made to produce synthetic mRNA by injecting it into them. This allows us to turn our cells into vaccine factories that make any protein we need for our immune system.
The technology was pre-pandemic and was considered a smart idea, but not certain that it would deliver. There is increasing confidence that mRNA vaccinations can be used to combat diseases such as flu and malaria.
Flu
Each February, flu researchers participate in an annual ritual. At a World Health Organization meeting, bets are made on which flu strains will prevail the next winter. There are currently four influenza viruses that are in circulation. Each virus is rapidly evolving, so the effectiveness of previous years' vaccines may be compromised. To produce vaccines, manufacturers need to wait at least six months. This is a tedious process that involves the cultivation of attenuated virus in millions of chicken eggs. While vaccines are 60% effective when the flu forecast is correct, vaccines may not be as effective if there is a mismatch between vaccines or circulating strains.
A universal vaccine that works across all four flu strains is the holy grail in flu research. It would also work for future generations as their genomes change over time. A vaccine that targets the core influenza protein would be necessary. This doesn't change from strain to strain. This part of the virus is not well-received by our immune systems, so this goal has been elusive for decades. Because mRNA is so easy to make, vaccines can be made to target multiple sites at once. Norbert Pardi from the University of Pennsylvania, a microbiologist, stated that such a vaccine is likely to trigger broad protective responses. His team is currently working on a vaccine candidate, which will contain about 12 pieces of mRNA. It is intended to be effective against several flu strains. Human trials are expected to start in 2023 by the team.
Cancer
The HPV vaccine protects against most cervical cancers. It has already prevented thousands of cases each year. Scientists hope that mRNA vaccines will be used in the future to prevent cancer. This is because they teach the immune system to recognize mutations before they happen, a completely new method of treatment. Professor Herbert Kim Lyerly from Duke University, who studies cancer vaccine technology, stated that we were taking advantage of the genetic progression of cancer.
His team will trial an mRNA vaccination next year for patients with advanced breast cancer. These patients are often resistant to drugs due to mutations in certain genes. Another advantage to mRNA is its ability to hit multiple targets simultaneously in this case, which means that it can target a few potential mutations. Lyerly stated that there is no better doctor than the immune system to identify [mutated cells] early in life.
If successful, the first applications could prolong a patient's life by keeping them from getting cancer for longer. It may eventually be possible to prevent certain types of cancer in high-risk groups like heavy smokers. This is because a mutation called KRAS in the gene that causes up to 25% of all cancers.
Malaria
The WHO approved the first rollout for a malaria vaccine in October. There is still room for improvement with the RTS-S vaccine, which reduces severe malaria by 30%. The main problem is that the malaria parasite has developed a method of preventing immune memory. People are still susceptible to infection even after being vaccinated. The disease claims the lives of 500,000 people each year, most of them children and babies.
Professor Richard Bucala of Yale School of Medicine and his colleagues discovered in 2012 that malaria could cause immune system amnesia by using a protein called PMIF. This protein kills memory T cells. Bucala is currently working on an RNA vaccine to immunise against PMIF.
Research in mice suggests that blocking the protein can make the immune system clear malaria faster, leading to milder symptoms and crucially, better immunity in the future. Bucala and scientists from Oxfords Jenner Vaccine Institute have teamed up to test the candidate. If positive, they plan to start human trials next year.
Bucala stated that vaccines for parasitic diseases are urgently needed in the developing world. Our PMIF vaccine has been a success thanks to RNA. RNA is also far cheaper than protein-based vaccines. This opens up new opportunities for a malaria vaccine.
HIV
Derek Cain of Duke University's Human Vaccine Institute said that we are now in the fifth decade of a global HIV pandemic. A vaccine is still not available.
The Cains team has concentrated on a small number of HIV patients (less than one-third), who develop antibodies that can kill HIV long after the infection. It is too late to eradicate the virus from the body by this point. Cain said that it is like finding a fire extinguisher, but the entire house is already on fire. These antibodies could be inducible by a vaccine, which could help to extinguish HIV before its spread.
Cain and his colleagues have carefully mapped the route the immune system takes to produce these highly specialized antibodies. They are now working together to concoct a series of four to five multi-targeted mRNA vaccines to recreate the arms race between pathogen and immune system.
Cain stated that we believe that the HIV vaccine will be the most complex vaccine we have ever put in the population. It is unlikely that it will work at 100% or 90% as the Covid vaccines. However, even if we could get to 50%-60% that would still be impressive. 70% would be incredible.
