Unproven technology delivered the Moderna and Pfizer/BioNTech vaccines in quick time, helping to turn the tide on Covid-19. mRNA is the molecule that tells our cells to generate specific proteins. By introducing synthetic mRNA into our cells, we may train our immune system to recognise and destroy any protein we wish.

Prior to the outbreak, the technology was viewed with scepticism — it was a great concept, but it wasn’t guaranteed to work. There is now a growing belief that mRNA vaccines could have far-reaching uses in diseases ranging from influenza to malaria.

Vaccine for Flu

Every February, flu experts gather at the World Health Organization to put bets on which flu viruses will dominate the next winter. There are four influenza viruses circulating, each quickly changing, reducing vaccine efficacy. Vaccine production takes six months and includes producing attenuated virus in millions of chicken eggs. Vaccine efficacy might range from 60% to 10% depending on the flu forecast.

The goal of flu research is to develop a universal vaccine that will protect against all four types as their genomes shuffle over time. A vaccine targeting the core influenza protein would be required. Sadly, our immune systems do not respond well to this viral component. However, because mRNA is so quick and inexpensive to create, vaccines can be engineered to attack multiple locations at the same time.

“Such a vaccine will likely be able to induce broadly protective responses,” microbiologist Norbert Pardi from the University of Pennsylvania said, who is already working with his team on a vaccine candidate that will use about a dozen pieces of mRNA and is designed to work across several flu strains. The team hopes to begin human trials in 2023.

Treatment for Cancer

Thousands of cases of cancer are prevented each year thanks to the HPV vaccine, which protects against the virus that causes most cervical malignancies. In the future, scientists plan to utilize mRNA vaccines to prevent cancer by educating the immune system to recognize mutations before they occur, which would be a completely new strategy to treatment.

“We’re taking advantage of the known genetic progression of cancer,” Prof Herbert Kim Lyerly from Duke University said.

His team wants to test an mRNA vaccine in advanced-stage cancer patients next year, when tumors frequently develop drug resistance due to alterations in certain genes. Again, mRNA has the advantage of being able to attack numerous targets at once — in this example, a small number of possible alterations.

“There’s no better surgeon in the world than your immune system to pick off those [mutated cells] in the early stage,” said Lyerly.

If effective, the first applications could add months to a patient’s life by keeping cancer at bay for longer. It may eventually be feasible to prevent cancer in certain high-risk populations, such as heavy smokers, where a mutation in the KRAS gene is responsible for up to a quarter of all malignancies.

Malaria vaccine

The World Health Organization (WHO) approved the first malaria vaccine rollout in October. However, with the RTS,S vaccine lowering severe malaria by 30%, there remains room for improvement. The malaria parasite has evolved a method of preventing immunologic memory, which poses a significant obstacle. People are prone to re-infection even after being vaccinated against malaria, and the disease kills 500,000 people each year, largely babies and children.

Prof. Richard Bucala of Yale School of Medicine and colleagues found in 2012 that malaria causes “immune system amnesia” by killing memory T-cells utilizing a protein called PMIF. Bucala is developing an RNA vaccine that will protect against PMIF.

Blocking the protein, according to mouse studies, permits the immune system to eliminate malaria more quickly, resulting in a milder illness and, most importantly, future immunity. Bucala has teamed up with experts at Oxford’s Jenner Vaccine Institute to investigate the candidate, with the goal of starting human trials next year if the results are positive.

“Vaccines are desperately needed in the developing world for parasitic diseases that have long depressed economic and societal development of many countries,” said Bucala.

“RNA has not only enabled the success of our PMIF vaccine but the platform is far less expensive than protein-based vaccines, opening opportunities for a malaria vaccine that have not previously existed.”

HIV

“We’re going into the fifth decade now of a global pandemic for HIV,” said Derek Cain of Duke University’s Human Vaccine Institute. A vaccine has remained elusive so far.

Cain’s research has concentrated on a small percentage of HIV patients (less than one-third) who generate specialized antibodies that can neutralize HIV years after infection. There is a large reservoir of virus in the body by this point, and it is too late to cure the infection.

“It’s like you find a fire extinguisher but the whole house is on fire already,” said Cain.

However, if these antibodies could be induced by a vaccination, HIV may be eradicated before it spreads.

Cain and colleagues have methodically sketched out the immune system’s circuitous approach to producing these highly specialised antibodies, and as part of a collaboration, they are developing a series of four or five multi-target mRNA vaccines to “recreate the arms race between the immune system and the pathogen”.

“We certainly think that an HIV vaccine will be far and away the most complicated vaccine that we’ve ever had to put into the population,” said Cain.

“We don’t expect it to work 100% or 90% like the Covid vaccines, but even if we can get to 50-60% that would be a success; 70% would be amazing.”

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