Each year, researchers try to predict the four strains of influenza most likely to circulate during the next flu season, and people go to get vaccinated in the hope that the chosen formulation is the right one. This process also applies to COVID vaccines, which are continually adapted to address the prevailing subvariants at any given time.
Now, scientists at the University of California, Riverside have developed an innovative RNA-based vaccination strategy that appears to be effective against any variant of a virus, and is safe even for infants or people with compromised immune systems.
This new strategy eliminates the need to generate different types of vaccines, as it focuses on a part of the viral genome that is common to all strains of a virus. The vaccine, its mechanism of action and its effectiveness in mice are detailed in an article that has been published in the Proceedings of the National Academy of Sciences (PNAS).
“What I want to emphasize about this vaccination strategy is that it is broad,” said UCR virologist and author of the article, Rong Hai. “It is widely applicable to any number of viruses, widely effective against any variant of a virus and safe for a wide spectrum of people. “This could be the universal vaccine we were looking for.”
Traditionally, vaccines contain inactivated or modified live versions of a virus. The immune system recognizes a protein from the virus and initiates an immune response that generates T cells, which attack the virus, preventing its spread, and memory B cells that prepare the immune system for future attacks.
The new vaccine also uses a modified, live version of the virus, but does not rely on the traditional immune response or active immune proteins, allowing it to be used in babies with developing immune systems or in people with diseases that weaken their immunity. Instead, it relies on small, silencing RNA molecules. “A host – a person, a mouse, any infected individual… – will produce small interfering RNA as an immune response to the viral infection. These RNAi then destroy the virus,” said Shouwei Ding, distinguished professor of microbiology at UCR and senior author of the study.
Create a single and definitive vaccine for numerous viruses
Viruses can cause disease because they produce proteins that block the host’s RNAi response. “If we create a mutant virus that cannot produce the protein to suppress our RNAi, we can weaken the virus. It can replicate to a certain level, but then loses the battle to the host’s RNAi response,” Ding said. “A virus weakened in this way can be used as a vaccine to stimulate our RNAi immune system.”
Testing this strategy with a mouse virus called Nodamura in mutant mice lacking T and B cells, the researchers found that a single injection of the vaccine protected the mice from a lethal dose of the unmodified virus for at least 90 days. It is important to mention that some studies indicate that 9 days in mice is approximately equivalent to a human year.
“Viruses can mutate in regions where traditional vaccines are not targeted. However, we target your entire genome with thousands of small RNAs. “They can’t escape this.”
There are few vaccines suitable for babies under six months. However, even newborn mice produce small RNAi molecules, which explains the protection conferred by the vaccine. The University of California, Riverside has obtained a US patent for this RNAi vaccine technology.
In 2013, the same research team showed that influenza infections also induce us to produce RNAi molecules. “So our next step is to use this same concept to generate a flu vaccine so that babies can be protected. If we are successful, they will no longer have to rely on their mothers’ antibodies,” adds Ding.
This flu vaccine will likely be given as a spray, since many people prefer to avoid needles. “Respiratory infections are transmitted through the nose, so a spray might be an easier delivery system,” Hai said.
Furthermore, researchers consider that there is little chance that viruses will mutate to evade this vaccination strategy. “Viruses can mutate in regions where traditional vaccines are not targeted. However, we target your entire genome with thousands of small RNAs. “They can’t escape this,” Hai explained.
Eventually, researchers believe they can adapt this strategy to create a single, definitive vaccine for numerous viruses. “There are several well-known human pathogens; dengue, SARS, COVID. “They all have similar viral functions.” “This should be applicable to these viruses in easy knowledge transfer,” Ding concluded.
