Building a Universal Vaccine: The Potential of RNA Interference

Sunday - May 5 2024, 04:54 UTC - 6 months ago

Scientists are looking into new, innovative ways to create vaccines that can keep up with rapidly mutating viruses. One potential solution is using RNA interference, a natural immune response found in plants and invertebrates. This mechanism could potentially lead to a universal vaccine that can target all strains of a virus, including those that have mutated. While the potential is there, research is still ongoing and controversial. A team from UC California just designed a successful RNAi-based vaccine that protected mice from a deadly virus for at least 90 days.

From Covid boosters to annual flu shots, most of us are left wondering: Why so many, so often? There’s a reason to update vaccines. Viruses rapidly mutate, which can help them escape the body’s immune system, putting previously vaccinated people at risk of infection. Using AI modeling, scientists have increasingly been able to predict how viruses will evolve. But they mutate fast, and we’re still playing catch up.

An alternative strategy is to break the cycle with a universal vaccine that can train the body to recognize a virus despite mutation. Such a vaccine could eradicate new flu strains, even if the virus has transformed into nearly unrecognizable forms. The strategy could also finally bring a vaccine for the likes of HIV, which has so far notoriously evaded decades of efforts.

This month, a team from UC California Riverside, led by Dr. Shou-Wei Ding, designed a vaccine that unleashed a surprising component of the body’s immune system against invading viruses. In baby mice without functional immune cells to ward off infections, the vaccine defended against lethal doses of a deadly virus. The protection lasted at least 90 days after the initial shot.

The strategy relies on a controversial theory. Most plants and fungi have an innate defense against viruses that chops up their genetic material. Called RNA interference (RNAi), scientists have long debated whether the same mechanism exists in mammals—including humans.

"It’s an incredible system because it can be adapted to any virus," Dr. Olivier Voinnet at the Swiss Federal Institute of Technology, who championed the theory with Ding, told Nature in late 2013.

A Hidden RNA Universe .

RNA molecules are usually associated with the translation of genes into proteins.

But they’re not just biological messengers. A wide array of small RNA molecules roam our cells. Some shuttle protein components through the cell during the translation of DNA. Others change how DNA is expressed and may even act as a method of inheritance.

But fundamental to immunity are small interfering RNA molecules, or siRNAs. In plants and invertebrates, these molecules are vicious defenders against viral attacks. To replicate, viruses need to hijack the host cell’s machinery to copy their genetic material—often, it’s RNA. The invaded cells recognize the foreign genetic material and automatically launch an attack.

During this attack, called RNA interference, the cell chops the invading viruses’ RNA genome into tiny chunks–siRNA. The cell then spews these viral siRNA molecules into the body to alert the immune system. The molecules also directly grab onto the invading viruses’ genome, blocking it from replicating.

Here’s the kicker: Vaccines based on antibodies usually target one or two locations on a virus, making them vulnerable to mutation should those locations change their makeup. RNA interference generates thousands of siRNA molecules that cover the entire genome—even if one part of a virus mutates, the rest is still vulnerable to the attack.

This powerful defense system could launch a new generation of vaccines. There’s just one problem. While it’s been observed in plants and flies, where is it in mammals?Research in this field is still in its infancy and the findings are controversial.

As we await the results from ongoing clinical trials, Dr. Ding’s RNAi-based vaccine is once again showing out against several forms of the deadly virus in a new animal model.