Vaccine breakthrough means there's no need to chase stocks anymore

Every year, researchers try to predict the four influenza strains that are most likely to circulate during the upcoming flu season. And every year, people line up to get the latest vaccine, hoping that researchers got it right.

The same is true of coronavirus vaccines, which have been reformulated to target subvariants of the most prevalent strains circulating in the United States.

This new strategy targets a part of the viral genome that is common to all strains of the virus, eliminating the need to make all these different shots. The vaccine, how it works, and the demonstration of its effectiveness in mice are described in a paper published today. Proceedings of the National Academy of Sciences.

“What I want to emphasize about this vaccine strategy is that it's broad,” said Ron Haigh, a UCR virologist and study author. “It's broadly applicable to any number of viruses, broadly effective against all variants of the virus, and safe for a wide range of people. This could be the universal vaccine we've been looking for.” ”

Traditionally, vaccines contain killed or modified live viruses. The body's immune system recognizes the proteins within the virus and mounts an immune response. This reaction produces T cells that attack the virus and stop it from spreading. It also produces “memory” B cells that train the immune system to protect against future attacks.

The new vaccine also uses a live, modified virus. However, this vaccine does not rely on the vaccinated body having this traditional immune response or immune active proteins. This is why it can also be used in infants with underdeveloped immune systems and people suffering from illnesses that overburden the immune system. Instead, it relies on small RNA molecules that perform the silencing.

“The host, whether it's a human, a mouse, or anyone who's infected, produces small interfering RNAs as an immune response to viral infection. And these RNAi knock down the virus,” says UCR's distinguished microbiology professor. said Mr. Shuwei Ding, a professor and author of the paper.

The reason viruses can cause disease is because they produce proteins that block the host's RNAi response. “If we create a mutant virus that cannot produce proteins that suppress RNAi, we can weaken the virus. It can replicate up to a certain level, but after that it loses the battle against the host's RNAi response,” Ding said. Ta. “Viruses weakened in this way can be used as vaccines to boost the RNAi immune system.”

When the researchers tested this strategy with a mouse virus called Nodamura, it also worked in mutant mice lacking T and B cells. They found that a single injection of the vaccine protected mice from a lethal dose of the unmodified virus for at least 90 days. Note that some studies have shown that a mouse's 9 days is roughly equivalent to a human's 1 year.

Few vaccines are suitable for use in infants younger than 6 months of age. But newborn mice also produce small RNAi molecules, so the vaccine also protected them. The University of California, Riverside has been awarded a US patent for his RNAi vaccine technology.

In 2013, the same research team published a paper showing that influenza infection also induces the production of RNAi molecules. “So our next step is to utilize this same concept to produce a flu vaccine so that it can protect infants. If we are successful, infants will develop their mother's antibodies. We no longer have to rely on it,” Ding said.

The company's flu vaccine will also likely come in spray form, as many people dislike needles. “Respiratory infections are transmitted through the nose, so the spray may be easier to spread,” High said.

Additionally, researchers say there is little chance of the virus mutating to evade this vaccination strategy. “Viruses can mutate in regions not targeted by traditional vaccines. But we target the entire genome of the virus with thousands of small RNAs. The virus can't escape this. '' said Mr. High.

Ultimately, researchers believe this strategy could be “cut and pasted” to create a one-time vaccine for any number of viruses.

“There are several well-known human pathogens, such as dengue fever, SARS, and the novel coronavirus. They all have similar viral functions,” Ding said. “This should be applicable to these viruses by easily transferring knowledge.”