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New Vaccine Strategy May Mean The End Of The Line For Endless Boosters

Scientists at UC Riverside have demonstrated a new, RNA-based vaccine strategy that is effective against any strain of a virus and can be used safely even by babies or the immunocompromised.

Every year, researchers try to predict the four influenza strains that are most likely to be prevalent during the upcoming flu season. And every year, people line up to get their updated vaccine, hoping the researchers formulated the shot correctly.

The same is true of COVID vaccines, which have been reformulated to target sub-variants of the most prevalent strains circulating in the U.S.

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

"What I want to emphasize about this vaccine strategy is that it is broad," said UCR virologist and paper author Rong Hai. "It is broadly applicable to any number of viruses, broadly effective against any variant of a virus, and safe for a broad spectrum of people. This could be the universal vaccine that we have been looking for."

Traditionally, vaccines contain either a dead or modified, live version of a virus. The body's immune system recognizes a protein in the virus and mounts an immune response. This response produces T-cells that attack the virus and stop it from spreading. It also produces "memory" B-cells that train your immune system to protect you from future attacks.

The new vaccine also uses a live, modified version of a virus. However, it does not rely on the vaccinated body having this traditional immune response or immune active proteins—which is the reason it can be used by babies whose immune systems are underdeveloped, or people suffering from a disease that overtaxes their immune system. Instead, this relies on small, silencing RNA molecules.

"A host—a person, a mouse, anyone infected—will produce small interfering RNAs as an immune response to viral infection. These RNAi then knock down the virus," said Shouwei Ding, distinguished professor of microbiology at UCR, and lead paper author.

The reason viruses successfully cause disease is because they produce proteins that block a host's RNAi response. "If we make a mutant virus that cannot produce the protein to suppress our RNAi, we can weaken the virus. It can replicate to some level, but then loses the battle to the host RNAi response," Ding said. "A virus weakened in this way can be used as a vaccine for boosting our RNAi immune system."

When the researchers tested this strategy with a mouse virus called Nodamura, they did it with mutant mice lacking T and B cells. With one vaccine injection, they found the mice were protected from a lethal dose of the unmodified virus for at least 90 days. Note that some studies show nine mouse days are roughly equivalent to one human year.

There are few vaccines suitable for use in babies younger than six months old. However, even newborn mice produce small RNAi molecules, which is why the vaccine protected them as well. UC Riverside has now been issued a US patent on this RNAi vaccine technology.

In 2013, the same research team published a paper showing that flu infections also induce us to produce RNAi molecules. "That's why our next step is to use this same concept to generate a flu vaccine, so infants can be protected. If we are successful, they'll no longer have to depend on their mothers' antibodies," Ding said.

Their flu vaccine will also likely be delivered in the form of a spray, as many people have an aversion to needles. "Respiratory infections move through the nose, so a spray might be an easier delivery system," Hai said.

Additionally, the researchers say there is little chance of a virus mutating to avoid this vaccination strategy. "Viruses may mutate in regions not targeted by traditional vaccines. However, we are targeting their whole genome with thousands of small RNAs. They cannot escape this," Hai said.

Ultimately, the researchers believe they can 'cut and paste' this strategy to make a one-and-done vaccine for any number of viruses.

"There are several well-known human pathogens; dengue, SARS, COVID. They all have similar viral functions," Ding said. "This should be applicable to these viruses in an easy transfer of knowledge."

More information: Hai, Rong et al, Live-attenuated virus vaccine defective in RNAi suppression induces rapid protection in neonatal and adult mice lacking mature B and T cells, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2321170121. Doi.Org/10.1073/pnas.2321170121

Citation: New vaccine strategy may mean the end of the line for endless boosters (2024, April 15) retrieved 19 April 2024 from https://medicalxpress.Com/news/2024-04-vaccine-strategy-line-endless-boosters.Html

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Vaccine Breakthrough Could Mean Future-Proof Shots With No Need For Boosters

A new vaccine platform could see us waving goodbye to boosters for some diseases, as one shot could cover every possible future strain of a virus. So far, it's only been tested out in mice, but the scientists behind it are optimistic.

"This could be the universal vaccine that we have been looking for," said Rong Hai, a virologist at the University of California, Riverside, in a statement. 

The vaccine uses a live, attenuated version of the virus. Lots of existing vaccines, like the MMR and chickenpox vaccines, use a similar method. Unlike those, however, the new vaccines will not rely on the body's immune system mounting a response to the injected virus. Instead, they will activate a system called RNA interference, or RNAi.

It sounds a bit similar to the mRNA vaccines we've been using for COVID-19, but the way it works is quite different. 

"A host – a person, a mouse, anyone infected – will produce small interfering RNAs as an immune response to viral infection. These RNAi then knock down the virus," explained lead author Shouwei Ding, distinguished professor of microbiology. 

Viruses are generally able to get around this response by producing proteins that block the RNAi, but weakening the virus first overcomes this problem. "It can replicate to some level, but then loses the battle to the host RNAi response. A virus weakened in this way can be used as a vaccine for boosting our RNAi immune system," Ding said. 

And mutating won't save them either. "Viruses may mutate in regions not targeted by traditional vaccines. However, we are targeting their whole genome with thousands of small RNAs," Hai added. "They cannot escape this."

It's worth noting that the idea that RNAi can form part of humans' defense against viral infection has caused controversy, but that hasn't stopped a number of researchers beginning investigations into RNAi-based therapeutics over the last decade or so.  

The new vaccine platform also has one more big advantage. Because it doesn't rely on a traditional immune response from B and T cells, it could potentially be used in very young babies, or those with immune disorders who are normally ineligible for live vaccines. 

To test this, the researchers created a vaccine against a mouse virus called Nodamura. They gave a single injection to mice that had been genetically modified to remove their B and T immune cells. That one shot was enough to protect them from infection with Nodamura virus for at least three months – quite a long time, when you consider a mouse's typical lifespan of somewhere between two and three years.  

The vaccine worked even in newborn mice as they can already produce small RNAs, which is why it has potential for use in babies who would normally be too young to receive vaccines.

From their previous research, the team is convinced that flu infection also activates the RNAi system, so that's going to be their next target. They plan to develop a nasal spray vaccine, to avoid some of the issues and fears associated with needles. 

"Our next step is to use this same concept to generate a flu vaccine, so infants can be protected. If we are successful, they'll no longer have to depend on their mothers' antibodies," said Ding.

There's still some way to go, but if it is successful it's hoped that adapting the technology to cover other viruses would be relatively straightforward.

Ding explained, "There are several well-known human pathogens; dengue, SARS, COVID. They all have similar viral functions. This should be applicable to these viruses in an easy transfer of knowledge."

The study is published in the Proceedings of the National Academy of Sciences.

New 'One-And-Done' Vaccine Method Could Protect Infants—From Covid, Flu—With Just A Single Shot, Study Suggests

Topline

Researchers are pitching a new vaccine method for infants that offers continued protection with just a single dose, even if the virus mutates, according to a new study that could set the stage for "universal vaccines."

A patient getting vaccine.

Getty Images Key Facts

Vaccines for diseases like the flu are updated annually to accommodate for new variants, while vaccines for some diseases like COVID-19 are updated less frequently to target dominant variants of the virus circulating in the U.S.

There are different ways to create vaccines, but one of the most popular ways to make them is by including a weakened or inactive version of the virus, which in turn causes the body's immune system to produce T-cells that attack the virus and prevent it from spreading.

This new vaccine strategy—tested on mice—also uses a modified version of a virus, but instead of relying on the body's usual immune system response, it uses small interfering RNA molecules (siRNA), which stop the spread of disease, to create separate vaccines that target different diseases, according to a study published Monday in the Proceedings of the National Academy of Sciences.

Diseases thrive because they produce a protein that can block the production of siRNAs, but the new vaccine strategy creates and uses a mutant virus that can't produce these proteins, which allows the body's siRNAs to weaken the virus, regardless of if it mutates and makes a new variant.

The research team from the University of California, Riverside, believes because this strategy doesn't rely on the body's immune response to disease, it will also be suitable for babies, whose immune systems are still developing.

The researchers tested this method in baby mice and discovered they also produce siRNA, so they vaccinated them against a mouse disease called Nodamura, and they found the vaccine induced "rapid and complete protection" against the virus.

Crucial Quote

"It is broadly applicable to any number of viruses, broadly effective against any variant of a virus and safe for a broad spectrum of people," Rong Hai, a study author and virologist at the University of California, Riverside, said in a statement. "This could be the universal vaccine that we have been looking for."

Key Background

Though there are some approved vaccines for infants, vaccines for diseases like measles, COVID-19 and the flu can only be administered to people over the age of six months. This is because of their immature immune systems that cause a diminished response to these vaccines, and a potential lack of effectiveness, according to a study published in Vaccine. However, this group of people is one of the most susceptible to severe infection. Infants younger than six months have the highest risk of being hospitalized due to flu infection, according to the Centers for Disease Control and Prevention. In order to protect this population from infection, it's recommended that all household members and people who come into close contact with them get vaccinated from these diseases. Some research shows vaccinated mothers may pass antibodies to fetuses through the umbilical cord, and newborns via breast milk that can continue to protect the babies from infection. Respiratory syncytial virus (RSV) vaccines given to pregnant mothers have proven to protect infants up to six months after birth, according to the CDC.

Tangent

Though there aren't any approved siRNA vaccines, researchers are working on ones that target COVID-19 and the flu. It was previously debated whether humans and other mammals use interfering RNA to kill viruses. However, the same team from the University of California, Riverside also conducted research in 2013 that discovered this theory was true. The team later went on to prove flu infection causes the body to produce interfering RNA, so they're in the process of developing a flu vaccine that uses this strategy.

Surprising Fact

The researchers intend on creating this vaccine as a nasal spray rather than a shot. "Respiratory infections move through the nose, so a spray might be an easier delivery system," Hai said. There's already an approved nasal spray flu vaccine that's shown to be as effective in children as flu shots, according to the CDC. Several research teams are working on nasal COVID-19 vaccines, and both China and India have approved the use of nasal sprays in the form of boosters.

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