Could a Novel RNA-Based Vaccine Strategy Stop Endless Boosters?
A new vaccination strategy utilizing small interfering RNA could offer continued protection even if a virus mutates.
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Each year, seasonal influenza vaccines are designed to protect against the four main types of flu that researchers predict are likely to be most prevalent in the upcoming flu season. A decline in vaccine-specific antibodies in the body, the antigenic drift of influenza viruses over time and the emergence of novel strains of the virus result in this need for annual revaccination.
Now, a novel RNA-based vaccine strategy developed by scientists at the University of California, Riverside (UCR) may eliminate the need to chase new strains of viruses. The research is published in the Proceedings of the National Academy of Sciences.
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“Traditional vaccines depend on adaptive immunity such as antibodies to provide specific protection,” Shou-Wei Ding, distinguished professor of microbiology at UCR and lead paper author, told Technology Networks.
The new vaccine developed at UCR does not rely on the vaccinated body having a traditional immune response or immune active proteins. Instead, it relies on small interfering RNA molecules.
What are small interfering RNA (siRNA) molecules?
Small interfering RNA (siRNA), also known as silencing RNA, is a class of 20–25 nucleotide-long double-stranded RNA molecules most notably involved in the RNA interference (RNAi) pathway where they interfere with specific genes. In 2001, synthetic siRNAs were shown to be able to induce RNAi in mammalian cells, leading to an interest in harnessing RNAi for drug discovery.
“Our vaccine-induced inhibition of infection mechanistically resembles RNAi therapeutics, which inhibit specific gene expression by delivering chemically synthesized siRNAs. Our vaccines induce the natural production of a large population of siRNAs to target all viral RNAs for degradation. We have demonstrated full protection in mutant mouse strains without a functional adaptive immune system,” said Ding.
In the study, the scientists characterized a unique live-attenuated RNA virus vaccine, utilizing a mouse virus called Nodamura. Attenuation resulted from the elimination of the viral RNAi suppressor, enhancing the production of virus-targeting siRNAs.
The results showed that single-dose immunization with the vaccine just 2 days in advance induced full protection in neonatal and adult mutant mice lacking adaptive immunity. Moreover, the immunized mutant mice remained protected against lethal challenge for at least 90 days postvaccination.
Rapid and complete protection for children
This new type of vaccine strategy does not require the body to have traditional immune active proteins; during the study, even newborn mice produced small RNAi molecules. Therefore, the researchers suggest that this vaccination strategy could be used in babies with underdeveloped immune systems or individuals with a compromised immune system.
Summarizing the potential benefits of the new vaccine strategy, Ding said: “Protection is induced (i) much faster than traditional vaccines (2 days after vaccination instead of a week or longer); (ii) in young infants and adult patients with under-developed or compromised adaptive immunity; (iii) to completely prevent infection in most vaccinated individuals rather than only reducing disease severity.”
Combating the arrival of new strains
When a virus replicates, its genes undergo random genetic mutations. Over time, these mutations can lead to alterations in the virus’ surface proteins or antigens. In influenza viruses, genetic mutations accumulate and cause the antigens to drift. When the influenza virus drifts enough, vaccines against old strains of the virus and immunity from previous infections are no longer effective. Antigenic drift is one of the main reasons the flu vaccine must be reviewed and updated yearly.
The novel vaccine strategy developed by the researchers targets the entire viral genome with thousands of siRNAs. The researchers believe there is little chance of a virus mutating to avoid this vaccination strategy.
“Traditional vaccines induce strain-specific protection by recognizing a few regions of a viral surface antigen. Thousands of virus-targeting siRNAs are induced by our vaccines to recognize all regions of the viral RNAs, which should be able to recognize all or most strains of a virus,” said Ding.
Working towards a universal vaccine
An earlier study by the same research team identified that flu infections also induce the body to produce siRNAs. The scientists’ next step is to use this concept to generate a flu vaccine for infants, enabling them to no longer depend on their mothers’ antibodies for protection.
The researchers intend to create this vaccine as a nasal spray as opposed to an injection, recognizing that some individuals have an aversion to needles. This would not be the first nasal spray flu vaccination to be approved for use in children.
Several other well-known human pathogens such as dengue and COVID all have similar viral functions. The researchers believe this new vaccine strategy should apply to them all and could allow for the creation of a “one-and-done” vaccine for any number of viruses.
Ding concludes: “We aim to see if this also works in humans. Our work provides a new vaccination strategy, which may facilitate the development of vaccines against viruses without any vaccine available or vaccines that can prevent infection (not just reducing virulence).”
Prof. Shou-Wei Ding was speaking to Blake Forman, Senior Science Writer & Editor for Technology Networks.
About the interviewee:
Shou-Wei Ding is a distinguished professor of microbiology at UCR. He received his PhD from the Australian National University. His current research focuses on understanding the host immune response to RNA viruses and viral counter-defense strategies.
Reference: Chen G, Han Q, Li WX, Hai R, Ding SW. Live-attenuated virus vaccine defective in RNAi suppression induces rapid protection in neonatal and adult mice lacking mature B and T cells. PNAS. 2024;121(17):e2321170121. doi: 10.1073/pnas.2321170121
