UC Riverside Scientists Unveil RNA-based Vaccine Strategy, Potentially Avoiding Endless Booster Shots

Scientists at the University of California, Riverside (UC Riverside) have recently unveiled a groundbreaking RNA-based vaccine strategy that could revolutionize vaccination efforts against a myriad of viruses. Published in the Proceedings of the National Academy of Sciences (PNAS), their research introduces a vaccine design that not only promises effectiveness against various viral strains but also ensures safety, even for the most vulnerable populations like infants and the immunocompromised. More importantly, this novel strategy could lead to the development of a one-and-done vaccine for multiple viruses of concern such as dengue, influenza, SARS and COVID-19, potentially freeing people from receiving endless booster shots against various viral strains.

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A Promising Universal Vaccine Solution to Ever-Evolving Viruses

Conventional vaccines against viruses target particular viral strains, thus researchers and vaccine developers need to closely monitor the trend of viral evolution, predicting prevalent strains from time to time and formulating specific vaccines against them. For instance, in the case of influenza, vaccine manufacturers produce trivalent or quadrivalent vaccines following the World Health Organization’s recommendations on three to four viral strains most likely to be prevalent in the next flu season (two for influenza A plus one or two for influenza B). People therefore need to go to healthcare facilities every year to receive vaccination in the hope that the shot provide actual protection. Similarly, for COVID-19, researchers need to constantly reformulate vaccines in response to the emergence of new variant strains, and the public will inevitably need to receive booster shots for better protection.

Traditional vaccines rely on the host’s recognition of viral proteins to trigger immune responses, in which developers constantly face the struggle of keeping pace with the mutating nature of viruses. This time, the novel strategy of the UC Riverside team takes a different path, targeting a common fundamental part of the viral genome shared among all strains, opening up a possibility for a universal defense mechanism against different viruses, eliminating the need for annual flu shots and recurrent COVID-19 boosters. Dr. Rong Hai, UC Riverside’s Associate Professor of Virology and one of the two corresponding authors of the PNAS paper, commented on their discovery, “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.”

Harnessing RNA for Broad Spectrum Immunity Against Viruses

UC Riverside’s researchers utilized an RNA interference (RNAi)-based approach, harnessing small interfering RNA molecules (siRNA) to elicit immunity against viruses. These small double-stranded RNA molecules, usually 20–25 nucleotides in length, are produced naturally by the body in response to viral infections. They play an important role in silencing viral genes, thereby impeding viral replication and spread.

According to Dr. Shou-Wei Ding, UC Riverside’s Distinguished Professor of Microbiology and Plant Pathology and another corresponding author of the paper, their new approach bases on the fact that viruses cause disease in infected hosts by producing proteins that block their RNAi immune response (called viral RNAi suppressor, or VSR in short). By making a mutant virus which is unable to produce VSR, the virus can be attenuated. “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,” said Prof. Ding. 

Effective and Lasting Protection Demonstrated in Mice Model

In their study, UC Riverside researchers examined the protective antiviral immunity induced by immunization with a live-attenuated VSR-disabled RNA virus vaccine in laboratory mice, in an attempt to protect them against Nodamura virus (NoV). This mosquito-transmitted virus is highly virulent to suckling mice, leading to paralysis of limbs and eventually death. 

The team administered the vaccine in adult and neonatal mutant mice lacking mature B and T cells, the key components of the adaptive immune system. Remarkably, they found that a single vaccine injection could already provide full protection against a lethal dose of NoV and the effect persisted for at least 90 days post-vaccination, showcasing its potency in protecting individuals with compromised immune systems against viral challenges and its durability of action. Given the estimation from some studies that one human year is equivalent to nine mice days, this discovery could inspire the future development of long-acting vaccines for humans. The researchers also reported that the new vaccine exhibited similar promising results in protecting neonatal mice, suggesting its suitability for early-life vaccination in newborn babies, whose immune systems remain underdeveloped.

The Paradigm Shift: Toward One-and-Done Vaccination

With a US patent secured, UC Riverside researchers are optimistic about the vaccine’s potential. They envision a future where vaccine developers may apply this RNA-based strategy to a wide range of viruses beyond the mouse model, including well-known human pathogens like influenza, dengue, SARS and SARS-CoV-2 (COVID-19). By targeting the entire viral genome with thousands of small RNAs, the novel RNAi vaccine presents a formidable challenge which viruses stand almost no chance to escape.

Apart from pursuing the development of a single-dose “universal vaccine” which could provide long-lasting immunity against multiple viruses, the team is also exploring alternative delivery methods like nasal sprays, suiting the needs of those having an aversion to needles. Overall, this breakthrough study not only offers the hope for a paradigm shift in vaccination practices, but also opens the door to ending the cycle of annual vaccinations, freeing people from the trouble of receiving endless booster shots. 

Author

Richard Chau