A PNAS study shared by researchers at UC Riverside in April 2024 explores the benefits of a “one-and-done” approach to vaccinations for infectious diseases. The paper characterises a “unique live-attenuated RNA virus vaccine”, in which attenuation resulted from the elimination of the viral RNAi suppressor and enhanced the production of virus-targeting small-interfering RNAs. The researchers identify “potential for developing a distinct type of virus vaccine” to provide “rapid and effective protection” in “infants and other immune-compromised individuals”.
Investigating the vaccine
In the paper the authors present their investigations into the protective antiviral immunity induced in mice through immunisation with NoVΔB2. NoVΔB2 is a live-attenuated, VSR-disabled RNA virus vaccine. Previous studies have “extensively characterised” its RNA-based virus-specific antiviral responses. In this study, mice “produce highly abundant NoV (Nodamura virus)-specific vsiRNAs that are readily detectable”. These vsiRNAs have a role as the “specificity-determinants of the induced antiviral immunity”. Mice who had been immunised with NoVΔB2 also “specifically” suppressed the accumulation of a recombinant Sindbus virus carrying a NoV RNA sequence.
“Our findings from this work show that the protective antiviral immunity induced by a single shot with live NoVΔB2 is both virus-specific and long-lasting, which are the same as those virus vaccines that activate the adaptive immunity.”
However, the protective immunity induced in this study reveals “several distinct features”. After immunisation, neonatal BALB/c and Rag1−/− mice became “fully protected” against lethal NoV challenge and exhibited “no signs of diseases”. Furthermore, NoV accumulation was “undetectable in most or all” neonatal BALB/c and Rag1−/− mice following NoV inoculation. This reveals “efficient inhibition of the challenge infection” in newborn mice due to the induced antiviral responses”.
The results also indicate that the adaptive immunity mediated by B and T lymphocytes is “dispensable for the protective immunity activated by immunisation with the live-attenuated VSR-disabled NoVΔB2.”
“These distinct features of NoVΔB2-induced protection align with the earlier conclusion that enhanced production of the circulating and stably maintained virus-targeting vsiRNAs confers antiviral protection by the RNAi pathway in mice immunised with the live-attenuated VSR-disabled virus vaccine.”
Broad protection and other applications
A statement from UC Riverside considers the risks associated with predicting and targeting viral strains. This is exemplified in annual flu vaccine efforts.
“People line up to get their updated vaccine, hoping the researchers formulated the shot correctly.”
However, the latest evidence suggests that targeting a “common” part of the viral genome could “eliminate the need to create all these different shots”. Dr Rong Hai, one of the authors of the paper, emphasises that the strategy is “broad”.
“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.”
Distinguished professor of microbiology and lead paper author is Dr Shou-wei Ding, who is seeking to “weaken the virus” so that it “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.”
This research has particularly positive implications for infants, who would “no longer have to depend on their mothers’ antibodies” and could be used for “several well-known human pathogens” such as dengue and SARS.
“This should be applicable to these viruses in an easy transfer of knowledge.”
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