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The flu vaccine changes every year, and the new crown vaccine often receives two or three shots, which is not enough to get a booster shot. A common impression of vaccines is that they are available in many types and are updated quickly.
The reason for the high frequency of vaccine updates is that the virus can mutate quickly, thus gaining the ability to evade specific immunizations, making the original effective vaccination ineffective and putting the body at risk of infection again. With the help of artificial intelligence, scientists are constantly improving their understanding and prediction of the evolution of the virus. But for now, the virus is still evolving far ahead of scientific predictions.
The so-called universal vaccine refers to a vaccine that can target the new strain formed by the virus mutation and can be effective for a long time after vaccination. It is a beautiful dream of mankind to "take care of it forever", and it is also a new strategy for the prevention of infectious diseases that is being brewed in the academic community, and it is expected to bring vaccines against AIDS and other diseases in the future.
Recently, the team of microbiologist Ding Shouwei at the University of California, Riverside, reported its latest results in the Proceedings of the National Academy of Sciences (PNAS): a prototype of a universal viral vaccine that helps release long-term "dormant" components in the human immune system to fight various invaders.
They gave the vaccine to young rats that had no functional immune cells and struggled to defend themselves against infection, only to miraculously withstand a lethal dose of the deadly virus, with the initial vaccination lasting protection for at least 90 days.
Prof. Ding's team's universal vaccine strategy is based on the controversial theory that most plants and fungi have an innate defense against viruses that destroy their genetic material (undisputed), and that mammals, including humans, may have a similar defense mechanism, namely RNA interference (RNAi), which helps the body fight off various invaders (long-standing controversy).
Dr. Olivier Voinnet, a scholar at the Swiss Federal Institute of Technology, shares the same view as Professor Ding. In a 2013 interview with the journal Nature, he said, "It's an incredible system because it adapts to any virus. ”
Hidden RNA interferes with the world
We all know that RNA molecules are involved in the process of expressing genetic information, but they are more than just biological messengers. There is a so-called small interfering RNA (siRNA) molecule that is a powerful force against viral infection.
In plants and invertebrates, when a virus invades, the host cell usually automatically recognizes the foreign genetic material (the virus needs to hijack the host cell to copy its own genetic material, usually RNA) and strikes the enemy hard. This set of punches is the RNA interference mentioned earlier:
The host cell cuts the RNA genome of the invading virus into small pieces, known as siRNAs, and then delivers these molecules into the body to warn the immune system.
What's more, the siRNA molecules originating from the virus can capture the virus's own genome and prevent it from replicating! More importantly, a large number of siRNA molecules produced by the RNA interference process can suppress the entire viral genome in all directions - even if one part of the virus mutates, the rest is still the target.
At the heart of traditional vaccines are antibodies, which usually target one or two parts of the viral genome and are therefore easily ineffective due to viral mutations. Scientists see RNA interference as the cornerstone of a new generation of vaccines. However, there is a key question that arises: as mentioned earlier, the question of whether there is an RNA interference mechanism in mammals has always been controversial.
In a 2013 interview with the journal Nature, Ding Shouwei said: "We believe that the antiviral effect of RNA interference has been around for hundreds of millions of years. Why should we mammals give up such effective defenses?"
Born a virus killer
In 2013, Ding and colleagues wrote in the journal Science that mammals also have an RNA interference mechanism that produces large amounts of siRNA, but most viruses carry specific genes that inhibit siRNA production.
This gene, known as B2, inhibits all possible RNA interference responses by disrupting the host cell's ability to make siRNA fragments.
So, when a virus loses its B2 gene, is it unable to inhibit RNA interference?
Professor Ding et al. genetically modified a virus lacking the functional B2 gene and used it to infect hamster cells and immunocompromised mouse pups. The virus, known as the Nodamura virus, is transmitted by mosquitoes in the wild and is usually fatal. But after losing B2, even a lethal dose of the Nodamura virus is not lethal. Mouse pups can rapidly produce large amounts of siRNA molecules to eliminate invaders from viral infection.
Vaccines for the new era
Many traditional vaccines contain inactivated or attenuated viruses designed to train the body's immune system. When the vaccinated person is confronted with the real virus, the body can produce T cells that hit the target directly, B cells that make antibodies, and immune memory cells that take precautions. But their effects are not long-lasting, especially when the virus mutates.
These viruses could be formulated into a new type of vaccine, which the team has been working on to develop that relies on RNA interference to ward off invaders. Theoretically, the large number of siRNA molecules triggered by the vaccine could also provide some protection against future infections. Ding Shouwei's team has been committed to the research and development of new vaccines for a long time, and its basic ideas are:
The B2 gene of the virus is deleted so that it is unable to make proteins that inhibit RNA interference, and then used to induce the body to produce large amounts of siRNAs, which will provide comprehensive and long-lasting protection for the vaccinated.
In the new PNAS study, the authors' team gave a single injection of Nodamura virus in both juvenile and adult mice, which lost the B2 gene. These mice are genetically modified to have impaired immune function and are unable to initiate T-cell or B-cell defenses. Two days after vaccination, a lethal dose of normal virus was administered, and the mice were unharmed. The immune protection lasted for more than three months.
Pre-stocking large amounts of siRNA may be an ideal alternative strategy for infants, the elderly, and other immunocompromised individuals who may not be well protected by conventional vaccines due to their weakened autoimmunity.
On the other hand, scientists have found the B2 protein in many common viruses, including dengue fever, flu, and the family of viruses that cause fever, rash, and blisters.
Ding's team is developing a new influenza vaccine based on live B2 protein-free virus, which is expected to be administered in the form of a nasal spray. If this siRNA theory is true, the new vaccine will be able to cope with various mutant strains.
Sources:
A Universal Vaccine Against Any Viral Variant? A New Study Suggests It’s Possible
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