The new type of vaccine does not focus on the production of antibodies and will therefore be suitable for both babies and people with a weakened immune system, the researchers promise. It can also put an end to the endless ‘boosting’.
We mainly know the ‘boosters’ from the time of the corona vaccinations. All mutations of the coronavirus were closely monitored and the vaccines were repeatedly adjusted accordingly. But people also queue up for the flu shot every year to protect themselves against the latest variant of the virus. Researchers at the University of California want to put an end to these repeated injections. They have developed a new strategy that should make adapted vaccines for new variants unnecessary.
Babies
This new vaccination strategy does not focus on a few specific properties of the virus, but on all parts of the viral genome (the entire genetic information of an organism). In addition, the vaccine is not dependent on the traditional human immune system response. This means that it may also be suitable for babies with an underdeveloped immune system, and for people who suffer from an illness that weakens their immune system.
What makes this vaccine different?
“The protective effect of current vaccines depends on our adaptive immunity, such as antibodies,” explains researcher Shou-wei Ding. In other words, from our ‘acquired immune system’ that arises from knowledge acquired from previous infections. For example, our immune system produces memory cells the first time we encounter a virus, so that it is better prepared the next time and an immune response is initiated more quickly. This principle is also used in vaccines, where the basis is often a weakened virus, part of it or an imitation of the virus. The vaccine of the UC Riverside focuses on another aspect of our immune system: the small molecules that cause ‘RNA interference’ (RNAi) after infection.
“We focus on the entire genome”
How does it work?
RNAi is a biological process that specifically targets defective proteins that cause disease. The process was previously mainly known in invertebrates, fungi and plants that do not have an immune system like us, but rely on this RNAi system for their defense. This system ensures that RNAi molecules attach to certain genes so that they can no longer make defective proteins, or to viral RNA, which they then attack and destroy. Because humans also have such an RNAi defense, the researchers thought that this route could also be a target for vaccines.
Mutations don’t matter
The big advantage of using this RNAi defense is that such a vaccine can protect against a much larger group of viruses, says colleague Rong Hai. “Viruses can mutate in regions not targeted by traditional vaccines. In contrast, we focus on the entire genome with thousands of small RNAs. She (ed. the viruses) so we cannot escape this.” This applies even to the most difficult to reach regions, such as the ends of the viral genome (the 3′ and 5′ ends), Ding adds. “This makes it possible to recognize almost all strains of a certain virus family.”
Mutant virus as a vaccine
The principle of the vaccine is based on existing RNAi therapies, says Ding. “These therapies inhibit specific gene expressions by delivering chemically synthesized small interfering RNAs (siRNAs).” By using this principle to create a vaccine, it is possible to induce the natural production of a large population of siRNAs, Ding said. The vaccine itself therefore consists of a modified variant of a virus. Normal viruses can produce proteins that block the host’s release of RNAi molecules, but the modified virus cannot do this. The virus can reproduce to a certain extent, but will eventually lose the battle. This way the body has enough time to train the RNAi defense.
Animal testing
Researchers confirmed this after they tested this technique by infecting mutant mice with mouse virus Nodamura. The mice lacked T and B cells (important players in the immune system) and were therefore poorly protected against infections. The mice that received one RNAi vaccine injection subsequently appeared to be protected against a lethal dose of the real virus. In any case, for at least ninety days, which must be approximately equivalent to ten years in a human life.
“If this is successful, newborns will no longer have to rely on their mothers’ antibodies.”
Solution for humans?
Although it is a good result, universal vaccines will have to wait a while, says Ding. “We must first find out whether we can reproduce the result with one or more human viral pathogens in at least one animal model before attracting partners and funding to prepare clinical trials. In that regard, it is difficult for us to predict when we will have a vaccine product available to the public.” UC Riverside has already received an American patent on this RNAi vaccine technology.
Vaccines in spray form
Should the technology produce approved vaccines, that will be good news for people with weakened immune systems and babies. Where the adaptive immune system develops over the years, even newborn mice can already produce RNAi molecules. Which explains why the vaccine also protected them. The first step is to make a flu vaccine with this technique. “If this is successful, newborns will no longer have to depend on their mothers’ antibodies,” says Ding. To make it even more user-friendly, these vaccines could probably also be delivered in the form of a spray, as is currently the case with some flu vaccines.
It will therefore take some time before an RNAi vaccine is on the market, but the researchers are hopeful. Ding: “We have demonstrated long-term protection in mutant mouse strains without a functional adaptive immune system. We now have to wait and see whether this is reproducible in humans.”
Universal flu shot
For most people, flu is just a kind of bad cold. But the elderly and vulnerable can suffer serious complaints and even die from it. Because the flu virus mutates very quickly, a new vaccine is developed every year. Although the jab provides protection, it remains a so-called ‘seasonal vaccine’ and only provides protection against recently circulating strains. A universal flu vaccine has been sought for some time now. Such as the mRNA vaccine from the Perelman School of Medicine at the University of Pennsylvania. This universal flu vaccine in development was tested to provide protection against all twenty known subtypes of the flu virus. The universal vaccine has yet to be tested on humans.
Tags: vaccine technology protects multiple virus variants work newborns
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