Health and Medicine
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In what could be considered a revolutionary breakthrough, scientists have created a “universal” vaccine formula that protects mice against a suite of respiratory viruses, bacteria, and even allergens. It’s delivered as a nasal drop, so no needles, and produces stable protection – and it does all this in a way that no vaccine has ever worked before.
A totally new approach
All traditional vaccines work by priming the immune system to respond quickly to specific pathogens. Sometimes we combine several in one shot, like the MMR vaccine – but that still only protects you against measles, mumps, and rubella.
We’ve also found lots of different ways of doing this, from the very early days of Edward Jenner rubbing cowpox on people, to modern mRNA vaccines against SARS-CoV-2 spike proteins. But the basic principle is the same.
“That’s been the paradigm of vaccinology for the last 230 years,” said senior author and professor of microbiology and immunology Bali Pulendran in a statement.
For some diseases, this approach is perfectly effective. To use the earlier example of the MMR, two doses of that will give you extremely high levels of protection against those viruses that can persist for most of your life. However, some viruses are trickier customers. Flu viruses and SARS-CoV-2 have a tendency to mutate and produce new variants, which older vaccines aren’t as effective against. That’s why we need boosters for these viruses much more regularly.
“Like the proverbial leopard that changes its spots, a virus can change the antigens on its surface,” said Pulendran. Clearly, for these viruses, a different proposition is needed.
The idea of “universal” or broadly protective vaccines isn't new. It has been observed that some people immunized with the BCG vaccine for tuberculosis (TB) or the oral polio vaccine have some off-target protection against other, unrelated pathogens.
IFLScience previously chatted with vaccinologist Professor Florian Krammer on an episode of The Big Questions, in which we discussed the challenges associated with creating a universal flu vaccine.
For that, we were only talking about a hypothetical shot that could protect you against any type of flu virus, even ones that haven’t been seen before in humans. But Pulendran and the team behind the new study have take a massive step further – further, even, than they dared hope.
“We were interested in this idea because it sounded a bit outrageous. I think nobody was seriously entertaining that something like this could ever be possible,” said Pulendran.
The vaccine platform they created doesn’t focus on a particular pathogen at all. Instead, it contains molecules that can bind to and activate receptors in the body that are part of the immune system’s internal communication network. It also contains a harmless antigen called ovalbumin, a protein found in eggs. In a traditional vaccine, the antigen would be a piece of the pathogen you’re trying to immunize against.
The effect of these two elements together is to activate both the innate and adaptive immune systems.
Innate immunity kicks into gear very quickly after exposure to an infectious agent, producing a rapid but less specific response. This wanes after a few days, once the adaptive immune system – which includes the cells that can produce specific antibodies – has had a chance to mount a response more tailored to the specific pathogen you are fighting off.
Traditional vaccines rely on this adaptive immune response. That’s why it usually takes a couple of weeks to get full protection – you’re waiting for those specific antibodies to build up.
But the innate immune system could be a powerful weapon too, if only we could figure out how to wield it.
“What’s remarkable about the innate system is that it can protect against a broad range of different microbes,” said Pulendran.
In 2023, Pulendran and a team of colleagues published a study that showed the first hints of an answer. They figured out that the reason the BCG vaccine is able to confer protection against diseases other than TB is that it can produce both innate and adaptive immune responses that last.
Unusually, the T cells recruited as part of the adaptive immune response keep the innate immune response on life support, long after it would usually have waned.
As long as this was the case, the team observed, mice given the BCG vaccine were also protected against COVID-19. Based on this, they hypothesized that they could create a synthetic vaccine that works through a similar mechanism.
“Fast forward two and a half years,” Pulendran said, “and we’ve shown that exactly what we had speculated is feasible in mice.”
Viruses, bacteria, and allergens (oh my)
The experimental vaccine, called GLA-3M-052-LS+OVA, was given as a droplet via the nose to groups of mice – they got up to four doses, with a week in between each. A future human vaccine could take the form of a nasal spray.
After allowing the vaccine to take effect, the mice were challenged by exposure to different respiratory viruses. Three doses of the vaccine were enough to protect them against coronaviruses, including SARS-CoV-2 and ones that cause the common cold, for at least three months.
The protection is fortified in the lungs, which is great for respiratory pathogens as this is where they typically first enter the body. With a strong innate response, Pulendran explained, they saw levels of virus in the lungs decreased 700-fold. Any that slip through the net can be mopped up by the adaptive response.
Seeing the incredible results in viruses, the team essentially asked themselves, “What can’t this vaccine handle?” And the answer is, not much! The mice were also found to be protected against two bacterial pathogens, Staphylococcus aureus and Acinetobacter baumannii. They even tested the response to a common allergy trigger, a protein from dust mites. The vaccinated mice showed no allergic response.
“I think what we have is a universal vaccine against diverse respiratory threats,” said Pulendran.
The process of translating animal model findings to human medicine is long, slow, and prone to failure. As exciting as this all is, it will be at least five to seven years, in Pulendran’s estimation, before we could see such a vaccine for use in humans, and that’s a best-case scenario.
But if all goes well, it could be truly transformative. Imagine one nasal spray that covers you against COVID, flu, the common cold, bacterial infections, and household allergens, for several months at a time.
We’ll be keeping our fingers crossed for this one.
The study is published in Science.
