For each pathogen, its vaccine. It’s a rule that has held true for over 200 years, since Jenner’s first pioneering experiments with the smallpox vaccine. But today there are those who are trying to undermine this paradigm, to obtain a vaccine capable of protecting against any respiratory infection – no matter whether of viral or bacterial origin – and even allergies. And with unexpected success: in a study recently published on Science, a team of researchers from Stanford University describes the promising results obtained from their new nasal spray, a broad-spectrum vaccine capable of immunizing for months against Covid, influenza, bacterial diseases and much more.
An unconventional vaccine
Traditional vaccines are necessarily specific: they work by presenting a piece (or antigen) of a virus or bacterium to our immune system, which thus learns to recognize it and produces specific antibodies to neutralize it. They are based on what is called “adaptive immunity”, a type of immune response that is created to be targeted, because it is calibrated against a specific target. This is an extremely efficient protection system, but it has some intrinsic limitations.
First, our immune system must have encountered a virus or bacteria before in order to neutralize it in this way. Secondly, adaptive immunity can be easily evaded by pathogens capable of rapidly mutating to become unrecognizable: this is the case, for example, of many seasonal viruses such as influenza, which can in fact reinfect us multiple times during our lives, and against which we must develop new booster vaccinations every year to keep protection active. For this reason, Stanford researchers decided to focus on another component of our immune system to arrive at a universal vaccine: the so-called innate immunity.
Another type of immunity
Innate immunity is the first form of protection our body has: a system of cells and biological processes (such as inflammation) that come into action at the site of an infection, to destroy pathogens and infected cells in a non-specific way. It serves to give adaptive immunity time to run its course, and produce the most powerful defenses that will eradicate the invader once and for all. As a rule, innate immunity remains active for a rather short period: a few days, a week at most. For this reason, it is usually not taken into consideration in the production of vaccines, which aim to generate long-lasting protection against diseases.
However, there is an important precedent: the Bcg vaccine (or Calmette and Guérin bacillus) against tuberculosis, a vaccine that contains an attenuated microorganism, developed in 1921 and still used today throughout the world in campaigns to prevent and eradicate this disease. Over the years it has been discovered that this vaccine not only provides protection against tuberculosis, but reduces mortality from many other infectious causes. In 2023, the authors of the new study demonstrated, for the first time, how it does this, highlighting a mechanism by which the Bcc vaccine manages to persistently activate innate immunity, thus protecting the children to whom it is administered from a wide range of infections for months, and not just weeks. Once the mechanism was found, it was just a matter of replicating it to see if it was possible to exploit it to create a universal vaccine. And that’s obviously what they did in the new study.
The universal vaccine
In the case of the BCG vaccine, the long-term activation of innate immunity is linked to the action of a particular type of T lymphocytes, cells that are part of the adaptive immune system and which, once attracted into the lungs by the vaccine, produce substances capable of stimulating the action of the innate immunity cells, and keeping them active for approximately three months. In their new nasal vaccine, the researchers therefore inserted a mix of molecules that mimic the signals sent by T lymphocytes, and a harmless antigen to attract these cells into the lungs. And they tested it on mice against the Sars-Cov-2 virus (the one that causes Covid 19).
Result: the untreated mice lost weight and died, the vaccinated ones were practically unaffected by the disease in any way. By studying what happens in the lungs of rodents, researchers have shown that the vaccine has a double action: it activates the innate immunity which reduces the viral load by 700 times, compared to that seen in a non-immunized mouse, and speeds up the action of the adaptive immunity, which begins to produce antibodies within about three days, compared to the two weeks it takes for unvaccinated animals.
Ready within seven years
The vaccine was therefore tested against other respiratory pathogens, such as Staphylococcus aureus and A. Baumannii, two bacteria that often cause hospital infections. And even against an antigen present in dust mites that cause respiratory allergies. And in all cases, it has proven to be extremely effective. Obviously, before claiming victory we will need to test the vaccine on humans to confirm its effectiveness and safety. And that’s what its inventors intend to do in the coming months. If everything goes well, the vaccine could reach the market within five, maximum seven years. And it would be a revolution in the prevention of seasonal respiratory diseases.
“Imagine receiving a nasal spray in the fall months that could protect you from all respiratory viruses — including COVID-19, influenza, respiratory syncytial virus, and the common cold — as well as bacterial pneumonia and early spring allergens,” emphasizes Bali Pulendran, a Stanford microbiology professor who led the research. “It would be an epochal turning point for medical practice.”