Shark liver and soap tree: why strange substances are added to vaccines
Many vaccines contain strange substances, such as aluminum or shark liver extract. The fact is that most vaccines do not work without them, but no one knows why, writes Air force.
1925 Gaston Ramon begins an experiment that he himself calls "interesting."
For several years, a French veterinarian was testing a new diphtheria vaccine on horses and suddenly made an unexpected discovery. In animals that had an unpleasant abscess at the site of inoculation, the immune response was stronger.
And the doctor began to speculate what else could be added to the vaccine to facilitate this process.
Over the next year, Ramon tasted an original complex of ingredients that he apparently found in his kitchen. Together with the diphtheria vaccine, his unfortunate patients were injected with tapioca, starch, agar, lecithin (an emulsion of the oil usually found in chocolate), and crackers.
The experiments were successful. Animals given vaccines with Ramon's crazy ingredients had far more antibodies than those given the unaddressed vaccine.
In other words, additional components improved the body's defenses against diphtheria.
So a whole branch of pharmacology arose, studying adjuvants - substances designed to accelerate and enhance the action of the main component of drugs.
Adjuvants are used to this day - and now they are no less amazing than they were originally.
The most widely used adjuvant in the world is aluminum. This chemical is found in most vaccines, particularly DTP, as well as vaccines for hepatitis A, hepatitis B, human papillomavirus, Japanese encephalitis, meningitis B, anthrax, pneumococcus, and haemophilus influenza b.
Other popular ancillary ingredients include squalene. It is an oily substance made from shark liver and quillaya tree bark extract, from which Native Americans make soap.
The newest supplements (they haven't even been licensed yet) are perhaps the most amazing of all. These are separated from the body the tails of bacteria and "bacterial ghosts" made from the empty shell of microorganisms.
Vaccines are known to save the lives of two to three million people each year and prevent disability for life.
How much of this success comes from adjuvants has not been studied.
But by making the body respond more strongly to the vaccine, they make the vaccines effective and provide longer lasting protection than would be possible without them. In some age groups, such as the elderly, certain vaccines would have no effect at all without adjuvants.
“Without an adjuvant, antibodies usually disappear after a few weeks or months. And with them they can last for several years, ”says Bingbing San, a chemical engineer at Dalian University of Technology in China.
But why these random components play such an important role in vaccination has remained a mystery for over a century. However, now scientists are trying to unravel it.
However, while these bizarre ingredients in vaccines are daunting, they are added in microscopic amounts. For example, a typical dose of a vaccine contains only 0,2 mg of aluminum, which is less than a single poppy seed weighs.
There is also no evidence that any of the adjuvants so far used have side effects.
In fact, it is because of their safety that adjuvants have become so popular.
Back in the 1970s, pediatric neurologist John Wilson gave a speech at the Royal Society of Medicine, announcing that 36 children suffered brain damage after being vaccinated against whooping cough.
Despite the fact that he was wrong, the story received a huge resonance. It was picked up by journalists, and in subsequent years, pertussis vaccination in the UK fell by more than half. And in some countries it was stopped altogether.
The fears were not true - the vaccine has been widely used for decades without incident. But she did have several negative side effects, such as fever, which were easily mistaken for something dangerous.
Ultimately, the scandal prompted scientists to look for new ways to make vaccines.
Previously, most of them were made using either live, but weakened microorganisms, which helped the body to recognize them, or dead whole.
The latter also applied to the whooping cough vaccine, which was given along with tetanus and diphtheria (DTwP).
These vaccines were sometimes accompanied by temporary symptoms because they mimicked natural infections. And just like natural infections, they were highly effective in building immunity that could last for decades.
Many vaccines that contain live microorganisms also provide additional protection against non-vaccine-related infections, with many benefits to humanity.
The new approach was radically different. After the panic caused by whooping cough, scientists began to include only certain parts of the microorganisms, such as the toxins they produce or fragments of their outer surface. These new vaccines were just as safe and much more convenient to use. True, there was one “but”.
Vaccines made in this way were less "immunogenic", that is, the protection against them was less reliable and lasted less. To solve this problem, scientists turned to adjuvants.
The aluminum paradox
Aluminum is not only the most common adjuvant, but also one of the oldest.
Soon after Ramon discovered that his horses responded better to vaccines with added cooking ingredients, British immunologist Alexander Glennie made another accidental discovery.
In 1926, his team tried to cleanse the toxin produced by the diphtheria bacteria so that it would not dissolve so quickly in the body. The researchers hoped the toxin would stay longer at the injection site and trigger a stronger immune response.
For this, Glenny tried to use aluminum salts. Legend has it that this was the first thing he saw on the shelf of chemicals in his laboratory - who knows, they may have been alphabetically ordered.
But when he inoculated the freshly made diphtheria toxin in guinea pigs, something unexpected happened. Animals that received the toxin with aluminum salts produced much stronger immunity, and the reason was precisely the use of aluminum.
Aluminum is still added to vaccines in the form of salts. These are usually aluminum hydroxide (also used for heartburn), aluminum phosphate (found in dental fillings), and aluminum potassium sulfate, which is sometimes found in disintegrants.
One of the explanations for the action of aluminum is the toxicity of its salts. They cause cells to release uric acid, which activates the immune response.
Immune cells are sent to places where foreign microorganisms are found - and voila, the vaccine worked.
Another idea is that the Nalp3 receptor plays a central role in the grafting process.
Studies have shown that the aluminum in vaccines activates this receptor, which acts as an alarm, warning the rest of the immune system.
However, while there are many different types of adjuvants and many potential mechanisms of their action, in fact they all attract the attention of the immune system.
This enhances the memory in the immune system of the pathogen, therefore, immunity against it lasts longer.
Take squalene, an oil made from shark liver. It is a key ingredient in MF59 adjuvant.
It is already being added to seasonal flu vaccines and is currently being researched for use in COVID-19 vaccines.
(Incidentally, this raised concerns that the production of a vaccine against COVID-19 for the entire population of the planet would require the destruction of about 250 sharks. The estimates, however, are rather dubious).
MF59 triggers the release of chemokines (signaling chemicals) in neighboring cells, which in turn stimulates other cells to release more chemokines.
Ultimately, this cascade attracts immune cells that absorb the vaccine - in particular the recognizable parts of the pathogen it protects against - and transport it to the lymph nodes, which filter pathogens from the body and help identify infections.
“Vaccine developers are very conservative people,” says Sun. “So every time they try to find an adjuvant for a new type of vaccine, they turn to time-tested, safe and effective options.”
However, scientists began to wonder if they could come up with something better than substances accidentally invented in the 1920s and 1950s, when DNA was still unknown, they did not fly to the moon, and computers either did not exist, or they were the size with a house.
This is especially important because of a tragic irony: the people who are most vulnerable to infections tend to have weak immune responses to vaccines.
And this is very true for vaccines for COVID-19, a disease that kills people over 80 more often than people under 50.
Considering that the number of 70-, 80-, 90- and 100-year-olds in the world is growing, this problem will only get worse.
This is why the development of a new generation of effective adjuvants is so important.
One of the new candidates is the flagelin protein. It is found, for example, in the bacteria of Salmonella, more precisely in their tails, with which they move.
Flagelin is produced by separating the tail from the body of bacteria, although it has recently begun to be grown in genetically modified cells.
Flagelin has not yet been approved for use in human vaccines, but has shown very positive results in trials.
Another option is the so-called bacterial ghosts, which are made up of empty shells of bacteria. They are formed by splitting open bacterial cells, such as Escherichia coli, leaving only the cell membrane.
Like squalene-based adjuvants, they produce chemical signals that call immune cells for help and draw their attention to the vaccine.
“Developing adjuvants is a painstaking job,” Bingbing Sun explains. “You have to make sure they are both safe and effective, and that takes time. It takes an average of 10-12 years to license a conventional vaccine. ”
Who knows, maybe almost a century after Gaston Ramon experimented with bread crumbs, we will have new adjuvants. However, the next generation of supplements can be as fancy as the first.
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