Named by experts to fight against Omicron, what is “vaccine adjuvant”?

With the arrival of Omicron and the increase in breakthrough infections, in addition to developing a vaccine specifically for the Omicron variant, many experts have also "specifically" emphasized the need to pay attention to the huge potential of vaccine adjuvants in blocking the spread of the virus.

Most people have only heard of vaccines, but not adjuvants.

So what exactly are adjuvants?

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Vaccine adjuvant system: not in the center, but better than the center

In a small bottle of solution of the inactivated new coronavirus vaccine that we commonly use, in addition to the effective antigen (the main component of the vaccine that can stimulate an immune response), there is also an adjuvant system whose main component is aluminum hydroxide (or aluminum phosphate), which plays a role in adsorption and immune enhancement.

In fact, adjuvants work before the vaccine enters the body. For example, through adsorption, they can prevent antigens from "hanging on the wall" and ensure that the full dose is injected.

After entering the body, adjuvants can also enhance the immune response. Some theories believe that aluminum adjuvants micronize soluble antigens and stimulate the phagocytosis of dendritic cells. Others believe that adjuvants lock antigens on presenting cells and enhance antigen presentation. In short, adjuvants may enhance the body's immune response through different pathways.

In short, the adjuvant system can stabilize antigens and activate immunity. In this way, the adjuvant system is a bit like "a minister who can reach the emperor and the people". Therefore, although it is not in the C position, it is better than the C position.

It should be noted that not all vaccines require adjuvants. For example, the adenovirus vector vaccine for the new coronavirus does not require an adjuvant, so it can be made into an inhaled vaccine through aerosolization.

Research started from a rumor: Adjuvants come on the scene

In 1925, Gaston Ramon began an experiment that even he described as "a little interesting."

A few years ago, the French veterinarian was trying a new diphtheria vaccine in horses when he made an unexpected discovery: Some animals developed nasty abscesses at the injection site, and those animals also tended to mount a stronger immune response. It got him thinking—what else could he add to the vaccine to encourage that to happen?

In the 1920s, French veterinarian Gaston Ramon used household staples, including breadcrumbs, in his early experiments with adjuvants.

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Over the next year, Raymond tested a range of strange ingredients that looked like what he happened to have in his cupboard. Along with the diphtheria vaccine, he injected his hapless animal patients with tapioca, starch, agar, lecithin (an oil emulsion commonly found in chocolate), and even breadcrumbs.

The experiment was successful. The animals that had been given the Ramon mixture produced significantly more antibodies than those that had been given the vaccine alone without these additives, suggesting that the mixture was better at protecting against diphtheria.

Thus was born the field of adjuvants. Named after the Latin word adjuvare, meaning "help" or "aid," these substances can be added to vaccines to make them more effective. They're still widely used today, and they're every bit as weird as they were when they first came out.

Adjuvant innovation can stimulate cellular immunity to “kill” viruses

Many life-threatening infectious agents (such as HIV, hepatitis C virus, Mycobacterium tuberculosis, and Plasmodium, the parasite that causes malaria) have ways of evading antibodies, so vaccines must stimulate a robust T-cell response if they are to be effective against them. In fact, research into combating these difficult microbes has led to a renewed interest in vaccine adjuvants and breakthroughs in our knowledge of the immune system, which has led to the creation of better adjuvants.

Cellular immunity is essential to "wipe out" the virus in infected cells. New adjuvants have been favored in recent years because they can stimulate cellular immunity. If new adjuvants can act on this recognition receptor, then the signal brought by the vaccine will be better transmitted to the immune system, thereby triggering better humoral immunity (neutralizing antibodies) and cellular immunity.

At present, there are only five new adjuvants approved for use worldwide. In my country, the adjuvants used are relatively simple, and most of them are aluminum adjuvants.

Aluminium in vaccines is always in the form of salts such as aluminium hydroxide.

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It is estimated that vaccines save 2 to 3 million lives each year and prevent lifelong disabilities. No one can quantify exactly how much of this success is due to vaccine adjuvants. However, by enhancing the body's response to vaccination, adjuvants can make vaccines more effective and protect the body longer. Some statistics show that, for example, some vaccines simply do not work in the elderly without adjuvants.

Rumor debunked: Aluminum adjuvant in COVID-19 vaccine does not harm the brain

Previously, there were rumors that the COVID-19 vaccine could not be used because the aluminum adjuvant nanoparticles (AAN) in the vaccine could not be digested by macrophage (MF) enzymes and would cross the blood-brain barrier (BBB) ​​and be transmitted to the brain, causing damage and affecting human health. Is this true?

In fact, some of the most basic concepts are extremely wrong.

First, the diameter of aluminum hydroxide (or aluminum phosphate) particles used in vaccines is generally 1-10μm, which is far from the level of "nanoparticles", so there is no such risk. Secondly, aluminum hydroxide is simply impossible to pass through the blood-brain barrier, because the upper limit of the molecular diameter allowed by the pore size of the blood-brain barrier is usually only 1nm (1μm=1000nm), and aluminum hydroxide particles have no chance of getting through, let alone getting stuck.

In addition, after vaccination, only a very small amount of aluminum will enter the blood circulation because the adjuvant acts to absorb the antigen, but that amount of aluminum is far lower than the concentration that may cause risks, and is even less than the amount consumed from vegetables and fruits on a daily basis.

Why these seemingly random ingredients are so important to vaccines has been a mystery for more than a century. Now scientists are racing to uncover their secrets.

Comprehensive sources: Xinhua News Agency, Science and Technology Daily, Beijing Daily, China News Service, Global Health Drug Development Center official Weibo, etc.