Past and present of adjuvants
The invention of the vaccine originated from the great practice of vaccination to prevent smallpox during the Northern Song Dynasty in China. In the 17th century, the introduction of this technology to Europe greatly enlightened the development of modern immunology. After a variety of major technological innovations such as improvement of vaccinia, screening and culture of attenuated microorganisms, and antigen inactivation technology, the end of the 19th century to the beginning of the 20th century can be regarded as the first golden age of vaccine development. However, the vaccine at that time needed to consume a lot of pathogenic microorganisms as antigens, and the cost was very high; and the vaccine efficiency was not stable enough. These problems did not change until an unexpected experiment led to the invention of adjuvants.
In 1925, when French veterinarian Gaston Ramon prepared an antiserum against diphtheria toxin (used to inhibit protein synthesis in mammals), it was accidentally discovered that horses with abscesses or even ulcers on immune sites produced more antibodies in their blood. The effect is also better. Based on this observation, he unexpectedly added some breadcrumbs, tapioca flour, etc. to the diphtheria toxin antigen as additives to cause inflammation in the immunized animals, thus greatly improving the efficiency of antibody production.
Ramon named these additives that promote antibody production as “adjuvants” for the first time. The word Adjuvant is derived from the Latin “Adiuvare”, which has the meaning of help and assistance.
Later, when British immunologists were purifying and enriching diphtheria toxoid, they were surprised to find that the reagent used in precipitating the toxin protein—potassium aluminum sulfate (ie alum) can make the vaccine produce better antibody response and reduce the antigen in the vaccine. The dosage.
The “Accelerator of Adaptive Immunity”
The great success of adjuvants stems from innovative practice. Immunologists have gradually discovered that the immune system is divided into natural immunity and adaptive immunity. The adjuvant, like a highly effective natural immune agonist, can accelerate the initiation of adaptive immunity.
If the vaccine is compared to a bullet, then the antigen in the vaccine is the bullet’s warhead; and the adjuvant is more like the gunpowder behind the warhead, which is responsible for pushing the warhead out more powerfully, breaking through the natural immune barrier, and adapting The bullseye of sexual immunity leaves the “bullet” of the vaccine antigen-immune memory.
A vaccine without an adjuvant is like a stone fired by a slingshot, which is soft and weak. A vaccine with a proper adjuvant is an armor-piercing bullet that can usually get twice the result with half the effort.
Aluminum-the “outstanding” among adjuvants
The invention of aluminum salt adjuvants has a history of nearly a hundred years. At present, in addition to potassium aluminum sulfate, aluminum adjuvants are mostly in the form of aluminum hydroxide or aluminum phosphate. Although the safety and effectiveness of aluminum salt adjuvants have been tested in history, with the development and iteration of vaccine technology, traditional aluminum salt adjuvants have become more and more ineffective. At this time, it is necessary to add more active adjuvants to enhance the immune response to produce better results.
With the deepening of immunological research, people have had more and more methods on how to efficiently mobilize the immune system. However, the inorganic aluminum salt adjuvant has a strong cost due to its simple composition and diverse sources. Competitiveness is still outstanding among adjuvants.
New generation adjuvant concept
It is worth noting that the pioneering research and creation of manganese salt adjuvants by Chinese scientists has become the next hot spot for adjuvant research. On the one hand, manganese ions can simulate the immune alarm signal during virus infection, directly activate the anti-viral natural immune response, and efficiently initiate adaptive immunity to generate immune memory. On the other hand, manganese salt adjuvants and aluminum salt adjuvants are both inorganic compounds, which can be extracted and prepared from China’s abundant minerals, with a wide range of sources and low cost.
More importantly, manganese is a nutrient element that can be absorbed and metabolized by the human body. It is an essential trace mineral for the human body. Compared with aluminum, which cannot be completely metabolized by the human body, its safety is also worth looking forward to.
In the history of human existence, vaccines have saved more lives than any other medical treatment. Since the effect of adjuvants was discovered a hundred years ago, scholars have been continuously studying the mechanism of adjuvants. We look forward to better adjuvants to “adjuvant” the development of better vaccines and save more life.