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Adjuvants: Definition, Types, Mechanism, Role, Examples

What are Adjuvants, Definition, Classification, Types, Examples, Functions:

Adjuvants Definition:

  • An adjuvant is a substance that enhances the immune response to the antigen.

  • Adjuvants are the substances that increase immunogenicity of a vaccine formulation when added/mixed to it.

Adjuvants: Definition, Types, Mechanism, Role, Examples

What are adjuvants?

  • The word adjuvant (adjuvant) is derived from the Greek word "adjuvant".
  • Adjuvants can be injected at the same time or in advance with the antigen, which can effectively enhance the body's immune response to the antigen or change the type of immune response. 
  • Immune adjuvants have many advantages, such as reducing the number of immunization shots, reducing the amount of antigen, and enhancing immune responses.
  • There are many kinds of adjuvants; for example, aluminum hydroxide adjuvant, Corynebacterium pumilus, lipopolysaccharide, cytokines, alum, etc. 
  • Freund's complete adjuvant and Freund's incomplete adjuvant are the most commonly used adjuvants in animal experiments. 

Discovery of Adjuvants

  • In 1926, Glenny first discovered that aluminum adjuvant has an immune-enhancing effect.
  • In the 1930s, Freund invented Freund's adjuvant. 
  • In 1956, Johnson discovered that lipopolysaccharide endotoxin from Gram-negative bacteria has adjuvant activity.
  • In 1974, Ellouz et al. showed that muramyl dipeptide of mycobacteria also has adjuvant activity. 
  • In addition, immunostimulatory complexes (ISCOMs), liposomes, and biodegradable microspheres can also induce antibody production on mucosal surfaces. 
  • After that researchers have been working on the development of new vaccine adjuvants, but the only one approved for marketing is aluminum adjuvant. 
  • After the 1990s, several new adjuvants were successively approved for marketing, changing the history that aluminum adjuvants were the only adjuvants approved for human vaccines.

Classification of Adjuvants  : 

  • There are many types of adjuvants, and according to their functions, they can be divided into delivery systems and immunostimulatory adjuvants. The former includes the carrier, that is, a class of substances with immunogenic properties that can be combined with haptens, and also includes a class of substances that play a role in transporting and foiling the entire vaccine system. 
  • According to the source of adjuvant, it can be divided into bacterial, non-bacterial, microbial, cytokine, and synthetic. 
  • According to the physical and chemical properties, it can be divided into granular, gel, latex adjuvant, and so on. 
  • According to their properties, they can be divided into therapeutic adjuvants, immunostimulatory adjuvants, mucosal adjuvants, and genetic adjuvants.

Types of Adjuvants

Adjuvants generally include the following categories:

  1. Inorganic adjuvant: such as aluminum hydroxide, bright vanadium, etc.
  2. Biological adjuvants: such as Mycobacterium tuberculosis, BCG, Corynebacterium parvum, Pertussis bacteria, Gram-negative bacilli endotoxin, the B subunit of cholera toxin, muramyl dipeptide, and cytokines.
  3. Synthetic adjuvant: such as double-stranded polyinosinic acid: cytidylic acid (poly I: C), double-stranded poly adenosine acid: uridine (poly-A: U).
  4. Oil Adjuvants: such as Freund’s complete adjuvant, peanut oil emulsion, etc.
  5. Nano adjuvants:

Commonly used Adjuvants in Vaccines:

1. Aluminium salt adjuvant:

The adjuvant is approved for use in both human and veterinary vaccines. Adsorbing antigens on the surface of aluminum salts can induce tens times of humoral immunity with low cost. The disadvantage is that it cannot induce cellular immunity, the local stimulation is large, it is difficult to absorb, and it is easy to form cysts at the injection site. There are three common types of adjuvant: aluminum hydroxide, alum adjuvant, and tricalcium phosphate adjuvant, but AI(OH)3 adjuvant is commonly used. Such adjuvants are used in mycoplasma vaccines.

2. Liposome adjuvant:

The phospholipid bilayer is encapsulated in the form of concentric circles and has both adjuvant and carrier functions, similar to microspheres of cell membranes. Liposomes can deliver antigens to appropriate immune cells and have a targeting effect. Liposomes are non-toxic, non-immunogenic, and degradable in vivo, making them a good adjuvant. There are many reports confirming its effectiveness in the development of bacterial, viral, parasitic and tumor liposome vaccines.

3. Water-in-oil emulsion:

Antigens are encapsulated by oil to form microstructures, so that antigens are slowly released, mainly including complete Freund's adjuvant, incomplete Freund's adjuvant, white oil, etc. Water-in-oil adjuvant can stimulate the body for a long time and maintain good humoral immunity and cellular immune response, but the vaccine containing mineral oil adjuvant has certain side effects such as inability to metabolize after injection, causing allergic reactions, granulomas at the injection site, ulcers, or granulation of epithelial macrophages.

4. Propolis adjuvant:

Propolis is a natural adjuvant, which can improve the body's immunity, has anti-inflammatory, anti-viral and anti-oxidation effects, and cooperates with antigenic effects to enhance non-specific immunity. For example, avian cholera propolis vaccine. Propolis adjuvant has become the preferred adjuvant for bacteria or non-enveloped viruses.

5. Polysaccharide adjuvant:

Polysaccharide is a good biological response modifier and non-cytotoxic immune enhancer. It can not only activate cellular immunity and humoral immunity, but also activate the complement system and reticuloendothelial system through different pathways.

6. Levamisole adjuvant:

In 1971, Renoux et al found that the use of levamisole in combination with immune vaccines can enhance the immune effect. Levamisole can induce T cell differentiation, transform T cells into sensitized T cells, and then produce lymphokines such as MHF and MIF, and finally further activate macrophages. When the function of peripheral immune cells, T cells, macrophages and neutrophils is impaired, levamisole restores the impaired function. Levamisole generally has few side effects, but long-term use can cause diarrhea and liver damage.

Adjuvants Mechanism of Action:

There are various mechanisms and modes of action of adjuvants, which can be generally classified into three categories: 

(1) The formation of antigen reservoirs at the injection site can delay the rate of antigen release, prolong the immune response, and increase the number of immune memory cells, for example, minerals Colloids, emulsion adjuvants, etc. In the experiments of MC-Nicoll et al., the local antigen reservoir formed after vaccination prepared with PBP as an adjuvant can exist at the vaccination site for at least one year. 

(2) Some adjuvants have carrier functions, such as LSCOMS, liposomes, etc., which can change the physical state of antigens and the way they interact with the immune system. These novel adjuvant systems facilitate the phagocytosis of antigens by APCs and facilitate their entry into the lymphatic system. For example, the easy fusion of liposomes with antigen-presenting cell membranes can promote the phagocytosis of antigens in liposomes by APCs. In addition, since the antigen is concentrated on or inside the microparticles of the adjuvant system, the chance of the antigen reaching an effective concentration increases; for B cells, it will be possible to increase the degree of aggregation of immunoglobulin receptors.

(3) Adjuvants with direct or indirect pharmacological effects can change the functions of various cells involved in immune responses. Most adjuvants can elicit MHC-II type responses and promote antibody production in vivo.

Role of Adjuvants

  • An adjuvant is a substance capable of enhancing or altering the immune response to an antigen-specific to a vaccine component. 
  • They are commonly used to improve the effectiveness of a vaccine.
  • In vaccine preparations, the functions of adjuvants mainly include: enhancing the immunogenicity of vaccine antigens; promoting cellular and humoral immunity. 
  • Adjuvants are used to optimizing immune responses, and promoting immune responses in people with weak immunity. 
  • Adjuvants enhancing the transfer between antigens and mucosa As well as immune exposure. 
  • Adjuvants reduce the demand for antigens in vaccine components and the number of immunizations in the implementation process; 
  • Adjuvants optimize antigen structure, maintain antigen confirmation.

Frequently Asked Questions on Adjuvants:

Why do vaccines need adjuvants?
Answer: Vaccines (antigens) need to stimulate the body to produce specific immunity, and adjuvants have the following properties:
  • Enhance the surface area of ​​the antigen;
  • Enhance the synergistic effect of T lymphocytes and B cells;
  • Extend the storage time of antigens in tissues.
  • Causes cell infiltration at the inoculation site; Accelerates lymphocyte transformation;
  • Cause changes in cell membrane and cytoplasm;
  • Changes in cell function;
  • Non-specific immune enhancement

Why Adjuvants are added in Vaccines?
Answer: Components of vaccines include antigens, adjuvants, preservatives etc. The adjuvant in the vaccine is to strengthen or maintain the stability of the antigen; the preservative is to prevent the antigen from spoiling.

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