An adjuvant is a non-specific immunopotentiator that, when injected with an antigen or pre-injected into the body, enhances the body's immune response to the antigen or alters the type of immune response.

There are many kinds of adjuvants; for example, aluminum hydroxide adjuvant, Corynebacterium parvum, lipopolysaccharide, cytokine, alum and the like. Freund's complete adjuvant and Freund's incomplete adjuvant are the most commonly used adjuvants in animal testing.

Mechanism: The mechanism of adjuvant enhancing immune response is to change the physical shape of antigen, prolong the retention time of antigen in the body; stimulate the ability of mononuclear phagocytic cells to present antigen; stimulate lymphocyte differentiation and increase the capacity of expanding immune response.

Function: Since the adjuvant can enhance the surface area of ​​the antigen and prolong the retention time of the antigen in the body, so that the antigen has sufficient contact time with the cells of the lymphatic system, it has the following effects: (1) converting the antigen-free substance into an effective antigen. (2) enhance the level of circulating antibodies or produce more effective protective immunity; (3) change the type of circulating antibodies produced; (4) enhance the ability of cell-mediated hypersensitivity; (5) produce experimental Autoimmune or other types of allergic diseases; (6) Protect antigens (especially DNA, RNA) from decomposition by enzymes in the body.



The development of adjuvant:

Overview of Immunoadjuvants In immunology, an adjuvant refers to a substance that is capable of enhancing or modulating an antigenic humoral or cellular immune response. Adjuvants help to induce early, strong, and prolonged immune responses with a limited number of antigens. To be the focus of research on purified vaccines, subunit vaccines and DNA vaccines, these vaccines are less immunogenic and require adjuvants to activate the immune response. With the deepening of immunology research and the rapid development of genetic engineering technology, the research of adjuvants is becoming more and more important in modern immunology based on the pursuit of immune effects and reduced production and use costs. By increasing the effect of the adjuvant, reducing the amount of antigen and reducing the toxic side effects on the body is an important indicator of an ideal adjuvant.

Research status of vaccine adjuvants:

Prior to 2009, aluminum adjuvant was the only adjuvant approved by the US FDA for human vaccines.However, because the aluminum adjuvant vaccine induces an unsatisfactory Th1 immune response and weak cellular immunity, and the vaccine supplemented with aluminum compounds cannot be cryopreserved, limiting the extensiveness of aluminum adjuvants in vaccine use, it is looking for alternatives. Adjuvants are imminent. In the study of all alternative adjuvants, including inorganic adjuvants, oil adjuvants, etc., liposome adjuvants are the most promising one. In 1974, Gregoriadis and Alliso reported for the first time the use of liposomes as immunological adjuvants. Since then, liposomes and related vesicle carriers have been widely used as infectious agents and cancer vaccines as highly effective adjuvants for inducing humoral and cellular immunity. Currently, at least eight liposome adjuvant vaccine systems are approved for human use or in clinical trials [5]. Among them, the Swiss flu vaccine Inflexal V and the hepatitis A vaccine Epaxal are the only two liposome adjuvant vaccines currently on the market.

Liposomes:



The liposome of the liposome was first produced by the British scholar Bangham in 1960 and refers to an ultra-micro spherical drug carrier preparation prepared by encapsulating a drug in the middle of a film formed by a lipid-like bilayer. It is a closed vesicle composed of a lipid bilayer and having an aqueous phase inside, and has the function and characteristics of a biofilm.

Liposomes are mainly composed of phospholipids and other additives. Phospholipids form bilayers in liposomes.

High liposome stability and targeting. Due to the particularity of the liposome encapsulating material, it has many advantages, such as: biocompatibility, targeting, sustained release, and increased drug stability.

Preparation of liposomes Traditional thin film evaporation methods are the most basic and widely used methods in liposome preparation. This method is simple, easy to operate and suitable for laboratory research. The influenza virus is an envelope virus and is sensitive to organic solvents such as diethyl ether and chloroform. Influenza vaccine liposomes were prepared by passive evaporation of membrane evaporation, which avoided direct contact of the vaccine with organic solvents. The main problem is that imperfect processes, residues of organic solvents or surfactants can lead to a decrease in the biological activity of protein drugs, and it is difficult to prepare large-volume liposomes.

The effect of liposome physicochemical properties on its immunogenicity The effect of the main physicochemical properties of liposomes on the immunogenicity of liposome influenza vaccines is systematically studied, laying the foundation for the application of liposomes as adjuvants for influenza vaccines. Theoretical basis. After 35 years and more than 1,300 studies, it is clear that the physicochemical properties of the liposome are extremely important for its immunogenic effects. What has a greater impact on immunogenicity includes:

The method of coating the antigen. Determine the speed of antigen release and the difficulty of identification by APC.

Liposomal composition, charge, particle size, and the like. Can change the pharmacokinetic properties of liposomes to achieve ideal retention and antigen capture Take, process and present on MHC molecules. Mann et al. found that small particle size liposomes stimulated a stronger Th2 response, and large-diameter-stimulated Th1 responses were stronger (higher levels of IFN-r and IgG2) and stimulated stronger protective antibodies. The particle size is also critical for the transport, uptake, and processing of antigens to lymph nodes. Large particles are easily taken up by DC, small particles are lymphatic Knot transport, ingested by MP and DC. It is suggested that the ingestion site is related to the particle size. Small particles are easy to reach the lymph nodes, inducing IgG2 antibody, B cell nuclear CD8 + T cell immune response. Positively charged liposomes reduce the stability of the cell membrane by forming an electron pair complex with the negatively charged cell membrane, allowing the antigen to be more efficiently delivered to the cytoplasm. Large particle, positively charged liposomes are strongly phagocytized by APC.

Prospects for adjuvants:

Adjuvants are combined with different antigens, and their non-specific immunomodulatory effects are unpredictable, so the approval of the adjuvant is bound to a specific antigen, rather than as a separate adjuvant. Therefore, the mechanism of action of simple liposome as an adjuvant cannot be fully interpreted, and it has no great research value unless it is bound to a specific antigen. In addition to immunity pathways and antigen dosage also have a significant impact on the immunogenicity of specific liposome vaccines.