Vaccines: Definition, History, Ingredients, Types and Mechanism of Action

Vaccines are a type of biological preparation that can produce autoimmunity and prevent diseases after being inoculated into the human body, including bacterial vaccines, viral vaccines, and parasitic vaccines. In addition to preventing infectious diseases, modern vaccines have been expanded to prevent non-infectious diseases, and new vaccines such as therapeutic vaccines and physiological regulation vaccines have emerged.

Vaccine Definition

The World Health Organization (WHO) defines vaccines as: a class of heterologous pharmaceutical products that contain immunogenic substances, can induce the body to produce specific, active and protective host immunity, and can prevent infectious diseases, including preventive and therapeutic vaccines with infectious diseases as indications. Vaccines for animals are made from microorganisms (bacteria, viruses, mycoplasmas, chlamydia, leptospiras, etc.), microbial metabolites, protozoa, animal blood or tissues, etc., and are processed to prevent and treat specific infectious diseases or other related diseases. In general, antigenic biological products made from bacteria are called vaccines, and antigenic biological products made from viruses, spirochetes, rickettsiae and chlamydiae are called vaccines.

History of Vaccines

Vaccines are autoimmune preparations for preventing infectious diseases by artificially attenuating, inactivating or using genetic engineering to make pathogenic microorganisms (such as bacteria, rickettsia, viruses, etc.) and their metabolites. According to records, the earliest use of vaccines to block the spread of diseases was the use of human pox to prevent smallpox in the Song Dynasty. So far, the development of vaccines has been continuously developed and improved, and there are mainly several types of vaccines:

First-Generation Vaccines

Traditional vaccines are prepared by attenuating or inactivating pathogens. The successful development of this vaccine is inseparable from the contribution of French scientist Pasteur. When studying chicken cholera, Pasteur found that the virulence of Vibrio cholerae in chickens could be reduced after several generations of cultivation. After this attenuated bacterium was inoculated into chickens, the chickens not only did not cause disease, but also had immunity to Vibrio cholerae, thus inventing the first bacterial attenuated live vaccine. In 1881, Pasteur used the same principle to prepare anthrax attenuated vaccine. In 1884, the first viral attenuated live vaccine, rabies vaccine, was successfully developed, and Pasteur was also known as the "father of vaccines."

Second-Generation Vaccines

With the rapid development of molecular biotechnology, biochemistry, genetics and immunology, the use of recombinant technology to develop new vaccines is a new development direction of modern vaccinology. Genetically engineered subunit vaccines are based on DNA recombination technology. Genes encoding protective antigens of pathogenic microorganisms are introduced into specific vectors (such as Escherichia coli, yeast or insects, mammalian cells, etc.), and antigens (usually proteins) are synthesized by the expression system of the vector and separated, extracted, purified and processed to obtain vaccines. For example, hepatitis B vaccine belongs to this type of vaccine. Peptide vaccines use viral gene sequences to obtain the amino acid sequence of antigen proteins, and use amino acid synthesis technology to prepare polypeptide vaccines corresponding to viral antigens.

Third-Generation Vaccines

Nucleic acid vaccines are an emerging form of vaccine that can simulate natural infection to stimulate efficient immune responses. BNT162b2 is a lipid nanoparticle-delivered, nucleoside-modified RNA vaccine jointly developed by Pfizer, BioNTech and Fosun Group. Compared with the first and second generation vaccines, nucleic acid vaccines can make the body produce more targeted immune responses, and at the same time, they can use the body's cells to continuously produce antigen proteins, inducing the body's immune system to maintain immune responses for a long time. However, due to limitations in production scale, transportation conditions and further safety investigations, there is still a lot of work to be done to improve nucleic acid vaccines.

Vaccine Ingredients

• One of the key ingredients of vaccines is antigens, which are specific substances that stimulate the immune system to produce antibodies. These antigens can come from a weakened or inactivated form of the pathogen itself, or they can be fragments of the pathogen's proteins or genetic material.
• Adjuvants are another important ingredient in vaccines. These substances are added to enhance the body's immune response to the antigen. Adjuvants work by stimulating a stronger and longer-lasting immune response, thereby increasing the effectiveness of the vaccine. Common adjuvants used in vaccines include aluminum salts, which have been used for decades to enhance the immune response of vaccines.
• Stabilizers are also added to vaccines to help maintain the potency and efficacy of the vaccine during storage and transportation. These ingredients prevent the vaccine ingredients from degrading and help maintain their effectiveness until they are given to the patient. Common stabilizers used in vaccines include sugars, amino acids, and proteins.
• Preservatives are added to vaccines to prevent bacterial or fungal contamination during manufacturing and storage. These ingredients help ensure the safety and sterility of the vaccine by inhibiting the growth of harmful microorganisms.
• Emulsifiers and surfactants are added to some vaccines to help improve the dispersion of the vaccine ingredients and enhance their stability. These ingredients help ensure that the vaccine is mixed evenly, thereby increasing its effectiveness when it is given to the patient. Emulsifiers help mix the oil- and water-based ingredients in vaccines, while surfactants help reduce surface tension and facilitate the dispersion of particles.
• Some vaccines also contain stabilizers, such as gelatin, which help maintain the physical integrity of the vaccine formulation. These agents help prevent vaccines from losing potency or effectiveness due to changes in temperature or pH. Gelatin is often used in vaccines to help stabilize antigens and other ingredients.

PEG in Vaccines

Polyethylene glycol (PEG) is a synthetic, biocompatible polymer that is commonly used in vaccines as a stabilizer and to improve the solubility and bioavailability of active ingredients. In mRNA vaccines, which use fragments of genetic material from viruses to trigger an immune response, PEG plays a crucial role in protecting the fragile mRNA molecules from degradation and ensuring their effective delivery into cells. This is especially important because mRNA is inherently unstable and can be quickly broken down by enzymes in the body without proper protection. Additionally, incorporating PEG into the vaccine formulation also enables the formation of a protective lipid nanoparticle (LNP) coating around the mRNA molecules. This lipid layer not only protects the mRNA from degradation, but also helps cells to effectively absorb the vaccine, where the genetic material can be converted into viral proteins to stimulate an immune response. BOC Sciences is a leading supplier of PEG and its derivatives. With expertise in chemical synthesis and purification, our high-quality PEG products are designed to meet the specific requirements of vaccine manufacturers, ensuring consistency and reliability in formulation processes.

How Does a Vaccine Work?

The immune system is our body's defense mechanism against harmful invaders such as bacteria, viruses, and other pathogens. When a pathogen enters the body, the immune system recognizes its unique markers (called antigens) and launches a defense response to eliminate the threat. This response involves the production of specific proteins (called antibodies) that can target and neutralize the invading pathogen. Vaccines use the immune system's natural ability to provide protection against specific diseases. They contain weakened or inactivated forms of pathogens or their antigens, which are introduced into the body to stimulate an immune response without causing disease. By simulating the presence of a real infection, vaccines train the immune system to recognize and remember the pathogen's antigens so that it can respond quickly and effectively in future exposures.

When the vaccine is administered to the human body, it stimulates the human immune system to produce immune effector molecules (antibodies and cytokines) and immune effector cells, and ultimately eliminates the vaccine from the body. When a similar vaccine pathogen invades again, the immune system can quickly recognize and produce a large number of specific antibodies and immune effector cells by recognizing the characteristics of the pathogen, protecting the body from the pathogen. Therefore, the vaccine's action process can be divided into several key steps:

1. Administration: Vaccines are usually administered by injection, oral administration, or nasal spray, depending on the type of vaccine and the target disease. Once inside the body, vaccine components are recognized by the immune system as foreign invaders that need to be eliminated.
2. Recognition: The immune system, specifically the innate immune response, recognizes vaccine components as non-self and activates immune cells such as macrophages and dendritic cells to engulf and process the antigens.
3. Activation of adaptive immunity: The processed antigens are presented to specialized immune cells called T cells and B cells, which initiate the adaptive immune response. T cells play a vital role in coordinating the immune response, while B cells are responsible for producing antibodies specific to the antigen.
4. Antibody production: After encountering an antigen, B cells undergo a maturation and differentiation process to become plasma cells, which are specialized cells that secrete large amounts of antibodies. These antibodies circulate in the body, bind to and neutralize the antigen.
5. Memory formation: In addition to producing antibodies, B cells differentiate into memory B cells, which serve as long-term storage of immune memory. These memory cells are able to generate a rapid and powerful immune response upon subsequent exposure to the same pathogen, providing immunity to future infections.
6. Immune response: The coordinated efforts of antibodies, memory B cells, and other immune cells result in pathogens being eliminated before they can cause disease. By targeting and neutralizing antigens, the immune system can effectively destroy invading pathogens and clear infections from the body.
7. Long-term protection: Memory B cells generated during an immune response remain in the body for a long time, ensuring lasting immunity to a specific pathogen. This long-term protection is the hallmark of successful vaccination and is critical to preventing recurrent infections.

Types of Vaccines

With the rapid development of biotechnology, vaccine technology has been continuously upgraded and iterated, from traditional vaccines such as live attenuated vaccines, inactivated vaccines, and subunit vaccines to new vaccines such as genetic engineering vaccines, recombinant vector vaccines, and nucleic acid vaccines, and has made continuous progress and breakthroughs in immunogenicity and safety. According to the composition of immunogens, vaccines can be divided into three categories: whole microorganisms, subunits, and genetic materials.

Live Attenuated Vaccine

Attenuated vaccines are vaccines that weaken their toxicity and then inject them into the human body to stimulate the production of immune antibodies. The advantages of this type of vaccine are long immunity, fewer vaccinations, and high protective efficacy. The disadvantages are that the research time is long, the safety is not high, and if the human immunity is poor, the toxicity may be restored, which is dangerous. This type of vaccine includes attenuated live polio vaccine, attenuated live measles vaccine, and BCG vaccine.

Inactivated Vaccine

Inactivated vaccines are selected from pathogens with good immunity, cultured viruses or bacteria, and then treated by chemical means to retain the antigen activity of the virus, and finally made into vaccines. Its advantages are higher safety and relatively mature technology. The disadvantages are that the immune effect is relatively weak, multiple vaccinations are required, antibodies decrease rapidly over time, and the research and development time is long, which is not conducive to responding to the spread of sudden infectious diseases. Hepatitis A inactivated vaccine belongs to this type of vaccine.

Viral Vector Vaccine

Vector vaccine introduces antigen genes into the body through harmless microorganisms as carriers to induce immune responses. Its characteristics are that it combines the two advantages of strong immunogenicity of attenuated live vaccines and the accuracy of subunit vaccines. The disadvantage is that the antibodies against the vector in the body, whether they exist before or after immunization, will have a certain impact on the re-immunization effect of the corresponding vector vaccine. The vector of this type of vaccine is usually a vaccine strain of a specific microorganism, such as vaccinia virus, adenovirus, Vibrio cholerae, Salmonella, BCG, etc.

Component Vaccine

Component vaccine refers to a vaccine made from the main protective immunogen components of pathogenic pathogens.

• Peptide Vaccine

Peptide vaccine is a vaccine produced by synthesizing a segment of polypeptide based on the amino acid sequence of the virus, and is a vaccine prepared by chemical synthesis technology. There is only one peptide vaccine on the market in the world, namely the Cuban Cimavax-EGF vaccine approved for marketing in 2011, which is a therapeutic vaccine for stage IIIB and stage IV non-small cell lung cancer.

• Genetically Engineered Subunit Vaccine

Genetically engineered subunit vaccine is a vaccine made by cloning and expressing protective antigen genes using recombinant DNA technology. Genetically engineered subunit vaccines have high yield, good stability and good safety. HPV vaccine is such a vaccine.

• Polysaccharide-protein Conjugate Vaccine

Bacterial polysaccharide conjugate vaccine with protein as carrier refers to a polysaccharide-protein conjugate vaccine produced by chemically combining polysaccharides on protein carriers, which can improve the immunogenicity of polysaccharide antigens in bacterial vaccines. Polysaccharide vaccines have poor immunogenicity in humans, especially children. The 13-valent pneumococcal vaccine is such a vaccine.

Nucleic Acid Vaccine

Nucleic acid vaccines, also known as gene vaccines, include DNA vaccines and mRNA vaccines. Nucleic acid vaccines directly introduce genetic material that determines the immunogenicity of viruses or bacteria into the human body, rely on the body's own cells to produce antigens, and activate the immune system to produce immune responses. The difference between the two is that DNA is first transcribed into mRNA and then synthesized into antigen proteins, while mRNA is directly synthesized. Most of the new crown vaccines currently under development are mRNA vaccines. As the latest vaccine production technology, mRNA vaccines have obvious advantages. It does not rely on cell amplification, has a simple preparation process, a short research and development cycle, and has greatly improved vaccine production capacity. However, it also has certain disadvantages. Since mRNA is extremely easy to degrade, it needs to be delivered to the body with the help of special carriers, and the transportation and storage requirements are also very strict.

Based on this, the use of lipids in mRNA vaccine delivery has transformed the field of vaccinology. Lipids, an organic molecule that is insoluble in water but soluble in organic solvents, play a crucial role in the formulation of lipid nanoparticles (LNPs) used to encapsulate and protect mRNA molecules in vaccines. Lipid nanoparticles formed by lipids can encapsulate and protect fragile mRNA molecules. By encapsulating mRNA in lipid nanoparticles, the integrity and stability of mRNA are preserved, allowing it to reach the target cells intact and effectively deliver its genetic material for protein production. Lipid nanoparticles act as a protective shield, preventing mRNA degradation and ensuring its safe and effective delivery.

Toxoid Vaccine

Toxoid vaccines are toxins that lose their toxicity after being treated with formaldehyde, but still retain their immunogenicity. They are toxins that are then processed to become refined toxins. Commonly used toxinoid vaccines include diphtheria toxoid vaccines and tetanus toxoid vaccines.