What is Vaccine? and its Development History!

Vaccine

Vaccines refer to biological products made from various pathogenic microorganisms for vaccination. Vaccines made of bacteria or spirochetes are also called bacteriocin. There are two types of vaccines: live vaccines and dead vaccines. Commonly used live vaccines include BCG, polio, measles, and plague. Commonly used dead vaccines are the pertussis vaccine, typhoid vaccine, meningitis vaccine, cholera vaccine, and so on.

The production time of different vaccines varies, and some vaccines can take up to 22 months to produce a batch. The development of a vaccine is a long and complex process, and it is costly. Vaccination is the most economical and effective public health intervention for the prevention and control of infectious diseases, and it is also an effective means for families to reduce the occurrence of diseases among members and reduce medical costs.

Immunization is estimated to avert 2 to 3 million deaths each year from diphtheria, tetanus, whooping cough, and measles. Global vaccination coverage (the proportion of children worldwide who receive the recommended vaccine) has remained stable over the past few years.

Classification

There are two types of vaccines in China.

The first category of vaccines refers to the vaccines provided by the government to citizens free of charge, and citizens should be vaccinated by government regulations, including vaccines determined by the national immunization plan, vaccines added by the people’s governments of provinces, autonomous regions, and municipalities directly under the Central Government when implementing the national immunization plan, and Vaccines used for emergency vaccination or mass vaccination organized by the people’s government at or above the county level or its competent health department;

The second category of vaccines refers to other vaccines vaccinated by citizens at their own expense and voluntarily.

Principle

Vaccines are autoimmune preparations for the prevention of infectious diseases, which are prepared by artificially attenuating, inactivating, or using transgenic methods of pathogenic microorganisms (such as bacteria, rickettsia, viruses, etc.) and their metabolites. Vaccines remain the properties of pathogenic bacteria to stimulate the immune system of the animal body. When the animal body is exposed to this innocuous pathogen, the immune system will produce certain protective substances, such as immune hormones, active physiological substances, special antibodies, etc.; when the animal is exposed to this pathogen again, the immune system of the animal body will The system will follow its original memory and create more protective substances to prevent the damage of pathogenic bacteria.

Encyclopedia x Mixed Knowledge: Illustrated Vaccines

Type

Vaccines are generally divided into two categories: preventive vaccines and therapeutic vaccines. Prophylactic vaccines are mainly used for disease prevention, and the recipients are healthy individuals or newborns; therapeutic vaccines are mainly used for diseased individuals, and the recipients are patients.

According to tradition and habits, it can be divided into live attenuated vaccines, inactivated vaccines, antitoxins, subunit vaccines (including polypeptide vaccines), vector vaccines, nucleic acid vaccines, etc.

live -attenuated vaccine

Most viral vaccines of this type are more than 90% effective, and their protection usually lasts for many years. Its outstanding advantage is that the pathogen replicates in the host to produce an antigenic stimulus, and the number, nature, and location of antigens are similar to those of natural infection, so the immunogenicity is generally very strong, and even booster immunity is not required. This outstanding advantage is also potentially dangerous: infection can be triggered in some individuals with poor immunity; mutations can restore virulence. The latter can be more rationally attenuated with knowledge of the molecular basis of pathogenic virulence, possibly making it more certain that attenuating does not restore virulence.

Inactivated vaccine

Compared with live attenuated vaccines, inactivated vaccines use non-replicating antigens (dead vaccines), therefore, their safety is good, but the immunogenicity is also weakened, and immunization is often necessary. It should be noted that not all pathogens can be inactivated as highly effective vaccines: some of them are highly effective, such as Salk injectable polio vaccine (IPV) or hepatitis A vaccine; Short-duration vaccines, such as inactivated injectable cholera vaccines, have all but been abandoned; some partially inactivated vaccines have low efficacy and need to improve their protection rates and duration of immunity, such as traditional inactivated influenza and Typhoid vaccine. Most of these ineffective vaccines will be replaced by newer vaccines.

Toxoid vaccine

Toxoid vaccines are of great interest when the pathological changes of the disease are mainly due to potent exotoxins or enterotoxins, such as those for tetanus and diphtheria. In general, toxoids of enterotoxins are rarely successful. However, a genetically engineered detoxified variant of the heat-stable enterotoxin (LT) of enterotoxigenic E. coli holds promise as an effective vaccine for travelers’ diarrhea. Mutations corresponding to cholera toxin (CT) may become more important vaccines. Variants of these two toxins even induce good mucosal immunity and are promising mucosal immune adjuvants.

Most of the toxoid vaccines currently in use are manufactured using traditional techniques. These vaccines, such as diphtheria and tetanus vaccines, contain many impure components, and the formaldehyde treatment process, which turns the toxin into a toxoid, also results in cross-linking with bovine-derived polypeptides from the culture medium, ultimately producing unwanted antigens. Therefore, studying a mutated, non-toxic pure molecule as a new vaccine could improve the quality and efficacy of these vaccines, such as replacing glutamic acid at position 52 of diphtheria toxin with glycine, which can result in loss of toxicity and can cross-react with diphtheria toxin.

Subunit Vaccines and Peptide Vaccines

Recombinant DNA technology makes it possible to obtain a large number of pure antigen molecules. This is a revolutionary change in technology compared to vaccines made from pathogens, making the quality easier to control and the price higher. In terms of effects, some subunit vaccines, such as acellular pertussis, HBsAg, etc., have high immunogenicity at low doses; while other vaccines have lower immunity and require stronger adjuvants than aluminum salts.

Peptide vaccines are usually manufactured by chemical synthesis techniques. The advantage is that the composition is simpler and the quality is easier to control. However, as the molecular weight and structural complexity of the immunogen decreases, the immunogenicity also decreases significantly. Therefore, these vaccines generally require special structural designs, special delivery systems, or adjuvants.

Vector vaccine

Vector vaccines introduce antigen genes into the body through harmless microorganisms to induce immune responses. It is characterized by combining the strong immunogenicity of live attenuated vaccines with the accuracy of subunit vaccines. A significant benefit of this live vector vaccine is that it can effectively induce cellular immunity in vivo, which is promising in a context where current methods of inducing cellular immunity are not good enough and cellular immunity is particularly important in some diseases. Important vectors used in the test are variants of vaccinia virus, poliovirus, fowlpox virus, adenovirus, herpes virus, salmonella, shigella, etc. One or more cytokine genes can also be constructed at the same time, which can enhance the immune response or change the direction of the immune response.

Nucleic acid vaccine

Nucleic acid vaccines are also called DNA vaccines or naked DNA vaccines. Its key difference from live vaccines is that the DNA encoding the antigen does not replicate in humans or animals. The nucleic acid vaccine should contain a strong promoter element that can be highly expressed in mammalian cells, such as the middle-early promoter of human cytomegalovirus; it also needs to contain a suitable mRNA transcription termination sequence. After intramuscular injection, the DNA enters the cytoplasm and then reaches the nucleus of the muscle cell, but does not integrate into the genome. As the target cells of the gene gun method, muscle cells and dendritic cells do not have high-speed division and proliferation, and they do not have a high degree of homology with plasmids, so the possibility of homologous recombination is small.

Compared with other types of vaccines, nucleic acid vaccines have potential and enormous advantages: 

1. DNA vaccines are one of the few methods for inducing cytotoxic T cell responses; 

2. They can overcome protein subunit vaccines that are prone to misfolding and glycosylation It can solve the problem of incomplete transformation.

3. it has good stability, the possibility of a large number of variations is small, and it is easy to monitor the quality.

4. The production cost is low. 

5. Theoretically, multivalent vaccines can be realized by a mixture of multiple plasmids or by constructing complex plasmids. 

6. Theoretically, the stability of antigen synthesis will reduce the dose of booster injection, and a very small amount of DNA (sometimes in nanograms) can activate cytotoxic T cells well.

In theory, nucleic acid vaccines also have potential problems or side effects. First, although the possibility of homologous recombination with host DNA is small, random insertion is still possible. Although there are no quantitative data on this issue, whether it induces carcinogenesis remains a concern. Second, the titers of DNA vaccines differ between different antigens or different species. The effects of human vaccines in model animals should be properly evaluated. Third, the body’s immune regulation and effector mechanisms may lead to the destruction of antigen-expressing cells, resulting in the release of intracellular antigens and the activation of autoimmunity. Fourth, the stimulation of small doses of antigens for a long time may lead to immune tolerance, resulting in the non-responsiveness of recipients to antigens. However, in practice so far, these potential side effects have not been found.

Edible vaccine

The vector of this type of vaccine is to use the cells of edible plants such as potatoes, bananas, tomatoes, and to initiate a protective immune response by eating its fruit or other components. Plant cells as natural biocapsules can efficiently deliver antigens to the submucosal lymphatic system. This is one of the few effective forms of mucosal immunity currently available. Therefore, it has a good development prospect for mucosal infectious diseases. 

Contraindications

In my country, vaccine contraindications are used to be divided into general contraindications and absolute contraindications. Foreign books and periodicals call them contraindications and cautions.

General contraindications refer to delayed vaccination under certain circumstances, such as fever and disease recovery period (equivalent to a cautionary note).

Absolute contraindications refer to the possibility of increased probability of adverse reactions to vaccination, aggravation of adverse reactions, or immune damage after vaccination. Such as immune insufficiency (deficiency), can not receive the live attenuated vaccine, but can receive inactivated vaccine. Those who are allergic to eggs should not be vaccinated with vaccines such as measles and influenza, which are cultured with chicken embryo cells.

Referring to the 2003 ACIP recommendation in the United States, certain vaccines are optional for adults with certain health conditions. Patients with diabetes, chronic respiratory disease, chronic liver disease (including alcoholic liver disease), and heart disease can be vaccinated with influenza vaccine, pneumococcal vaccine (PCV), and hepatitis B vaccine; those with renal insufficiency can be vaccinated with pneumococcal vaccine, type B vaccine Hepatitis vaccine; immunocompromised persons can receive pneumococcal vaccine and varicella vaccine; HIV-infected persons can receive pneumococcal vaccine and varicella vaccine.

Coincidence

 Strictly speaking, the coincidence of vaccination can be divided into 3 situations: coincidence, induction, and aggravation of the original disease.

Coincidence means that the recipient is in the incubation period or prodromal period of a certain disease at the time of inoculation, and the disease occurs coincidentally after inoculation. It has no causal relationship with vaccination and is purely coincidental, that is, regardless of vaccination, this disease will inevitably occur. 

Induction means that the inoculated person has contraindications for vaccination specified in the vaccine instructions, the inoculated person or his guardian did not truthfully provide the inoculated person’s health status and vaccination contraindications before the inoculation, and the original disease of the inoculated person acutely relapsed or affected after the inoculation. physiological process.

Exacerbation means that the inoculated person has a chronic disease that causes aggravation or acute relapse immediately after vaccination, and the investigation has confirmed that it has a certain relationship with the vaccination. Exacerbation of the pre-existing disease is actually an induced one, but the Clinical symptoms and signs are more severe.

Induction and aggravation are directly or indirectly related to vaccination, that is, without vaccination, the recurrence or aggravation of the original disease may not be caused.

The “Regulations on the Administration of Vaccine Circulation and Vaccination” issued by the State Council stipulates that the inoculated person has the vaccination contraindications stipulated in the vaccine instructions, and the inoculated person or his guardian did not truthfully provide the inoculated person’s health status and vaccination contraindications before vaccination. The acute recurrence or aggravation of the original disease of the recipient after vaccination is not an abnormal reaction to prophylaxis.

Development History

The discovery of a vaccine is a landmark event in the history of human development. Because in a sense, the history of human reproduction is the history of human beings constantly fighting against diseases and natural disasters. The most important means to control infectious diseases is prevention, and vaccination is considered to be the most effective measure. Facts have proved that the same is true. The smallpox virus, which has threatened mankind for hundreds of years, was completely eliminated after the emergence of the vaccinia vaccine, ushering in the first victory for mankind to fight against the virus with vaccines, and it is even more convinced that vaccines can control and eliminate infectious diseases. effect. Over the past 200 years, the vaccine family has continued to expand and develop, and there are currently more than 20 vaccines used for the prevention and treatment of human diseases.

By Master James

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