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Vaccine is an autoimmune preparation for preventing infectious diseases by artificially attenuating, inactivating or using genetically modified microorganisms (such as bacteria, rickettsia, viruses, etc.) and their metabolites. The vaccine retains the characteristics of the pathogen to stimulate the immune system of the animal. When the animal is exposed to this non-invasive 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 the pathogen again, the animal’s immunity system will follow its original memory and create more protective substances to prevent the damage of pathogens.
Vaccines generally fall into two categories: preventive vaccines and therapeutic vaccines. The preventive vaccine is mainly used for the prevention of diseases, and the recipient is a healthy individual or a newborn; the therapeutic vaccine is mainly used for the sick individual, and the recipient is the patient.
According to tradition and habit, it can be divided into live attenuated vaccine, inactivated vaccine, antitoxin, subunit vaccine (including peptide vaccine), carrier vaccine, and nucleic acid vaccine, etc.
1. Nucleic acid vaccine
Nucleic acid vaccines are also known as DNA vaccines or naked DNA vaccines. It differs from the key to live vaccines in that the antigen-encoding DNA does not replicate in humans or animals. The nucleic acid vaccine should contain a strong promoter element capable of high expression in mammalian cells such as the human early cytomegalovirus promoter; it also contains a suitable mRNA transcription termination sequence. After intramuscular injection, DNA enters the cytosol and then reaches the nucleus of the muscle, 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 are not highly homologous to the plasmid, so the possibility of homologous recombination is small.
Compared with other types of vaccines, nucleic acid vaccines have potential and great advantages:
(1) DNA vaccine is one of the few methods to induce cytotoxic T cell responses.
(2) DNA vaccine can overcome protein subunit vaccines susceptible to unfolding and glycosylation incomplete problem.
(3) Good stability, a large number of mutation possibilities, easy to quality control.
(4) Lower production costs.
(5) Theoretically, multivalent vaccines can be achieved by a mixture of various plasmids or by constructing a complex plasmid.
(6) Theoretically, good stability of antigen synthesis will reduce the booster dose, and very small amounts (sometimes nanograms) of DNA will activate cytotoxic T cells.
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 is no quantitative data on this issue, whether or not to induce cancer is still a concern. Second, the difference in titer of DNA vaccines between different antigens or different species. The effect of human vaccines on model animals should be properly evaluated. Third, the body’s immune regulation and effector mechanism may lead to the destruction of antigen-expressing cells, leading to the release of intracellular antigens and activation of autoimmunity. Fourth, stimulation of long-term low-dose antigens may lead to immune tolerance, resulting in the recipient’s lack of reactivity to the antigen. However, these potential side effects have not been discovered in practice so far.
2. Subunit vaccine and peptide vaccine
DNA recombination technology makes it possible to obtain large amounts of pure antigen molecules. This is a revolutionary change in technology compared to vaccines prepared from pathogens, making quality easier to control and more expensive. In terms of effects, some subunit vaccines, such as non-cell pertussis and HBsAg, are highly immunogenic at low doses; others have lower immunity and require stronger adjuvants than aluminum salts. Peptide or protein vaccines are typically manufactured by chemical synthesis techniques. The advantage is that the ingredients are simpler and the quality is easier to control. However, as the molecular weight of the immunogen and structural complexity decrease, the immunogenicity is also significantly reduced. Therefore, these vaccines generally require special structural designs, special delivery systems or adjuvants.
To be continued in Part Two…