DNA vaccines are a type of nucleic acid vaccines, which are also called genetic vaccines. The plasmid vector containing the encoded protein gene sequence is introduced into the host by intramuscular injection or microprojectile bombardment, and the antigenic protein is expressed by the host cell, thereby inducing the host cell to generate an immune response to the antigen protein to prevent and treat the disease.
Nucleic acid vaccines are developed by modern biotechnology means, including immunology, biochemistry, molecular biology, etc. They are divided into DNA vaccines and RNA vaccines. At present, the research on nucleic acid vaccine is mainly based on DNA vaccine. DNA vaccines are also known as naked vaccines. After the DNA vaccine is introduced into the host, it is taken up by the cells, and the protein antigen of the pathogen is expressed in the cells, and the cellular immunity and humoral immunity are stimulated by a series of reactions.
The immune mechanism of the nucleic acid vaccine is illustrated as follows:
- Nucleic acid vaccine is a nucleic acid-mediated immunization vaccine developed in recent years.
The essence is that the eukaryotic expression vector containing the pathogen antigen gene can be taken up by the body cells and express the antigenic protein of the pathogen when it is introduced into the body, thereby inducing the body’s immune response to the protein. A systemic or local immune response can be triggered as the route and location of the introduction differs. In a systemic immune response, both humoral and cellular immunity can be induced.
- Nucleic acid vaccine can trigger a comprehensive immune response
When a protective antigen gene with a highly expressed regulatory sequence is introduced into an animal’s somatic cell, only a small amount is taken up by the cell and enters the nucleus. Under the control of the promoter on the vector, the antigen gene mRNA is transcribed, and the latter enters the cytoplasm and is translated. Corresponding antigenic protein.
- Nucleic acid vaccine can also induce local immune response and immune memory
If a gold granule coated with a nucleic acid vaccine is introduced into the mucosa by a gene gun, it may be taken up and expressed by lymphocytes or mucosal epithelial cells in the mucosa-associated lymphoid tissue under the mucosa, and the produced antigen protein is easily localized by the antigen. The presenting cells (APC) recognize, ingest, process and present to TH cells, further activating B cells in local lymphoid follicles to differentiate into plasma cells and Bm cells, which produce immune memory, the former can synthesize IgA, and the IgA monomer has a J chain linked together. When passing through the mucosa, the secretory sheet produced by the mucosal epithelial cells is linked to the dimeric IgA, and the stable secretory type IgA is discharged together with the mucosal secretion, distributed on the mucosal surface, in the mucosal part. It plays a very important role in defense against infection.
So, here comes with the question: how does the DNA vaccine work?
The mechanism of action and influencing factors of DNA vaccine
The DNA vaccine is a new vaccine in 1990, also known as a nucleic acid vaccine. The DNA vaccine clones a foreign gene encoding an antigenic protein into a eukaryotic plasmid expression vector, introduces the recombinant plasmid directly into the animal cell, and allows the foreign gene to express the antigenic protein in the animal through the transcriptional system of the host cell. Thereby inducing the host to produce an immune response to the antigenic protein for the purpose of preventing and treating the disease.
DNA vaccine can stimulate the body-specific immune response, has a long immunization period, has the advantages of low production cost, easy mass production and preservation, and is a new generation vaccine with application prospects. However, compared with traditional vaccines, the immune response stimulated by DNA vaccines is relatively weak, which is not enough to cause sufficient immune protection, especially for humans and large animals. Therefore, studying the mechanism of action and influencing factors of DNA vaccines is crucial for the development and application of the vaccine.
The mechanism of action of DNA vaccine
Current studies have shown that the immune response induced by DNA vaccines includes both humoral immunity (specific antibodies) and cellular immune responses with longer memory times and cell killing power. It is generally considered that after the nucleic acid vaccine is introduced into the body, it is taken up by surrounding tissue cells, antigen-presenting cells or other inflammatory cells. The plasmid DNA molecules taken up by tissue cells such as muscle cells are then transcribed into mRNA in the nucleus and then transferred to the cytoplasm for translation into antigenic protein molecules. An antigenic protein molecule secreting cells released into the interstitial space is captured by an antigen-presenting cell, processed into an antigen peptide, and presented to the T cell to initiate an immune response. APCs in peripheral lymphoid organs directly ingest nucleic acid vaccines, express antigens and present them to T cells, triggering an immune response. Dendritic cells are the most important antigen-presenting cells in the process of nucleic acid immunization, while B cells do not participate in antigen presentation during nucleic acid immunization. After eliciting an immune response, the cytotoxic T cell response recognizes and kills the muscle cells expressing the foreign antigen, causing the myocyte to dissolve and release the intracellular antigen, and APC directly acquires the antigen from the injection site, and then initiates the subsequent immune response. The combined action of several pathways allows DNA vaccines to stimulate T lymphocytes via the histocompatibility complex MHC I and MHC II pathways, as well as activate B lymphocytes. Tissue cells such as muscle cells may play a role in storing plasmids and releasing them during the immunization process.
DNA vaccines are a relatively new development in the field of vaccinology, and this approach is now moving toward rational DNA vaccine design. Strategies include optimizing vector backbones, transgenic sequences, co-expression stimuli, introduction systems for vectors, and targeting vectors for obtaining appropriate immunostimulation. Another consideration is the use of design methods to optimize gene expression. Since been discovered, DNA vaccine has entered a new stage after more than 10 years of development. Due to its ease of use and wide application, it has become a trend in the development of new vaccines in the 21st century. Although the DNA vaccine itself is relatively less immunogenic, recent studies have shown that DNA vaccines are primed, enhanced with recombinant viral vectors or recombinant protein vaccines, and are extremely effective in activating the immune system and inducing a strong immune response. This prime-boost immunization program has been used as a new vaccine model. The effects of DNA vaccines are determined by factors such as the plasmid itself, vaccine adjuvants, and immunization protocols, and their interactions. There are many strategies for enhancing the immunological or therapeutic effects of DNA vaccines, including optimization of antigen expression, selection of immune pathways, delivery vehicles, and selection of adjuvants.