Nucleic acid vaccine is to clone an exogenous gene encoding a specific antigen into an eukaryotic expression plasmid, and then inoculate the recombinant plasmid into the body, so that the exogenous gene can be expressed in the host body, producing an antigen to stimulate the immune system and induce specific immune response. Nucleic acid vaccine is the third generation vaccine after inactivated vaccine, Viral Vaccine and recombinant protein vaccine.
In May 1994, the World Health Organization (WHO) Global Vaccine and Immunoregulation and other three agencies jointly held a conference on nucleic acid vaccines in Geneva. The participants fully affirmed the potential application value of nucleic acid vaccines. Nucleic acid vaccines have many prominent advantages:
(1) they can express natural protein antigens, form correct folding and post-translational glycosylation modifications, what is called the vaccine delivery and present them to the host immune system similar to the natural infection process, closer to the natural molecular form, including configuration-related sites, so that they can induce more effective immune response.
(2) It can induce omnidirectional immunity, including cellular immunity and humoral immunity. After immunization with nucleic acid vaccine, specific antibodies with high titers and CTL reaction can be detected.
(3) Production is simple, cost is low, stability is good and storage is convenient. Nucleic acid vaccine only involves gene operation. It does not need radiation protection facilities like the first generation attenuated live vaccine, nor does it need cell culture, protein purification and other complex processes like the second generation Recombinant Protein Vaccine. The nucleic acid vaccine is only a gene fragment of an antigen of the pathogen, not the gene of the whole pathogen, and the plasmid is used as a vector, and no infectious factors are involved. Immunization is sustained and long-term immunity can be obtained by one vaccination, which avoids the tedious need to strengthen immunization for many times, such as inactivated vaccine and recombinant subunit vaccine.
The cross-protection of homologous and heterologous strains, using conservative DNA sequences between homologous and different strains as nucleic acid vaccine, can break through the limitation of geographical strains, which has been confirmed in influenza A virus. Therefore, nucleic acid vaccines have shown great potential in the prevention of infectious diseases such as bacteria, viruses and parasites. It has been proved that DNA vaccine has both safety of recombinant subunit vaccine and high efficacy of attenuated live vaccine in inducing comprehensive immune response. The research of nucleic acid vaccine is becoming a new direction of development.
In 1990, Wolff. first proposed the technique of naked DNA. They tried to make mouse muscle cells absorb plasmid DNA to produce new proteins by chemical methods. The control group was injected with DNA without any chemical reagents. Unexpectedly, the muscle cells of the control group absorbed the exposed plasmid DNA and expressed exogenous proteins at a high level. Williams found that the protein expressed in vivo could induce immune response in 1991. Tang confirmed Williams’discovery in 1992. In 1993, Ulmer confirmed that the recombinant plasmid encoding influenza A virus nucleoprotein could effectively protect mice against different subtypes of influenza virus. Subsequently, a large number of animal experiments showed that under suitable conditions, DNA vaccination can produce both cellular and humoral immunity.
At present, there are two expression vectors, plasmid DNA and RNA. Using RNA as vaccine can solve some safety problems related to DNA vaccine. Because of the short existence time of the RNA, it will not integrate into the chromosomal DNA, so it will not cause insertion mutation. It has been proved that direct injection of RNA into mouse skeletal muscle results in transient expression of reported genes in vivo. Martinod injected the NP gene encapsulated by liposome directly into the body subcutaneously and intravenously, effectively stimulated the specific cytotoxic T cell effect of anti-virus, and the NP protein produced by the translation of the RNA could be processed into different antigenic polypeptides according to the corresponding MHC type I molecule. It should be emphasized that RNA cannot replace DNA vaccine, it does not have all the advantages of DNA.
Its expression is short and does not induce long-term immunity. Inorganic adjuvant will play a important role in this access. In addition, RNA is not as stable as DNA, and its production, storage and transportation costs are higher than DNA. Plasmid DNA is more commonly used because of its stable nature, easy extraction and preservation, long expression time in vivo and strong immune response. Unlike inactivated vaccines, attenuated live vaccines and recombinant genetic engineering vaccines, the chemical properties of commonly used nucleic acid vaccines are double-stranded cyclic DNA.
Although the occurrence and development of nucleic acid vaccine is not long, it has made many gratifying achievements. It has many advantages, such as simple operation, high level of protective humoral and cellular immunity induced by the organism at the same time, and is safe and effective. It has broad application prospects in anti-pathogenic infections and anti-cancer. It is attracting strong interest of scholars in various fields. However, in the development of nucleic acid vaccines, some potential problems cannot be ignored. There are still many imperfections in the development of nucleic acid vaccines. There is still a lot of work to be done in practical application.