We have introduced antibiotics before, and its invention makes bacterial infections no longer a fear. However, there is a more terrifying microorganism-virus. Viruses are highly dependent on other living organisms and cannot survive on their own. Once the body is infected, the virus will cause all kinds of harm to the body without any precautions. The emergence of vaccines has provided people with a powerful weapon against the virus. At present, the COVID-19 is still raging around the world, so today we will talk about vaccines and give everyone a popular science about what kinds of vaccines are available.
Vaccines are biological preparations made of bacteria, viruses, toxoids, etc. that can make the body produce specific immunity. The body can gain immunity through vaccination. After the vaccine enters the human body, it can stimulate the human immune system and produce memory B cells. When the pathogen invades the human body again, the B cells can immediately produce antibodies or effector lymphocytes to kill the pathogen, thereby protecting the body. In this way, it is not the vaccine itself that directly kills pathogens, but the antibodies or effector lymphocytes produced by the immune system.
Classification
Attenuated vaccine
The method of artificial cultivation allows bacteria or viruses to produce targeted mutations, thereby greatly reducing pathogenicity. Vaccines made from pathogens with reduced pathogenicity are called attenuated vaccines. Although its virulence is greatly weakened, it still has some reservations without losing its immunogenicity and reproductive ability. After the live attenuated vaccine enters the human body, it is similar to the human body being infected once, except that there will be no serious toxic reaction. During this process, the body’s immune system is activated to produce antibodies and obtain immunity. Attenuated vaccines use live microorganisms, which can act for a long time in the body and induce a strong immune response. Living microorganisms have the characteristic of re-proliferation. In theory, only one vaccination is needed to achieve a satisfactory immune effect. The attenuated vaccines currently in clinical use include: attenuated measles vaccine, attenuated hepatitis A vaccine, freeze-dried attenuated hepatitis A vaccine, freeze-dried attenuated varicella vaccine, attenuated Japanese encephalitis vaccine, attenuated rubella vaccine, attenuated mumps vaccines, oral attenuated polio vaccine, oral attenuated rabies vaccine, etc. However, attenuated vaccines contain live pathogens, and there is a hidden danger of invisible infection. In addition, due to the different pathogenic abilities of pathogens in different live vaccines, live attenuated vaccines have a certain risk of virulence recovery, and the overall safety is not high. Besides, attenuated vaccines are preparations of live microorganisms, which may cause environmental pollution and cross-infection.
Inactivated vaccine
Inactivated vaccines are made from killed bacteria, viruses or Rickettsia. These dead pathogens have completely lost their pathogenicity, but still retain immunogenicity. Inactivated vaccines in clinical use include: inactivated hepatitis A vaccine, influenza vaccine, rabies vaccine and so on. The new coronavirus vaccine developed by Sinopharm Group China Bio-Beijing Company, which has just been launched recently, is an inactivated vaccine. Compared with live attenuated vaccines, inactivated vaccines are safer and will not cause human infection. Inactivated vaccines cannot simulate natural infections and their immunogenicity is relatively insufficient. Therefore, their effect is lower than that of attenuated vaccines, but they can be compensated by increasing the dose and the number of vaccinations (this is why many people are asking why this new coronavirus vaccine needs two injections). Inactivated vaccines often require multiple vaccinations. One dose does not produce protective immunity, but merely “initializes” the immune system. The second or third dose must be vaccinated to produce protective immunity. The immune response it causes is usually humoral immunity, rarely or even no cellular immunity. The antibody titer produced by inactivated vaccines decreases with time. Therefore, some inactivated vaccines require regular booster vaccination. The technical route of inactivated vaccines is mature and the development time is short, that’s why it is so popular.
Subunit vaccine
Genetic engineering subunit vaccine refers to the expression of the target antigen gene in prokaryotic or eukaryotic cells, and the gene product (protein or polypeptide) is used to make a vaccine. For example, the current research on the new coronavirus subunit vaccine based on S protein (S protein is the binding site of SARS-CoV-2 and the ACE2 receptor on human cells, and the S protein is expressed in vitro before it is used to prepare vaccines). Vaccines based on this protein do not need to cultivate the virus, only need to know the gene sequence of the new coronavirus, and then use modern biotechnology to synthesize the S protein. This vaccine retains the antigenicity of the virus without the pathogenicity, does not cause illness due to virus infection, and has good safety. Since proteins expressed in vitro are usually presented by MHC II molecules, protein-based subunit vaccines cannot express antigens in cells like carrier vaccines and then be presented by MHC I molecules to activate T cells to play a killing effect (See “Everyone Learns to Understand Immunology” Issue 15 and “Everyone Learns to Understand Immunology” Issue 16). The more successful genetically engineered subunit vaccine is the hepatitis B surface antigen vaccine.
Recombined vector vaccine
Recombined vector vaccine is to insert antigen gene directly into some non-pathogenic or virulent genes removed microbial genome, and then screen out the individuals who can express antigen normally to prepare vaccine. Such as influenza virus vector vaccine (replicable type) and adenovirus vector vaccine (non-replicable type). Taking the adenovirus vector vaccine as an example, the general operation method is to integrate the target antigen gene into the adenovirus gene. After the vaccination, the virus vector will enter the cells, and the target antigen protein gene inserted into the gene will be transcribed and translated to express the antigen protein. This antigen protein can be directly displayed on the surface of infected cells to trigger cellular immune responses, and it can also be transferred from the inside of the cell to the outside of the cell, thereby triggering the body’s immune response. Adenovirus that cannot replicate itself will be cleared by the body’s immune mechanism, which will not affect the human body and has high safety.
Serum vaccine
This vaccine belongs to passive immunity because it is made directly from specific antibodies and can be divided into three categories. The first type is antitoxin, which is made by immunizing animals (horses or mules) with toxoids to produce antibodies, and then the plasma is separated and purified. The second type is antiserum, which is obtained by immunizing animals with detoxified toxins, bacteria or viruses to produce antibodies, and then the plasma is separated and purified. The third type is specific antibodies, which are antibodies obtained by directly immunizing animals with antigens and then separating and purifying their plasma.
Nucleic acid vaccine
Nucleic acid vaccine is to directly introduce foreign genes (DNA or RNA) encoding a certain antigen protein into animal cells, and synthesize the antigen protein through the expression system of the host cell to induce the host to produce an immune response to the antigen protein, and ultimately achieve the purpose of prevention and treatment of diseases. Nucleic acid vaccines are divided into DNA vaccines and mRNA vaccines.
DNA vaccine is the recombination of antigen gene and expression vector DNA, and then injected into the body. This type of vaccine can synthesize endogenous antigens imitating the infection mode of live viruses, and the endogenous antigens are presented to MHC class I molecules to induce CD8+ T cells to produce killing effects. The preparation of DNA vaccine does not need to obtain the virus, and the research and development institutions can directly manufacture the vaccine according to the gene sequence. However, the disadvantage of DNA vaccine is that the foreign DNA may be integrated with the DNA of the cell itself. Therefore, DNA vaccines especially need to pay attention to safety.
The mRNA vaccine is the same, but it does not need to enter the nucleus to express the antigen. Directly using mRNA as a vaccine, there is no need to enter the nucleus to complete the transcription process, and then translate and express the protein in the cytoplasm like a DNA vaccine. The mRNA vaccine can directly synthesize protein in the cytoplasm, which saves one step compared with the DNA vaccine. The steps of mRNA vaccine are simplified, and there is basically no need to worry about the integration of viral DNA into host DNA. However, mRNA is not as stable as DNA or protein, and its biggest defect is that it is easily degraded. How to ensure that mRNA can enter the host cell smoothly and produce a certain immunogenic protein is a difficult point. For example, the mRNA vaccine developed by Pfizer/BioNTech is at least 94% effective in preventing people from contracting COVID-19.
Peptide vaccine
Peptide vaccine is a vaccine prepared by chemical synthesis technology according to the amino acid sequence of a certain epitope known or predicted in the pathogen antigen gene. Since it is completely synthetic, there is no problem of recovery of virulence or incomplete inactivation. For some antigens that cannot be obtained in a sufficient amount by in vitro culture, peptide vaccines also provide another idea for preparation. Peptide vaccines are currently an important direction of vaccine research, and peptide vaccines for HIV and hepatitis C virus have been developed.