28 Jan What are the types of vaccines
The immune system recognizes antigens expressed on the surface or inside the pathogen (the microorganism that causes the disease) as foreign antigens. All vaccines work by stimulating an immune response to a specific pathogen or part of the pathogen that causes the disease. In case of later contact with the pathogen, the cells of the immune system, memory B and T lymphocytes, recognize and efficiently remove or destroy the pathogen and thus protect the organism from infection.
Vaccines trigger B lymphocyte activation and promote a humoral immune response with the production of neutralizing antibodies. T cell lymphocyte-mediated cellular immune response is also crucial for protection against infections and immunopathology associated with severe infections.
The ideal vaccine should result in a robust CD4+ and CD8+ T cell response, as well as in a high titer of neutralizing antibodies.
Vaccines are medical preparations that contain attenuated live or dead pathogens or just a fragment, or genetic codes of pathogen antigens that stimulate the body’s immune response. Newer vaccines contain genetic codes (DNA or messenger RNA) of the pathogen antigen, and antigen synthesis takes place in the cells of the vaccinated person. There are several approaches in making vaccines and the ingredients of vaccines vary depending on the production process and the nature of the antigen.
Some of the diseases we can protect ourselves from with vaccines are smallpox, mumps, rubella, diphtheria, polio, whooping cough and others. COVID-19 vaccines are now in use.
There are several types of vaccines and they are:
1. Whole Pathogen Vaccines
The oldest and most well-known method of vaccination is the use of the whole pathogen that causes the disease in the vaccine in order to obtain an immune response similar to that during a natural infection. The use of pathogens in a vaccine would cause an active disease and could potentially be dangerous for a person receiving it with the risk of spreading the disease to other people. Modern vaccines do not use the entire pathogen, but pathogens that have been modified.
2. Live attenuated (attenuated) vaccines
Live attenuated vaccines contain whole bacteria or viruses that are “weakened” (attenuated) and they trigger a strong protective and lasting immune response similar to a natural infection, but do not cause disease in healthy people. In most modern vaccines, the “weakening” of the pathogen is achieved by certain genetic and other modifications in the laboratory.
However, live vaccines are not suitable for people whose immune system does not work properly, either due to treatment with certain drugs (immunosuppressive drugs) or due to the existence of certain diseases (immunodeficiency).
Examples of live attenuated vaccines are:
Examples of live attenuated vaccines are:
- Rotavirus vaccine
- MMR vaccine (smallpox, mumps and rubella vaccine)
- Tuberculosis vaccine (BCG vaccine)
- Herpes zoster vaccine
- The varicella vaccine
- Yellow fever vaccine
- Oral typhus vaccine (non-injectable vaccine)
3. Inactivated vaccines
Inactivated vaccines contain whole bacteria or viruses which have been killed or have been altered, so they cannot replicate. Inactivated (dead) vaccines are produced from whole or parts of bacteria or viruses that are inactivated by heat or chemicals (formalin and others). Inactivated vaccines do not contain live bacteria or viruses and can be given to people with a weakened immune system.
However, inactivated vaccines do not always create a strong or long-lasting immune response as live attenuated vaccines, and a higher number of doses needs to be given to achieve the expected protection against infectious disease. They also need to contain an adjuvant. Adjuvants are substances that help the immune response to the vaccine to be stronger and longer lasting. As a result, common local reactions may be more noticeable and frequent with these types of vaccines.
Subunit vaccines do not contain whole bacteria or viruses, but contain one or more specific pathogen antigens.
Examples of inactivated vaccines:
- Whooping cough vaccine (wP vaccine)
- Vaccine against polio (IPV vaccine)
- Hepatitis A vaccine
- Rabies vaccine
4. Recombinant vaccines
Recombinant vaccines are made using bacterial cells or yeast cells. Some of the DNA taken from a virus or bacterium is inserted into the cells that produce a given protein. For example, in order to make a vaccine against hepatitis B, part of the DNA from the hepatitis B virus is inserted into the DNA of yeast cells. Yeast cells then produce one of the surface proteins of the hepatitis B virus, which is purified and used as the active ingredient in the vaccine.
Examples of recombinant vaccines:
- Hepatitis B vaccine
- HPV vaccine (human papilloma virus)
- MenB vaccine. It contains recombinant proteins from the surface of meningococcal bacteria.
5. Toxoid vaccines
Some bacteria release toxins, harmful proteins, and the goal is to achieve protection against toxins with the vaccine, and not against the bacteria itself. The immune system recognizes bacterial toxins in the same way as it recognizes other antigens on the surface of bacteria and is able to trigger an immune response to them. Some vaccines are made with inactivated versions of these toxins, “toxoids” that are not harmful, but trigger a strong immune response.
- Diphtheria vaccine
- Tetanus vaccine
- Pertussis (whooping cough) vaccine – contains pertussis toxoid, along with proteins from the surface of pertussis bacteria
6. Conjugate vaccines
“Conjugated” means “connected” or “joined”. In order to achieve protection against some bacteria, the immune system needs to recognize and react to polysaccharides (complex sugars on the surface of bacteria), and not to proteins. Studies have shown that a strong immune response is achieved when a polysaccharide is bound (conjugated) to a protein.
In most conjugate vaccines, the polysaccharide is bound to the diphtheria protein or tetanus toxoid.
Examples of conjugate vaccines:
- Hib vaccine (Haemophilus influenzae type b) containing a polysaccharide linked to tetanus toxoid
- MenC vaccine (in Hib / MenC vaccine), which contains a polysaccharide linked to tetanus toxoid
- PCV (pediatric pneumococcal vaccine), which contains polysaccharides from the surface of 13 species of bacteria associated with diphtheria toxoid (CRM197)
- MenACVI, which contains polysaccharides from the surface of four types of bacteria that cause meningococcal disease associated with diphtheria or tetanus toxoid
7. Virus-like particles (VLP) vaccines
Virus-like particles (VLPs) are molecules that closely resemble viruses but are non-infectious because they do not contain viral genetic material. They can exist naturally or individual viral structural proteins are synthesized and then form a virus-like structure. In a VLP vaccine, they may be viral structural proteins themselves or, alternatively, VLPs may be produced to display antigens of another pathogen or even multiple pathogens on the surface. VLPs are effective in stimulating the immune response. In some cases, VLP structural proteins may act as adjuvants, enhancing the immune response to the target antigen.
Examples of VLP vaccines:
- Hepatitis B vaccine.
- HPV vaccine (human papilloma virus)
8. OMV (Outer Membrane Vesicles) vaccines
Bacteria naturally produce outer membrane vesicles (OMV) that are basically a bleb of the outer cell membrane of bacteria. OMVs contain many antigens that are found on the cell membrane. OMV is a non-infectious particle. In the laboratory, OMVs can be used to make vaccines. OMVs can also be modified to remove toxic antigens and preserve antigens suitable for stimulating the immune response. OMVs also act as adjuvants. This is a newer vaccine technology, an example of a licensed vaccine is:
- MenB vaccine (meningococcal B vaccine)
9. Nucleic acid vaccines
Nucleic acid vaccines work differently from other vaccines because they do not contain pathogen antigens. Instead, these vaccines contain a genetic code (DNA or mRNA) that allows the synthesis of the target protein of the pathogen in the cells of the person being vaccinated. Nucleic acid-based vaccines are rapidly and easily developed and are thought to be increasingly used in the future.
RNA vaccines use mRNA (messenger RNA) that is encapsulated in a lipid nanoparticle. The lipid envelope protects mRNA from enzymatic degradation, and also provides entry into the cell by binding to the cell membrane. The mRNA then binds to the ribosomes in the cytoplasm of the cells where the target antigen protein is transcribed and synthesized. mRNA remains in the cytoplasm of the cell for several days and is degraded and removed. The synthesized target protein is taken up by the antigen presenting the cells and both the humoral and cellular immune response is triggered. The mRNA in the vaccine does not enter the nucleus and is not incorporated into the genetic material.
The Pfizer BioNTech and Modern COVID-19 vaccines are iRNA vaccines.
DNA is more stable than mRNA and is usually given by the electroporation technique to allow cells to take the DNA vaccine. The introduced DNA of the target antigen is translated into mRNA, and then the target proteins that stimulate the immune response are synthesized.
There are currently no licensed DNA vaccines, but there are many in development.
Viral vectored vaccines
Viral vector vaccines are a newer technology, which uses harmless viruses to deliver the genetic code (DNA) of target antigens to cells, which then produce protein antigens that stimulate the immune response. Viral vector vaccines are grown in cell lines and can be developed quickly and easily on a large scale. Viral vector vaccines are in most cases significantly cheaper to produce compared to nucleic acid vaccines.
- Replicating viral vector vaccines contain harmless viruses that replicate, so that replicating viral vectors retain the ability to create new viral particles. The advantage of these vaccines is that the replicating virus provides a continuous source of antigen over a longer period of time compared to non-replicating vector vaccines, thus triggering a stronger and longer-lasting protective immune response. Replicating viral vectors are harmless and cannot cause disease.
A vector Ebola vaccine called Hervebo (rVSV-ZEBOV) uses a vesicular stomatitis virus. The vaccine was approved across Europe for use in 2019 and has been used in several Ebola epidemics to protect over 90,000 people. The vaccine is primarily used in “ring vaccination”, where close contacts of an infected person are vaccinated to prevent the spread of the virus.
- Non-replicating vector vaccines contain harmless viruses that do not replicate but only deliver the DNA of target antigens to the cells. They have the advantage because the vaccine cannot cause the disease and the side effects associated with the replication of viral vectors are reduced. However, the antigen is produced only as long as the initial vaccine remains in the cells (several days). The immune response to these vaccines is generally weaker than that of replicating viral vectors and therefore more doses need to be given.
The Oxford-AstraZeneca vector vaccine against COVID-19 uses a virus that does not replicate as ChAdOk1. The Sputnik V vaccine against COVID-19 contains two types of adenovirus as a vector.
If you have questions, comments and suggestions for topics I will be happy to answer.
- Ahmed SS, Ellis RW, Rappuoli R. Technologies for making new vaccines. In: Plotkin S, Orenstein W, Offit P, Edwards K, editors. Plotkin’s Vaccines. 7th ed. Philadelphia: Elsevier; 2018. p. 1283-304.
- Callaway E. The race for coronavirus vaccines: A graphical guide. Nature. 2020;580(7805):576-7.
- Oxford Vaccine Group – https://www.ovg.ox.ac.uk/