Types of vaccine

 

Vaccines can be divided into a number of different types, but ultimately work on the same principle. This is to stimulate the immune response to recognise a pathogen (a disease-causing organism) or part of a pathogen. Once the immune system has been trained to recognise this, if the body is later exposed to the pathogen, it will be removed from the body. Specifically, the immune system recognises foreign ‘antigens’, parts of the pathogen on the surface or inside the pathogen, that are not normally found in the body.

 

Whole Pathogen Vaccines 

The oldest and most well-known method of vaccination is to use the whole disease-causing pathogen in a vaccine to produce an immune response similar to that seen during natural infection. Using the pathogen in its natural state would cause active disease and could potentially be dangerous to the individual receiving it and risk the disease spreading to others. To avoid this, modern vaccines use pathogens that have been altered. 

Live attenuated Vaccines

Live attenuated vaccines contain whole bacteria or viruses which have been “weakened”(attenuated) so that they create a protective immune response but do not cause disease in healthy people. For most modern vaccines this “weakening” is achieved through genetic modification of the pathogen either as a naturally occurring phenomenon or as a modification specifically introduced by scientists.

Live vaccines tend to create a strong and lasting immune response and include some of our best vaccines. However, live vaccines may not suitable for people whose immune system doesn’t work, either due to drug treatment or underlying illness. This is because the weakened viruses or bacteria could in some cases multiply too much and might cause disease in these people. 

Live attenuated vaccines used in the UK schedule:

Live travel vaccines used in the UK:

  • Yellow fever vaccine
  • Oral typhoid vaccine (not the injected vaccine)

Inactivated Vaccines

Inactivated vaccines contain whole bacteria or viruses which have been killed or have been altered, so that they cannot replicate. Because inactivated vaccines do not contain any live bacteria or viruses, they cannot cause the diseases against which they protect, even in people with severely weakened immune systems. However, inactivated vaccines do not always create such a strong or long-lasting immune response as live attenuated vaccines. 

‘Whole killed’ vaccines used in the UK schedule:

Examples of ‘whole killed’ travel vaccines used in the UK:

  • Rabies vaccine
  • Japanese encephalitis vaccine

 

Subunit Vaccines

Most of the vaccines in the UK schedule are subunit vaccines which do not contain any whole bacteria or viruses at all. Instead, these vaccines typically contain one or more specific antigens (or “flags”) from the surface of the pathogen. The advantage of subunit vaccines over whole pathogen vaccines is that the immune response can focus on recognising a small number of antigen targets (“flags”). 

Subunit vaccines do not always create such a strong or long-lasting immune response as live attenuated vaccines. They usually require repeated doses initially and subsequent booster doses in subsequent years. Adjuvants are often added to subunit vaccines. These are substances which help to strengthen and lengthen the immune response to the vaccine. As a result, common local reactions (such as a sore arm) may be more noticeable and frequent with these types of vaccines. 

Recombinant Protein Vaccines

Recombinant vaccines are made using bacterial or yeast cells to manufacture the vaccine. A small piece of DNA is taken from the virus or bacterium against which we want to protect and inserted into the manufacturing cells. For example, to make the hepatitis B vaccine, part of the DNA from the hepatitis B virus is inserted into the DNA of yeast cells. These yeast cells are then able to produce one of the surface proteins from the hepatitis B virus, and this is purified and used as the active ingredient in the vaccine. 

Most of the vaccines in the UK schedule are subunit vaccines which do not contain any whole bacteria or viruses at all. (‘Acellular’ means ‘not containing any whole cells’.) Instead these kind of vaccines contain polysaccharides (sugars) or proteins from the surface of bacteria or viruses. These polysaccharides or proteins are the parts that our immune system recognises as ‘foreign’, and they are referred to as antigens. Even though the vaccine might only contain a few out of the thousands of proteins in a bacterium, they are enough in themselves to trigger an immune response which can protect against the disease.

Recombinant vaccines used in the UK schedule:

Toxoid Vaccines

Some bacteria release toxins (poisonous proteins) when they attack the body, and it is the toxins rather than the bacteria itself that we want to be protected against. The immune system recognises these toxins in the same way that it recognises other antigens on the surface of the bacteria, and is able to mount an immune response to them. Some vaccines are made with inactivated versions of these toxins. They are called ‘toxoids’ because they look like toxins but are not poisonous. They trigger a strong immune response.  

Toxoid vaccines used in the UK schedule:

Conjugate Vaccines

‘Conjugate’ means ‘connected’ or ‘joined’. With some bacteria, to get protection from a vaccine you need to train the immune system to respond to polysaccharides (complex sugars on the surface of bacteria) rather than proteins.  But in the early days of polysaccharide vaccines it was found that they did not work well in babies and young children.

Researchers discovered that they worked much better if the polysaccharide was attached (conjugated) to something else that creates a strong immune response. In most conjugate vaccines, the polysaccharide is attached to diphtheria or tetanus toxoid protein (see ‘Toxoid vaccines’ above). The immune system recognises these proteins very easily and this helps to generate a stronger immune response to the polysaccharide. 

On product information sheets the diphtheria toxoid is often called ‘CRM197 carrier protein’, because it is almost the same as diphtheria toxoid but not quite.  

Conjugate vaccines used in the UK schedule:

  • Hib vaccine (in the 6-in-1 vaccine and Hib/MenC vaccine), which contains a polysaccharide joined to tetanus toxoid
  • MenC vaccine (in the Hib/MenC vaccine), which contains a polysaccharide joined to tetanus toxoid
  • PCV (children’s pneumococcal vaccine), which contains polysaccharides from the surface of 13 types of the bacteria which causes pneumococcal disease joined to diphtheria toxoid (CRM197)
  • MenACWY, which contains polysaccharides from the surface of four types of the bacteria which causes meningococcal disease joined to diphtheria or tetanus toxoid

There is also a conjugate vaccine for Typhoid fever, called Typhoid Conjugate Vaccine (TCV). This vaccine was shown to be effective in a study led by Oxford Vaccine Group, and is recommended by WHO to protect children from Typhoid fever in endemic regions such as Nepal and Bangladesh.  

Virus Like Particles

Virus-like particles (VLPs) are molecules that closely resemble viruses, but are non-infectious because they contain no viral genetic material. They can be naturally occurring or synthesized through the individual expression of viral structural proteins, which can then self-assemble into the virus-like structure. In some cases, the antigens in a VLP vaccine are the viral structural proteins themselves. Alternatively, the VLPs can be manufactured to present antigens from another pathogen on the surface, or even multiple pathogens at once. As each VLP has multiple copies of an antigen on its surface it is more effective at stimulating an immune response that a single copy. In some cases, the structural proteins of the VLP can act as adjuvants, helping to strengthen the immune response to the primary target antigen. 

A handful of VLP-based vaccines are currently used worldwide: 

OMV Vaccines

Outer Membrane Vesicles (OMVs) are naturally produced by bacteria and are essentially a bleb of the bacterial outer cell membrane. This contains many of the antigens found on the cell membrane but is a non-infectious particle. In the lab these OMVs can be harvested from bacteria to use as vaccines. The OMVs can also be modified so that toxic antigens are removed and antigens suitable for stimulating an immune response can be kept. OMVs also naturally act as adjuvants. This is a newer vaccine technology so there are few licenced examples:

 

Nucleic Acid Vaccines

Ever wondered what happens inside your cells when you are infected with a virus? Or how the new COVID-19 vaccines work? The answer to these questions can be found in how our cells receive instructions to make proteins. Actually, our cells are a bit like factories...

 

 

Credit: Concept & Script by Dr Sean Elias. Design by Ben Leighton. Developed in collaboration with Typhoidland (Dr Samantha Vanderslott) and The Vaccine Knowledge Project (Dr Tonia Thomas). Voiceover: Tom Wilkinson and Music: Long Way Home by Spinning Ratio.

 

Nucleic acid vaccines work in a different way to other vaccines in that they do not supply the protein antigen to the body. Instead they provide the genetic instructions of the antigen to cells in the body and in turn the cells produce the antigen, which stimulates an immune response. Nucleic acid vaccines are quick and easy to develop, and provide significant promise for the development of vaccines in the future.

RNA vaccines

RNA vaccines use mRNA (messenger RNA) inside a lipid (fat) membrane. This fatty cover both protects the mRNA when it first enters the body, and also helps it to get inside cells by fusing with the cell membrane. Once the mRNA is inside the cell, machinery inside the cell translates it into the antigen protein. This mRNA typically lasts a few days, but in that time sufficient antigen is made to stimulate an immune response. It is then naturally broken down and removed by the body. RNA vaccines are not capable of combining with the human genetic code (DNA). 

There are two RNA vaccines authorised for emergency use in the UK at present. The Pfizer BioNTech and the Moderna COVID-19 vaccines are both RNA vaccines. 

DNA vaccines

DNA is more stable than mRNA so doesn’t require the same initial protection. DNA vaccines are typically administered along with a technique called electroporation. This uses low level electronic waves to allow the bodies’ cells to take up the DNA vaccine. DNA must be translated to mRNA within the cell nucleus before it can subsequently be translated to protein antigens which stimulate an immune response.

There are currently no licenced DNA vaccines, but there are many in development.

 

Viral Vectored Vaccines

As with nucleic acid vaccines, viral vectored vaccines are a newer technology, using harmless viruses to deliver the genetic code of target vaccine antigens to cells of the body, so that they can produce protein antigens to stimulate an immune response. Viral vectored vaccines are grown in cell lines and can be developed quickly and easily on a large scale. Viral vectored vaccines are significantly cheaper to produce in most cases compared to nucleic acid vaccines and many subunit vaccines. 

Replicating 

Replicating viral vectors retain the ability to make new viral particles alongside delivering the vaccine antigen when used as a vaccine delivery platform. As with live attenuated whole pathogen vaccines this has the inherent advantage as a replicating virus that it can provide a continuous source of vaccine antigen over an extended period of time compared to non-replicating vaccines, and so is likely to produce a stronger immune response. A single vaccine may be enough to give protection. 

Replicating viral vectors are typically selected so that the viruses themselves are harmless, or are attenuated, so whilst they are infecting the host, they cannot cause disease. Despite this, as there is still viral replication going on there is an increased chance of mild adverse events (reactions) with these vaccines.

A vaccine to prevent Ebola called Ervebo (rVSV-ZEBOV) uses a recombinant vesicular stomatitis virus. This vaccine was approved across Europe for use in 2019, and has been used in multiple Ebola outbreaks to protect over 90,000 people. The vaccine has primarily been used in “ring vaccination”, where the close contacts of an infected person are vaccinated to prevent the virus from spreading.

Non-replicating

Non-replicating viral vectors do not retain the ability to make new viral particles during the process of delivering the vaccine antigen to the cell. This is because key viral genes that enable the virus to replicate have been removed in the lab. This has the advantage that the vaccine cannot cause disease and adverse events associated with viral vector replication are reduced. However, vaccine antigen can only be produced as long as the initial vaccine remains in infected cells (a few days). This means the immune response is generally weaker than with replicating viral vectors and booster doses are likely to be required.

A viral vectored vaccine developed to prevent Ebola was licensed for use by the European Medicines Agency in July 2020. The Oxford-AstraZeneca COVID-19 vaccine which was approved for emergency use by the MHRA in December 2020, also uses a non-replicating viral vector called ChAdOx1. 

This diagram shows how the Oxford-AstraZeneca COVID-19 vaccine works:

 

Page last updated: 
Friday, April 30, 2021