Some related terms:

Antibody:

A protein molecule that can be found in the blood and is intended to attack
bacteria, viruses and transplanted organs.

Antigen:

Any substance that causes your immune system to produce antibodies against it.

A molecule that stimulates an immune response by activating leukocytes (white

blood cells) that fight disease. Antigens may be present on invaders, such as
bacteria, viruses, parasites, fungi, and transplanted organs, or on abnormal cells,
such as cancer cells.

Pathogen:

A bacterium, virus, or other microorganism that can cause disease.

Vaccines:

A substance used to stimulate the production of antibodies and provide immunity

against one or several diseases, prepared from the causative agent of a disease,
its products, or a synthetic substitute, treated to act as an antigen without
inducing the disease.

Immunity:
Immunity is the ability of the body to defend itself from 'foreign bodies'. This
means rejecting infections, clearing up dust which gets in the lungs, and killing
cancer cells. Immunity is of two types. Innate immunity protects the host against
infection, but has no 'memory', and so gives no long-term immunity.

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 recognize a pathogen (a disease-
causing organism) or part of a pathogen.
Once the immune system has been trained to recognize this, if the body is later exposed to
the pathogen, it will be removed from the body. Specifically, the immune system recognizes
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.

Examples of Live attenuated vaccines used in the UK schedule:

● Rotavirus vaccine
● MMR vaccine
● Nasal flu vaccine
● Shingles vaccine
● Chickenpox vaccine (special groups only)
● BCG vaccine against TB (special groups only)
● Covid 19 (Sinovac)
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:

● Inactivated polio vaccine or IPV (in the 6-in-1 vaccine, pre-school booster, teenage
booster and pertussis vaccine in pregnancy)
● Some inactivated flu vaccines which are described as ‘split virion’
● Hepatitis A vaccine (special groups only)
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:

● Hepatitis B vaccine (in the 6-in-1 vaccine and as the separate hepatitis B vaccine)
● HPV vaccine
● MenB vaccine. This contains proteins from the surface of meningococcal bacteria.
Three of the proteins are made using recombinant technology.

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:

● Diphtheria vaccine (in the 6-in-1 vaccine, pre-school booster, teenage booster and
pertussis vaccine in pregnancy)
● Tetanus vaccine (in the 6-in-1 vaccine, pre-school booster, teenage booster and
pertussis vaccine in pregnancy)
● Pertussis (whooping cough) vaccine (in the 6-in-1 vaccine, pre-school booster and
pertussis vaccine in pregnancy). This contains pertussis toxoid, together with
proteins from the surface of the pertussis bacteria. It is often called an ‘acellular’
vaccine.

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:

● Hepatitis B vaccine
● HPV vaccine

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:

● MenB vaccine (meningococcal B vaccine)

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.

Example: Pfizer-BioNTech, Moderna for Covid 19

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.

Example:

Johnson & Johnson’s Janssen COVID-19 Vaccine

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.

Example:

Oxford-AstraZeneca, Sputnik V (Gamaleya Research Institute)

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

The four types of COVID-19

vaccine – a snapshot
There are four main types of vaccines currently approved, in
approval or being considered in the MENA region in its fight
against COVID-19.
By Rachel McArthurJanuary 21, 202104:03 AM

Credit: Shannon Stapleton/Getty Images

Over the past month, a number of COVID-19 vaccines have been approved for general
or emergency use in the Middle East and North Africa (MENA). Understandably, there
remains confusion over which one to choose – for example, should it be based on
technology? On which one has the most advantages? Or simply on the one a country’s
government chooses?

We’re not here to tell you which type of vaccine to choose - that is, and should be, your
own choice. However, what we can agree on is that all vaccines work by exposing the
human body to particles or molecules that trigger an immune response, thus protecting
the subject from future infection. The key difference between the four main types of
vaccines is the method of exposure used.

Here are the key differences.

1) WHOLE VIRUS VACCINE

Vaccines include: Sinopharm, Sinovac

Number of doses required: 2 doses, intramuscular

Other licensed vaccines that use this type of technology: Hepatitis A, polio, rabies
(all inactivated type)

What to know: The whole virus vaccine uses a weakened or deactivated form of the
pathogen that causes COVID-19 to trigger protective immunity to it.

The two vaccines mentioned above – Sinopharm and Sinovac – both use inactivated
pathogens, therefore they cannot infect cells and replicate, but can trigger an immune
response.

Benefits: According to Gavi, the Vaccine Alliance (GAVI), the advantages of an

inactivated whole virus vaccine include the fact its technology is well established, it is
suitable for people with compromised immune systems, and it’s relatively simple to
manufacture.

Challenges: Booster shots may be required.

2) RNA or mRNA VACCINE

Vaccines include: Pfizer-BioNTech, Moderna

Number of doses required: 2 doses, intramuscular

Other licensed vaccines that use this type of technology: None

What to know: Since no other existing licensed or approved vaccine uses this type of
technology, the Messenger RNA (mRNA) variety could be mistaken for something
completely new to healthcare. However, a number of mRNA vaccines have been
studied in the past for illnesses and diseases including cytomegalovirus (CMV),
influenza, rabies, and the Zika virus.

According to the Centers for Disease Control and Prevention (CDC): “Researchers have
been studying and working with mRNA vaccines for decades. Interest has grown in
these vaccines because they can be developed in a laboratory using readily available
materials. This means the process can be standardised and scaled up, making vaccine
development faster than traditional methods of making vaccines.”

So how does it reportedly work? The COVID-19 RNA vaccine consists of mRNA
molecules made in a lab that code for parts of the SARS-CoV-2 virus – specifically the
virus’ spike protein.

Once injected into the body, the mRNA instructs the cells to produce antigens – such as
the spike protein mentioned – which are then detected by immune cells, triggering a
response by the body’s lymphocytes.

The killer T-cells destroy the infected cells, while the B-cells and helper T-cells support
antibody production. Whoever is exposed to the COVID-19 coronavirus in the future
would have an immune system that recognises it, and in turn fight off the infection.

Benefits: According to the University of Cambridge’s PHG Foundation, advantages

include good safety (since there are no live components, there’s no risk of the vaccine
triggering disease), reliability, and that it’s relatively simple to manufacture.

Challenges: Disadvantages include unintended effects (such as an unintended immune

reaction), ensuring effective delivery into the body (since free RNA in the body is quickly
broken down), storage issues, plus the fact that this type of vaccine has never
previously been licensed for humans.

3) NON-REPLICATING VIRAL VECTOR

Vaccines include: Oxford-AstraZeneca, Sputnik V (Gamaleya Research Institute)

Number of doses required: 2 doses, intramuscular

Other licensed vaccines that use this type of technology: Ebola

What to know: This type of vaccine introduces a safe, modified version of the virus –
known as “the vector” – to deliver genetic code for the antigen. In a COVID-19 vaccine,
the “vector” is the spike proteins found on the surface of the coronavirus.

Once the body’s cells are “infected”, the cells are instructed to produce a large amount
of antigens, which in turn trigger an immune response.

Benefits: Viral vector-based vaccination is another well-established technology that can

trigger a strong immune response as it also involves both B cells and T cells.

Challenges: Previous exposure to the vector could reduce effectiveness, plus these
types of vaccines are relatively complex to manufacture compared to others.

4) PROTEIN SUBUNIT

Vaccines include: Novavax

Number of doses required: 2 doses, intramuscular

Other licensed vaccines that use this type of technology: Hepatitis B,

meningococcal disease, pneumococcal disease, shingles

What to know: The protein subunit vaccine contains purified “pieces” of a pathogen
rather than the whole pathogen to trigger an immune response. It is thought that by
restricting the immune system to the whole pathogen, the risk of side effects is
minimised.

Benefits: The protein subunit vaccination is also a well-established technology that’s

advantageous for those with compromised immune systems.
Challenges: This type of vaccine is relatively complex to manufacture, and adjuvants
and booster shots may be required.

Editor’s note: Information is accurate at time of publishing; however, given the ongoing
updates in research – plus possible changes in governmental decisions – the
availability and reliability of these vaccines is subject to change at any time.