What We Do Know

What We Don't Know


In this article we are going to explore how humans can become protected from infectious diseases. We will compare  natural immunity (e.g. through infection) with the immunity provided by traditional vaccines and with the way the new COVID-19 vaccines create immunity.  

Our Immune System

The human body is a wonderful creation and an amazing feat of engineering capable of dealing with most things life can throw at it. One of the most amazing aspects is the human immune system. It has been dealing with colds, flus, bacterial infections, viruses and other allergens for millennia –  long before the modern pharmaceutical industry was born.

As our scientific understanding of the human body advances, we increasingly know that much of what makes up our immune system is in our gut, and that most of it isn’t human at all but rather a thriving ecosystem of flora and fauna bacteria – now called the gut biome. 

So feeding and caring for that bacterial ecosystem is a key factor in our overall ability to fight disease. That flies in the face of much of our modern thinking – where bacteria are seen as bad and something to be eradicated with chemicals and antibiotics as quickly as possible. Has our drive to have everything uber-clean actually made us less able to fight diseases naturally?

Natural Immunity

Natural immunity can be considered to be what we have or develop simply by being alive and interacting with our environment.

It is made up of two aspects – innate immunity and acquired immunity.

Innate Immunity – is what we are born with. Our bodies, rather than having the ability to deal with specific germs or pathogens, have instead a range of broad responses to help prevent infection by stopping viruses and bacteria in their tracks or quickly eliminating them from the body as soon as they are detected.  These include:

  • the cough reflex
  • the sneeze reflex
  • the vomit reflex
  • mucus formation
  • skin and its enzymes

Without needing to know anything more that “this doesn’t belong here” our body is already well equipped to prevent a lot of diseases and illnesses.

Acquired Immunity – is what our bodies learn as they go through life by being exposed to all manner of bacteria, viruses and other foreign invaders. Some of it comes from having a disease and learning how to defeat the pathogen causing it. Some of it comes from simply playing in the mud as children and being exposed to a tiny amount of a substance that gets tackled before it even gets chance to make us ill.

Natural Infection v Traditional Vaccines v COVID-19 Experimental Gene Vaccines

Now let’s take a look at how immunity to COVID-19 would be created by each of the three methods – natural infection, a traditional vaccine (which we don’t currently have in the UK) and the new experimental gene vaccines (which are completely new types of vaccines never tried on humans before). 

Natural Infection Immunity

Natural infection occurs when you are exposed to a “foreign” organism, bacteria, virus, or allergen. With a respiratory virus such as the one that causes COVID-19, this is most likely to occur through breathing in airborne virus particles. If the virus particles manage to get around the first line of defence – your innate immunity (e.g. not all are expelled by coughing or sneezing) – then your body’s secondary defences start to take action. 

There has been much in the media about the COVID-19 “spike protein”, however viruses are made up of many different proteins, many of them common to many different viruses. Your immune system may recognise some of those proteins from previous infections it has dealt with and already know the “recipe” to create antibodies that will attack those virus proteins. If it doesn’t, your immune system figures out what antibodies it needs to make then adapts existing recipes or creates new ones to deal with each of the proteins and stop the virus replicating, bringing the infection to an end.

Your immune system then remembers those recipes for the future so that even if a virus mutates, there’s still a very good chance it will be recognised and dealt with by your immune system.

Having a COVID-19 infection gives your body the chance to learn to recognise the whole virus and all the proteins it is made of. Your immune system remembers how to make a range of antibodies, creating an arsenal of weapons that can target lots of different parts of the virus so you are well armed to deal with future infections of the same or a similar virus.

Traditional Vaccine Immunity

In a traditional vaccine (e.g. polio, smallpox or meningococcal disease) an inactive (“dead”) or attenuated (weakened) version of the foreign organism, such as a virus, is injected into you. Your body produces an activated cellular response, some of these cells producing lots of antibodies to fight against the weakened virus. You may get a mild version of the disease and then you recover or you may not get any symptoms at all.

As with natural infection immunity, your immune system learns to recognise the whole of the injected organism and remembers the recipe for the various antibodies needed to tackle all the different aspects of the virus.

If you come into contact with the virus again (either the original or a different variant) your  immune system will recognise it and start to produce the appropriate antibodies, allowing you to fight off the virus.

However, in some instances, once a virus is inactive or weakened it may not appear harmful enough to trigger an immune response or the immune system may not bother committing the antibody recipe to long term memory. So vaccine manufacturers have to add an adjuvant (an additional ingredient in the vaccine) to force the body to mount a proper immune response to the vaccine or regular boosters are required to trigger another immune response.

When it comes to COVID-19, no-one has yet succeeded in completing the development of a viable attenuated virus vaccine due to problems producing or weakening the virus. The only inactive virus based vaccines for COVID-19 have been developed in China and are not available in the UK. 

Experimental Gene Vaccines

The brand new DNA and mRNA vaccines currently undergoing a mass rollout in the UK use novel platforms (vaccine technology) that have never been used on humans before.

Rather than injecting a live but weakened or an inactive virus for your immune system to respond to, they work by getting your own cells to produce the spike protein that the COVID-19 vaccine has in order to trigger an immune response. This is achieved in one of two ways.

DNA - deoxyribonucleic acid - based vaccines

These vaccines use an animal virus (one that doesn’t cause disease in humans) that has been genetically modified to include the DNA code for the instructions on how to produce the COVID-19 spike protein.

When the animal virus enters the human cell it passes on the DNA instructions to the human cell which then starts to produce the COVID-19 spike protein.

The immune system recognises the spike protein as foreign and produces an antibody to attack it.

mRNA - messenger ribonucleic acid - based vaccines

mRNA gene vaccines are created in a laboratory and are purely synthetic.

Naked, unprotected mRNA is very unstable and is quickly degraded by enzymes within the environment. In order to protect it from degradation and help uptake into the cell, the mRNA is encapsulated within a lipid-nanoparticle (LNP).

The mRNA delivers the instructions to the human cell to start producing the COVID-19 spike protein.

As with the DNA based vaccines, hopefully the immune system recognises the spike protein as a pathogen and mounts an immune response by creating a suitable antibody. 

The downside of both these approaches is that unlike natural infection and a traditional vaccine, your immune system is only learning how to recognise and combat the COVID-19 spike protein. It is not being shown the full virus particle and is therefore only developing one weapon to attack one part of the virus. Your ability to recognise and combat a future COVID-19 infection is very limited.

How Long Does COVID-19 Vaccine Immunity Last?

There is evidence of waning of protection over time, most notably among older adults. There is not yet enough follow-up data to properly assess waning.

There are some considerations with respect to how long immunity lasts for both DNA Viral Vector and mRNA vaccines:

  1. The strength of the antigen of the spike protein produced by our bodies compared to the strength of the spike protein on the virus – if this is weaker in our bodies, then the antibody response will be sub-optimal and may not last for very long.
  2. The possibility that the spike protein produce by our bodies after vaccination varies chemically from the original viral spike protein – again, the antibody response would be sub-optimal and less effective.
  3. Because of the way the mRNA vaccines work, i.e. getting into our cells and instructing them to make spike protein, the making of spike protein may only last for 1 cell cycle. When the cell dies, new cells that replace it don’t have the code for the spike protein manufacture – meaning lower production of antibody for a limited time period.

This means that unlike natural immunity and most traditional vaccines, protection from COVID-19 by these new experimental vaccines is likely to need to be topped up regularly for the rest of the person’s life. Only time will tell whether this is annually, six-monthly or even more frequently.

The COVID-19 Vaccines in More Detail

DNA Viral Vector Vaccines

AstraZeneca (UK brand name Vaxzevria)

This is a new viral vector type of vaccine. It was developed at Oxford University in collaboration with AstraZeneca.

It has never been used in humans before and there is no long-term human medical data. Thus, the long-term side effects are not yet known.

What is it?

ChAdOx1 nCOV-19 is a chimpanzee adenovirus with the full length SARS-CoV-2 spike protein inserted. In other words, a chimpanzee virus that does not affect humans has been genetically modified to add the DNA sequence of the COVID-19 spike protein.

The virus is then grown in genetically modified human embryonic kidney cells.

After injection the virus enters the human cells and passes on the DNA code for the spike protein.  The human cells then start to produce the spike protein which should then trigger an immune response.

How Effective Is It?

According to the Week 42 surveillance report from Astra Zeneca, after 2 doses, observed vaccine effectiveness against symptomatic disease with the Delta variant reaches approximately 65 to 70%

Reported Side Effects
  • Skin disorders & long term inflammatory skin conditions including Pityriasis rubra pilaris
  • Blood Clots & Blood disorders including Vaccine Induced Thrombotic Thrombocytopenia.
  • Facial paralysis including Bells Palsy
  • Guillain Barre Syndrome

Janssen/Johnson & Johnson

Unlike the other COVID-19  vaccines, the J&J vaccine platform has been used before in humans, though there is still only limited data available on long term effects.

It was used to develop an Ebola vaccine which was rolled out in the Democratic Republic of Congo between 2016 & 2020.

What is it?

Ad26.COV2-S is a human adenovirus (from the same family of viruses as the common cold) that has been made incapable of replication and then genetically modified to add the DNA sequence of the COVID-19 spike protein.

The inactivated Ad26 adenovirus passes on the spike protein DNA sequence to the human cells it encounters. The human cells then start to produce the spike protein which should then trigger an immune response.

Johnson & Johnson are now using this same AD26 adenovirus approach to develop vaccines for HIV, RSV & Zika.

How Effective Is It?

According to the World Health Organisation, the J & J vaccine is 66.9% effective. This means that recipients of this vaccine still have a 1 in 3 chance of developing COVID-19 if exposed to the virus.

Reported Side Effects
  • Anaphylaxis
  • Thrombosis with thrombocytopenia syndrome
  • Capillary Leak Syndrome
  • Guillain Barre Syndrome

mRNA Vaccines

Pfizer/BioNTech (Brand name Comirnaty)

This vaccine uses mRNA technology which has never been used in humans before.

The vaccine is a joint venture between pharma giant Pfizer and German cancer and infectious disease therapy developers BioNTech. 

What is it?

BNT162b2 is a synthetic mRNA strand containing the instructions for the production of the SARS-CoV-2 spike protein encapsulated in a lipid nanoparticle (a tiny fat wrapper) to prevent it being broken down by the human body before it gets chance to enter a cell. 

Once the mRNA is delivered into the cell, the cell’s DNA interprets the instructions and starts to produce and display the COVID-19 spike protein on the outer surface of the cell which is then targeted by the immune system.

How Effective Is It?

After 2 doses, observed vaccine effectiveness against symptomatic disease with the Delta variant reaches approximately 80 to 95%

Reported Side Effects
  • Myocarditis (heart inflammation)
  • Pericarditis (inflammation of the membrane surrounding the heart)
  • Blood Clots & Blood disorders including Prothrombotic Immune Thrombocytopenia
  • Facial paralysis including Bells Palsy
  • Guillain Barre Syndrome

Moderna (Brand name Spikevax)

This vaccine uses brand new mRNA vaccine technology so again there is no long term safety data available. 

It is a joint venture between Moderna and the US National Institute of Health and is the first vaccine product that Moderna has brought to market.

What is it?

mRNA-1273 is a synthetic mRNA strand containing the instructions for the production of the SARS-CoV-2 spike protein encapsulated in a lipid nanoparticle (a tiny fat wrapper) to prevent it being broken down by the human body before it gets chance to enter a cell. 

Once the mRNA is delivered into the cell, the cell’s DNA interprets the instructions and starts to produce and display the COVID-19 spike protein on the outer surface of the cell which is then targeted by the immune system.

How Effective Is It?

The World Health Organisation states that based on data provided by Moderna the vaccines is shown to be 94.1% effective. 

Reported Side Effects
  • Myocarditis & Pericarditis
  • Blood Clots & Blood disorders including Vaccine Induced Thrombotic Thrombocytopenia. 
  • Anaphylaxis

Flawed Assumption?

An assumption that appears to have been made by all the vaccine developers is that each and every person who receives the DNA or mRNA vaccine, will make exactly the same spike protein and hence their bodies will make exactly the same antibodies. This is a flawed assumption for a very complex, fluid and dynamic biological system (i.e. us).

This is now starting to be demonstrated as researchers in Germany have discovered that some people make an abnormal spike protein on receiving the AstraZeneca vaccine. This abnormal spike protein complexes with activated platelets (cell components which aid clotting) and the body produces antibodies to this complex leading to thrombocytopenia and clotting.


We hope this article has given you a better understanding of both your own immune system and how the new COVID-19 vaccines differ greatly from traditional, well establised vaccines.

So when friends, family, work colleagues and the government say “it’s just a jab” in an attempt to cajole or coerce you into having it, and brush off any concerns or hesitancy you may have, you are now better able to explain to them that these are unlike any other vaccines that you or they may have had. 

All the vaccines only have temporary authorisation to deal with the COVID-19 emergency. They are all still in clinical trials and their long term effects – both positive and negative – will only come to light as time passes. You may feel it is safer to wait until the trials are completed.

Undergoing any medical treatment (with the exception of donating blood, bone marrow or an organ) is a decision for you to make based on your own body, your own health and medical history  – and for your benefit alone. You should not be feeling pressured or obliged to undergo any medical treatment to protect other people.

If you have any concerns about having a COVID-19 vaccine or having a booster, please seek medical advice then weigh up your own personal risk profile from both COVID-19 and the vaccines.


We would like to thank the following people for their assistance in producing this article:

“JoeSquared” – PhD Molecular Biologist, ex-employee of Public Health England, Pfizer and AstraZeneca – for creating the Natural Infection/Traditional Vaccine/COVID-19 Experimental Gene Vaccines Infographic.

Dr Mark Belkin PhD BAppSc (LabMed) – retired chief scientist immunology and haematology (private pathology) – for ensuring that in simplifying the science we didn’t accidentally introduce any misinformation.

Essential Context for Understanding this report

These reports contain a complete listing of all suspected adverse reactions that have been reported to the MHRA via the Yellow Card scheme for COVID-19 vaccines. This includes all reports received from healthcare professionals, members of the public, and pharmaceutical companies.

This information does not represent an overview of the potential side effects associated with the vaccines. A list of the recognised adverse effects of the COVID-19 vaccines is provided in the information for healthcare professionals and the recipient information here. Conclusions on the safety and risks of the vaccines cannot be made on the data shown in the report alone. When viewing the report, you should remember that:

  • Reporters are asked to submit Yellow Card reports even if they only have a suspicion that the vaccine may have caused the adverse reaction. The existence of an adverse reaction report does not necessarily mean that the vaccine has caused the reaction.

  • It may be difficult to tell the difference between something that has occurred naturally and an adverse reaction. Sometimes reactions can be part of the condition being treated rather than being caused by the vaccine.

  • Many factors have to be considered when assessing whether a vaccine has caused a reported adverse reaction. When monitoring the safety of medicines and vaccines, MHRA staff carry out careful analysis of these factors.

  • It is not possible to compare the safety of different vaccines by comparing the numbers presented in the vaccine reports. Reporting rates can be influenced by many factors including the seriousness of the adverse reactions, their ease of recognition and the extent of use of a particular vaccine. Reporting can also be stimulated by promotion and publicity about a product.

For a vaccine to be considered safe, the expected benefits will be greater than the risk of having harmful reactions. It is important to note that most people receive vaccinations without having any serious side effects.

Risks and benefits of medicines

For a medicine to be considered safe, the expected benefits of the medicine will be greater than the risk of suffering harmful reactions. It is important to note that most people take medicines without suffering any serious side effects.

All medicines can cause reactions. The patient information leaflet accompanying the medicine, or available from your pharmacist, lists the known side effects associated with the medicine. Healthcare professionals such as doctors and pharmacists can also provide this information. Information on side effects of medicines can be found on the NHS website.

Monitoring the safety of medicines and vaccines

Information collected through the Yellow Card scheme is an important tool in helping the MHRA and CHM monitor the safety of medicines. Yellow Card reports of suspected adverse reactions are evaluated, together with additional sources of evidence such as worldwide literature, in order to identify previously unidentified hazards or side effects.

If a new side effect is identified, information is carefully considered in context of the overall side effect profile for the medicine or vaccine, and how it compares with other medicines used to treat the same condition.

The MHRA will take action, if necessary, to ensure that the product is used in a way that minimises risk, while maximising patient benefit. Such changes may include, for example, restricting the indication, or special warnings and precautions. Rarely, a drug may need to be withdrawn from the market if the risk of side effects is considered to outweigh the benefits of treatment. Please see our How we monitor the safety of medicines section for further information.

Use of Yellow Card data for publication

If you wish to copy or circulate the information contained within a report to anyone else, please ensure that a copy of these guidelines is also provided.

The MHRA and CHM encourage the use of data from the Yellow Card scheme in research and for publication, but wish to ensure that the limitations of interpretation of the data are made clear.

If you propose to publish information based on Yellow Card data, the MHRA is most willing to provide advice on how the Yellow Card information might be best used and presented. The MHRA is also willing to provide feedback on manuscripts prior to publication. Please write to the Deputy Director, Safety and Surveillance Group by email.