We have all heard of the Covid-19 vaccines and we hope that the end to Covid-19 is in reach - but how do these vaccines work and will we really return to 'normality'?
There are now two vaccines being administered in the UK: the Pfizer/BioNTech vaccine and The University of Oxford / AstraZeneca vaccine. One other vaccine, the Moderna vaccine, was approved by the MHRA (Medicines and Healthcare products Regulatory Authority) at the end of December, and will be available in the spring.
To understand how these vaccines work, you need to know a little about viruses.
Viruses are basically made up of a protein coat with a genetic core and they can only replicate inside other cells, they cannot replicate by themselves - this is one of several reasons why viruses are usually not regarded as living (and as they are not living in the first place - we cannot kill viruses!). The SARS Cov-2 virus causes the disease Covid-19 so the purpose of the vaccines is to prime our immune system against this virus. All 3 vaccines target the SARS Cov-2 spike protein, which is on the outside of the protein coat of the virus, and essential to it for entering the body cells and replicating. To get into our body cells the spike protein on the outside of the virus binds to protein receptors on host cells, called ACE-2 receptors. SARS Cov-2 has a single strand of RNA (the genetic code) inside it's protein coat and when it enters the host cell this RNA is released and then replicated by the host cell (the body cell). The RNA is then used by the host cell to produce structural proteins which are then assembled into viral particles which are then released from the host cell as more SARS Cov-2.
At present you do not have a choice which vaccine you will receive, but what is the difference between them and what does it mean to us individually and as a population, both in the UK and worldwide?
First of all the similarities:
The purpose of vaccines is to stimulate the immune system to recognise antigens (foreign proteins) and to rapidly bring about an immune response to the antigen and destroy it before it can cause the person to become unwell. As I said earlier, all 3 vaccines attack the spike protein to stop it getting into our body cells. They do this by introducing nucleic acids (which carry the genetic code for the spike protein) into the body. These nucleotides are taken up by special white blood cells (cells of the immune system) called dendritic cells. Dendritic cells are usually found under the skin and around muscle cells so the injection in the arm muscle means the nucleotides are introduced near these cells. When the dendritic cells take up the nucleotides they enter the cytoplasm, the fluid part of the cell which contains the organelles (the 'workhouses' of the cell). One type of organelle, the ribosomes, act as microscopic protein factories - they decipher the code on the nuclei acid called messenger RNA and produce the specific piece of the spike protein that it codes for. There are millions of ribosomes in a cell so the spike protein (which is the antigen to bring about the immune response) is mass produced. The dendritic cells then display these pieces of spike protein on their cell membranes (the outer layer of the cell) and move towards the lymph nodes where there are a multitude of different white blood cells (cells of the immune system). This then triggers production of T cells (special white blood cells) which destroy the virus particles and they also release interferon (a messaging chemical) to stimulate other cells of the immune system, the B cells, to respond. B cells then produce antibodies (specific proteins) which bind onto the virus and help with its destruction. Memory T and B cells are also produced which will then recognise the antigen if it enters the body again, and so a swift response will occur and hopefully this will prevent the recipient of the vaccine from succombing to Covid-19.
Now the differences:
The Pfizer/BioNTech vaccine is based on mRNA technology. Pfizer is an American pharmaceutical firm and BioNTech is a German biotechnology company. The vaccine needs to be kept at -70°C long term but can be kept at 2-8°C for 5 days for distribution purposes. It is administered as 2 injections (to the muscle in the upper arm), 21 days apart and it does not contain eggs, preservatives, peanuts or latex. It does contain polyethylene glycol (PEG) which is in a group of known allergens commonly found in medicines, so if allergic to this the Oxford/AstraZeneca vaccine can be administered instead. It's efficacy (how effective it is in controlled clinical trials) is 95%. This number was calculated in trials by looking at the number of people who caught Covid-19 out of all the 21,720 people who were given the vaccine and the 21,728 people who were given the placebo. 9 caught Covid-19 in the vaccinated group and 169 people caught Covid in the placebo group. It is not known why those who had been vaccinated caught Covid-19.
How does it work? The Pfizer/BioNTech and Moderna vaccines are the first vaccines to use mRNA to generate an immunological response to a pathogenic microorganism. mRNA stands for messenger ribonucleic acid which is basically a 'photocopy' of the code on a gene that codes for a particualr protein. The mRNA in the vaccine carries the code for essential parts of the spike protein so will pass the code onto any cell that it enters. Administering the vaccine involves injecting saline solution containing lipid nanoparticles (a minute fatty sphere) containing artificial copies of parts of the mRNA. When the nanoparticles are injected they are taken up by the dendritic cells of the immune system and hence the mRNA carrying the spike protein code enters the cell. The mRNA code can then be read by the ribosomes to make the piece of spike protein.
Protective immunity builds up within 4 weeks of the first dose but we do not know how long immunity lasts as the second dose of the vaccine was only administered in trials 5 months ago. It is expected that the worst case scenario is that yearly boosters will be necessary. News released this week says there is scientific evidence that most people who have tested positive for Covid-19 have at least 5 months of immunity although some people can catch Covid-19 twice.
Can vaccinated people still transmit the virus? It is not known as the trials were only designed to investigate how effective the vaccine was against symptomatic Covid-19 cases and confirmed SARS-Cov-2 infections. Further studies on transmission are apparently being carried out by Pfizer.
The University of Oxford / AstraZeneca vaccine is a chimpanzee adenovirus vaccine vector. AstraZeneca is a British-Swedish pharmaceutical and biopharmaceutical company with HQ in Cambridge. The vaccine can be kept in a normal fridge (2-8°C), which makes it easier to distribute than the Pfizer/BioNTech vaccine. It is administered as 2 injections (to the muscle in the upper arm), 4-12 weeks apart and it does not contain eggs, preservatives, peanuts or latex. It also does not contain polyethylene glycol (PEG), unlike the Pfizer/BioNTech vaccine. The vaccine's efficacy is 70.4%, calculated from two different dose regimens. If administered at a half dose and then at full dose it's efficacy is 90% (3 in 1367 people caught Covid-19 in the vaccinated group compared to 30 in 1374 in the placebo group) and if administered in two full doses it has an efficacy of 62% (27 in 4440 caught Covid-19 in the vaccinated group compared to 71 in 4455 people who received the placebo). The MRHA, however, only approved the use of 2 full doses as there was not enough data from the half and then full dose regimen, so this vaccine only has an efficacy of 62%.
How does it work? The vaccine is made up of an attenuated (weakened and harmless) adenovirus that causes a common cold in chimpanzees and due to it being genetically altered it cannot replicate inside the human body cells. This type of technology is not new and it is proven to generate a strong immune response when used in other vaccines. The genetic code for the SARS Cov-2 spike protein is carried by the chimpanzee adenovirus (hence why the adenovirus is called a vector vaccine). When the adenovirus enters the host cell the piece of SARS Cov-2 RNA is also taken up. The RNA code is then transcribed (or 'photocopied') to make the corresponding mRNA and the code is then translated by the ribosomes to make the piece of spike protein, just like with the Pfizer/BioNTech vaccine, to bring about the immune response as described above.
We know that vaccines do not work for everyone. Others have weaker immune responses to the vaccine, for various different reasons, some of which are unknown but some because of underlying medical conditions such as being immunosuppressed. So is there a way to check that it has stimulated our immune system enough to protect us from SARS Cov-2? Could we use antibody tests? Antibody tests could potentially be used to monitor response to vaccination but there are several problematic factors. If you are infected by Covid-19 you produce 2 types of antibody - one against the the protein that encapsulates the RNA and a neutralising antibody that targets the spike protein. The current vaccines only stimulate the immune system to produce the neutralising antibody against the spike protein. The common antibody test that is used to see if you have been infected by SARS Cov-2 only detect the antibody against the protein that encapsulates the RNA and they do not detect the neutralising antibody and so they will not show whether the vaccine has worked. Some quantitative antibody tests (ones that show both whether the antibody is present and at what levels) have been developed can help evaluate the response of the immune system to a vaccination but presently are only approved for research and clinical trials. These quantitative antibody tests are commonly used, such as to develop the 'flu vaccine each year because there is no time to do human trials . Every year a new 'flu vaccine needs to be developed so researchers check whether the new vaccine triggers the immune system to produce enough 'flu antibodies by using the quantitative antibody test. So the answer is at present you cannot get a test to make sure you are immune to Covid-19 after you have been vaccinated but this could change in the future as more antibody tests are developed and more is understood about SARS Cov-2.
Once we have had the vaccine can we go about life as we used to know it before Covid? Well the straight answer at the moment is no, if we want to work together to protect the whole population. First of all you need to make sure you wait at least a week after the second injection to allow your immune system to respond properly to protect you. Secondly, we still do not know whether the people who have been vaccinated can still transmit the virus or catch Covid asymptomatically - we still need more data on transmission. There are some people out there that, due to underlying medical conditions, canot have the vaccine, and we need to protect them. To protect the population we have to get number of viral particles right down and as long as there are unprotected body cells out there, the virus will reproduce and make more viral particles. We still need to take care, keep out distance, wear face masks, wash our hands and generally be sensible. If you want to go off to a cottage with some friends, who have all been vaccinated, who do not have underlying health problems, and who do not have unvaccinated relatives at home that they live with then that should be OK. However, as soon as you are out in public wear a mask to prevent infection (you are not 100% protected and we still don't know whether the vaccine prevents asymptomatic infection), and hence transmission.
The important thing is that we all work towards herd immunity, which, even with the present immunisation programme, could take another year. Herd immunity (or population immunity) is achieved when most of the population is immune to a disease (either through vaccination or becoming immune due to previous infection) and it is important as it provides indirect protection to those that are not immune, such as those who cannot have the vaccine for underlying medical reasons. If 80% of people are immune it means 8 out of 10 people will not be infected if they come into contact with someone who has Covid-19, and the virus is less likely to be spread. This means that infection rates will drop and the more vulnerable people who are not immune are being better protected. The percent of the population that need to become immune to a diseases to achieve herd immunity depends on how contagious a disease is. Measles require 95% of the population to be immune to achieve herd immunity whilst polio only requires 80%. We do not know the percentage required to provide herd immunity to Covid-19, and it will vary depending on population, the vaccine used, and other variations between areas, but it has been estimated to be 70-80%. However, this number can only be increasing as the mutations lead to more infective variants of SARS-Cov-2. So basically we are looking at carrying on the the face mask wearing, social distancing and hand washing until a large proportion of the population is vaccinated. However, there may be regional relaxation of rules before this, if we look at how things have gone so far through this pandemic, but as soon as you travel to other regions the restrictions would need to be followed again. There is no doubt the reaching of herd immunity will rely on people being sensible. Getting vaccinated and rushing off abroad and not following restrictions will most likely stretch that finishing line further away. I watch the progress of these variants with interest - at the moment they do not think that the mutation is having a significant impact on the effectiveness of the vaccines, but this may change. If this happens it does not mean we are back to square one as it is easier to alter a vaccine than make one from scratch (see the 'flu vaccine) but it will put us back. If we all fly off to all corners of the world this increases the risk of introducing variants to the country. We want to reach herd immunity internationally, and for that to happen we have to help each other. The distribution of vaccines is not equal across all countries and the quality of the vaccines in some countries is not really known as some vaccines have been administered with trials of only small numbers of people, or without finishing trials. This competition to be 'the first' or 'the best' is not healthy in my mind - we need to look at this as a global problem, like the Covax Facility. Covax is a global collaboration, involving more than two-thirds of the world, and its aim is to ensure all countries will be able to access the vaccine, no matter what their economic situation. Unless we cooperate and help, this pandemic is going to be a problem for longer than it needs to be.
If, after further research it is found that the vaccine has a significant effect in lowering transmission of SARS-Cov-2 then maybe the world will open up to us and we will return to normality....although what will the 'new normal' be like?
