RTL Today reader Dr Angela Marley (PhD, Immunology & Infectious Disease) lays out the basics on vaccines, and how to decide on vaccination.

The question you are likely asking yourself now is: Is the Covid-19 vaccine safe and what is the difference between the various types? To help you see through some of the complexity, this article will take you through the basics of what vaccines are, how they work and what the difference between various Covid-19 vaccine types are including results from the clinical trials.

What are vaccines?

Vaccination protects you against harmful diseases before you come into contact with them by using your body’s own natural defences to build resistance to specific infections. To build immunity against a specific pathogen (e.g. viruses or bacteria), the vaccine needs to hold the right key. This key comes in the form of harmless proteins called ‘antigens’: parts of the pathogen not normally found in our body. The antigen is recognized by the cells as something foreign, which activates an immune response and creates immunological memory. A vaccine also contains substances called ‘adjuvants’ to help boost the immune response, which increases efficacy. Finally, preservatives and stabilizers are added to the vaccine to ensure it stays effective and protected during storage and transportation.

Vaccine ingredients can look unfamiliar, but many of the components used in vaccines occur naturally in the body, in the environment, and in food. All of the ingredients in vaccines – as well as the vaccines themselves - are thoroughly tested and monitored to ensure they are safe before the vaccine is approved for use in the general population.

How do vaccines work?

The term vaccine comes from the Latin word for cow, reflecting the origins of the first ever vaccine that was created – the small pox vaccine. Small pox was one of the most devastating diseases known to humanity, but also goes down in history as the first disease eradicated through vaccination. In 1796, it was discovered that immunization with cow pox (hence the link to the Latin ‘vacca’) caused comparatively mild disease and importantly immunity against the deadly small pox virus. This underlines the basic concept of vaccinations. Vaccines show your immune system specific information about a virus or bacteria to activate an immune response and associated immunological memory.

Vaccines tend to create a strong and long lasting immunity because they are based on the natural mechanisms used by viruses or bacteria. For example, during natural infection viruses get into the cell and insert genetic information (DNA or RNA). Cells use DNA and RNA to produce proteins; DNA is used to create RNA, which is then used to create protein. So by inserting genetic information, the virus essentially hijacks the cell’s own machinery to produce the viral proteins necessary to create copies of itself. The immune system recognizes these viral proteins as foreign antigens, which activates a response to fight the infection. An immune response including antibody production takes a few days to respond the first time. Vaccines give the immune system a head start, teaching your body to recognize the pathogen by mimicking parts of natural infection but without actually causing disease.

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The first small pox vaccine was cow pox, a live infectious virus very similar to small pox. This similarity was enough to educate the immune system to recognize the small pox virus without causing serious disease. However, vaccines today typically either contain only part of the pathogen (i.e. the antigen) or the genetic information for antigen production in the cell.

How are vaccines different, and what are the different Covid-19 vaccine types?

All vaccines aim to show the immune system a small noninfectious part of a virus or bacteria (the antigen) to activate an immune response and create immunological memory. Notably, some vaccines don’t contain the antigen itself, but rather the genetic instructions for your cells to produce the antigen. For example, the Measles, Mumps & Rubella (MMR) and the flu vaccines are attenuated vaccines containing genetic information for protein production. Such attenuated vaccines use a weakened virus as a vector (typically an altered version of the common cold virus) that is stripped of any disease-causing genes and sometimes also genes that enable them to replicate. The now harmless vector carries DNA or RNA needed for the production of noninfectious proteins specific to the disease (e.g. MMR or flu) in the cell. The immune system recognizes this protein as foreign, activating an immune response and building memory. Numerous attenuated vaccines are being developed for Covid-19 infections, including the AstraZeneca one already approved for use in the EU/EEA.

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The AstraZeneca vaccine (AZD1222) developed by Oxford University for Covid-19 uses a weakened viral vector that is unable to replicate containing DNA for the SARS-CoV-2 virus spike protein. This means administration of the AstraZeneca vaccine gives cells the instructions to produce the noninfectious SARS-COV-2 virus spike protein, which is then recognized by the immune response as foreign. This leads to immunological memory for the spike protein preparing the body for natural infection with Covid-19, in which case a much faster specific adaptive immune response (including antibody production) prevents the development of disease. The Covid-19 vaccine in development by Johnson & Johnson is also based on the attenuated virus vaccine model. It has been reported that the Johnson & Johnson vaccine may only require 1 dose, which would make the roll out process much simpler.

The search for the Covid-19 vaccine has also led to a new type of vaccine, the mRNA vaccine. Simply, the cell uses DNA to create mRNA, which acts as a messenger for protein production. In fact, mRNA stands for ‘messenger’ Ribonucleic Acid. So where the AstraZeneca vaccine uses DNA to instruct cells to produce mRNA ultimately leading to protein production, the mRNA vaccines from Pfizer-BioNTech and Moderna skip the DNA step. In an mRNA vaccine the mRNA is delivered into the cells to produce noninfectious protein directly. And instead of using a viral vector, mRNA vaccines hold the genetic instructions (mRNA) in a lipid (fat) capsule. This is why there is excitement in the scientific community, because this is the first time the delivery of intact mRNA into cells has been successful in humans. Some would appropriately say this is “pretty cool”, but they might just be referring to the fact that these vaccines need to be stored at very low temperatures (up to -80°C). mRNA is fragile and freezing is needed to prevent it from falling apart. After injection into a person, the lipid capsule protects the mRNA from degradation and helps it reach the cells where the mRNA strand is used to produce the antigen protein that eventually triggers the desired immune response.

mRNA vaccine technology may be new, but is not unknown. This mechanism has been researched for years with interest increasing over the last decade, because no viral vectors are needed and these vaccines can be produced with readily available materials. This makes vaccine development using mRNA technology faster than traditional methods, potentially speeding up the response time to infectious disease outbreaks. Indeed, vaccine development for the Zika virus using the mRNA technology is also currently in clinical trials.

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Finally, protein sub unit vaccines including the Hepatitis B vaccine contain a small noninfectious part of the pathogen (the antigen) directly for immune activation. Such vaccines are relatively cheap and easy to produce, and more stable than those containing whole viruses or bacteria. However, protein sub unit vaccines are thought to activate a weaker immune response because they do not enter the cell, which is why a booster is often required to increase efficacy. Novavax is currently developing such a protein sub unit vaccine for Covid-19 infection.

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Here is a summary of the Covid-19 vaccines discussed in this text in order of vaccine type

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*European Medicines Agency

Why were Covid-19 clinical trials so quick, and what were the results?

The process of vaccine research and development typically takes 10–15 years before starting manufacturing and distribution. For the Covid-19 vaccine the estimated time-line is 12-18 months. The accelerated timeline for clinical testing of SARS-CoV-2 vaccines has raised some concerns over vaccine safety, with the perception that the process was rushed. However, the global resource allocation and scientific focus for the production of a Covid-19 vaccination is extraordinary and unprecedented, with supporting funds to develop Covid-19 countermeasures reportedly in the trillions of dollars. In fact, new programs (including HHS’ Operation Warp Speed (OWS)) have been created to specifically fund and coordinate the accelerated development, manufacturing and global distribution of SARS-CoV-2 vaccines. Pre-clinical and limited clinical trials of vaccines for the severe acute respiratory syndrome (SARS) outbreak in 2003 and the Middle East respiratory syndrome (MERS) outbreak in 2012, as well as research characterizing new/next-generation vaccine platforms and adjuvants also helped provide a head start in SARS-CoV-2 vaccine development.

SARS-CoV-2 vaccine safety is largely being assessed in human trials. An important goal for Phase III clinical trials has been to ensure study cohorts are large and diverse enough so serious safety concerns are not missed. So far, serious side effects have been rare in people who received the SARS-CoV-2 vaccine during clinical trials. Importantly, the incidence of serious adverse events was similar in the vaccine and the placebo groups, showing that the vaccine did not increase the risk for serious side effects. The efficacy of currently approved vaccines ranges from about 60-95%. An important consideration for clinical trials has also been to assess whether the severity of Covid-19 disease is reduced by the vaccine, making the vaccine valuable even if efficacy for Covid-19 prevention is in the lower ranges. So a vaccine that is 60% effective may be good enough if it also prevents serious complications during Covid-19 infection.

Here is a summary of clinical trial results in for the vaccines approved to date by the European Medicines Agency (EMA):

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To vaccinate, or not to vaccinate, that is the question. 

Ultimately, the efficacy of the vaccine is dependent on the immune response activated by the person receiving the vaccine. This is why clinical trials are necessary to determine the efficacy as well as safety of the vaccine in a large group of people across different ages and various other criteria. Once the vaccine passes the numerous stringent approval processes for mass vaccination in the general population, monitoring of safety and efficacy continues, which means data is continuously updated. How this complex data is then interpreted, translated and communicated by governments and the media can cause confusion, scepticism and anxiety. This can understandably make the decision whether to get vaccinated or not very hard.

According to the European Centre for Disease Control (ECDC) there have been 99,727,853 Covid-19 infections worldwide (18,849,065 in EU/EEA) and 2,137,670 associated deaths worldwide (449,395 in EU EEA). So far around 86.8M vaccine doses have been given (Our world in data), and there have been no official vaccine associated deaths reported to date. That’s not to say that no one has died after receiving the vaccination, but such deaths have been reported to be in line with the expected, all-cause mortality rates and causes of death in a sub-population of people. As such, the data currently suggests that the risks associated with Covid-19 infection vastly outweigh the risks of potential adverse effects of the available vaccinations.

To address any concerns you may have about getting the Covid-19 vaccine, talk to your doctor and ask questions so that you can make an informed decision by considering the risks vs. benefits for your specific situation. Ask your doctor questions like “What do we know about the long-term effects of Covid-19 compared with the vaccine?”, “Do my pre-existing conditions, my age or other criteria make me more susceptible to complications with Covid-19?” and “How do the potential complications with Covid-19 infection compare with potential side effects from the vaccine?”.

The decision is yours, of course, and there are no guarantees. That’s just not how medicine, or indeed science, works. We are all still learning, including scientists, researchers and medical professionals. What we can say is that we have come very far from the first primitive vaccine, the live infectious cow pox that eradicated small pox. What we can say is that Covid-19 has changed our world, and brings very real and proven risks to our lives. We have shown that when the whole world focuses and finances the development of a vaccine, this can be done quickly and efficiently respecting safety procedures. And really, what would the world look like if small pox was still reaping havoc because we had not taken the (arguably much larger) risk hundreds of years ago to immunize people with cow pox?

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Angela Marley, PhD Immunology & Infectious Disease