COVID-19 Vaccines: What the Scientific Experts Say
Introduction
The COVID-19 pandemic has impacted greatly on our lives for over a year. There is finally “a light at the end of the tunnel”, with approval of several vaccines. However, a “Misinformation pandemic” has caused confusion. Therefore, I decided it would be helpful to share what I have learnt from attending the following recent online expert scientific panels about the vaccines approved within the UK:
1. The Royal Society[1]: The Race for a Vaccine[2] (28 January 2021).
2. ZOE Symptom Study[3]: COVID-19 Vaccines: What we know so far[4] (3 February 2021).
3. University of Southampton[5]: Beating COVID-19 - Vaccines, Trials and Prevention[6] (9 February 2021).
What are COVID-19 and SARS-CoV-2?
COVID-19 is the disease that develops from exposure to the coronavirus, SARS-CoV-2.
Viruses comprise either ribonucleic acid (RNA) or deoxyribonucleic acid (DNA). COVID-19 is caused by a coronavirus that is RNA based. Coronaviruses are typically respiratory viruses, replicating in the airways. Four coronaviruses circulate yearly, resulting in cold-like symptoms, whereas SARS, MERS and COVID-19 can cause serious illness[2]. SARS-CoV-2 uses its spike proteins (as a key) to enter our cells through ACE-2 receptors (a doorway). It then hijacks our cells’ machinery to replicate and spreads to other cells in our body. COVID-19 develops if there is a high enough viral load within the body.
COVID-19 is a biphasic disease - it has two main phases:
1. Viral replication: Initial illness for about a week, before the patient starts feeling better[2].
2. Inflammatory response: Severity depends upon how successfully the immune system halted viral replication - the lower the viral load, the milder the symptoms[2].
Why vaccinate against COVID-19?
Vaccination programmes are a means to safely attaining herd (community) immunity. They suppress or eliminate the infection by reducing its opportunity to spread. These population-wide initiatives protect everyone by shielding those who have not yet or cannot be vaccinated, as well as protecting the individual[2]. The proportion of the population required to obtain herd immunity depends upon the transmissibility of the specific infection. The higher the R0, the more contagious the infection and the more likely mutations will arise. Therefore, where infections have a high R0, it is important to develop a vaccine to reduce or eradicate disease[6].
Vaccines produce stronger and longer-lasting immunity than naturally acquired immunity from previous infection[2, 6]. Incurring both types of immunity provides a cumulative effect, offering greater protection[6].The vaccines approved so far should prevent hospitalisations and death in most cases[6].
COVID-19 has caused long-lasting problems in some patients’ organs, especially the brain and lungs. The long-term health costs from COVID-19 outweigh any potential vaccine long-term risks[4].
The immune system
The two main parts of the immune system are:
1) Innate immune defence:
This first-line (non-specific) defence is constantly alert for invaders. If a threat is identified, the innate immune system cells search for and kill infected host cells and protect others from infection[7]. In viruses, the lower the viral load, the milder the symptoms. But SARS-CoV-2 suppresses the innate response resulting in an increased viral load[2].
2) Adaptive immune defence:
This secondary response is very specific to the invader (e.g. SARS-CoV-2). The major players are:
· B cells: Antibodies attach to the virus and label it for destruction[7].
· T cells: Kill infected cells, activate other immune cells and support the antibody response[7].
These cells have a subgroup of memory cells tasked with remembering the specific virus and learning to combat it better next time the virus is encountered[7]. It is expected that COVID-19 vaccines should lengthen the immune response to about a year instead of a few months[2, 4, 6].
Types of vaccine
At time of attending the expert panels, vaccines in use within the UK were Pfizer-BioNTech[8] and Oxford-Astra-Zeneca[9] which teach the immune system to target the SARS-CoV-2 spike protein - the key to entering host cells. The immune system recognises the spike protein and uses it to train antibodies and T cells to inactivate this particular protein. With this spike protein inactivated, the virus cannot enter the cell and replicate, rendering it harmless. These vaccines do not contain the actual SARS-CoV-2 virus and, importantly, do not suppress the innate immune response, unlike the virus[2]. Many other COVID-19 vaccines are under development with potential for future use worldwide[2].
The main types of COVID-19 vaccines are:
1. Replication-incompetent vector (Astra-Zeneca, Janssen): An inactivated cold virus producing a spike protein. An immune response is mounted against the spike protein and cold virus[6]. (Used against SARS and MERS[4]).
2. RNA (Pfizer, Moderna): RNA (in this case mRNA or messenger RNA) produces a spike protein from the genetic material carried inside a “lipid particle”. The lipid particle aids the immune response. (Used previously in anti-cancer vaccine research)[6].
3. Recombinant spike protein base (Novavax, Medicago GSK): The spike protein is created in a lab and transported in an “adjuvant” (immune enhancer) to create a stronger immune response. (Fairly traditional method[6].
4. Inactivated virus (Valneva): The virus is grown in a lab, killed and inactivated. This method might be useful against spike protein mutations. (Traditional method)[6].
Efficacy:
Vaccine efficacy (efficiency) percentages indicate the ability of the vaccine to protect against developing COVID-19. It is difficult to compare efficacy between COVID-19 vaccine studies, because researchers use different groups of people and measurements to assess their particular vaccine[4, 6].
Fast vaccine development
Expert scientists were already aware that a viral pandemic posed a serious threat to humanity. Therefore, new vaccine technologies (including mRNA vaccines) had already been in development for many years[2].
At first sight, ten months to develop, test and approve vaccines seems remarkably quick when compared to previous vaccine development. However, this timeframe seems reasonable when it is considered:
· There was huge worldwide government investment (billions of US dollars) - usually there are long delays waiting for funding to trickle through[2].
· The three trial phases ran in parallel - usually they take place one after the other[2].
The World Health Organization was integral in coordinating the development of new COVID-19 treatments and vaccines[10]. The UK’s “Medicines and Healthcare Products Regulatory Agency” (MHRA) is the global expert, previously ensuring vaccine safety for the whole of the European Union. Any uncertainty about vaccine approval is not about safety, it is about how well the vaccines will work and for how long[6].
How vaccines work
1. First dose: Primes the immune system to recognise the SARS-CoV-2 spike protein. Specific antibodies are created, and remembered by memory cells[2]. There is some protection against COVID-19 after two to three weeks (depending on the vaccine)[4]. Partial protection should prevent severe disease, keeping most people out of hospital[2, 4].
2. Second dose: Boosts the immune response, making it stronger and longer lasting. Memory cells recognise the SARS-CoV2 spike protein, produce improved antibodies and memorises them for next time they are needed[2].
12-weeks between vaccine doses
Some were concerned when the advised three weeks gap between vaccine doses was changed to twelve weeks. The timeframe changed after Astra-Zeneca analysed their data from people who had received their second dose at twelve weeks - results indicated better efficacy with a longer gap. They are now analysing data from those who had their second booster later than twelve weeks - the data suggests even higher efficacy[4].
There was no medical reason for Pfizer choosing three weeks between doses - presumably, it was to enable faster turnaround for their vaccine release[6]. It was thought Pfizer vaccines would likely perform comparably to Astra-Zeneca, because they elicit a similar immune response[4].On the 18 February 2021, evidence from Israel’s Pfizer vaccinations reported the second dose could potentially be delayed, because the first dose provides adequate interim protection, but advised more long-term follow-up was needed[11].
Transmissibility
People who have had the vaccine can still carry the virus (SARS-CoV-2) without succumbing to the disease (COVID-19). Hypothetically, it could be spread to someone else, although this is not yet known for sure. But, there is probably reduced risk of transmitting enough virus to cause severe disease, because it cannot replicate as easily in a vaccinated person[2]. The UK’s recent fall in new COVID-19 cases and hospitalisations, suggests the vaccines offer some protection against transmitting the infection to others - we are awaiting further data to confirm whether this is the case.
Vaccine suitability
Questions were raised about whether the vaccine was suitable for all adults:
Previous infection with SARS-CoV-2:
It is likely the first vaccine dose would improve the immune response in those recently infected with the virus (up to six months ago) compared to those who have not been exposed[4]. COVID “long-haulers” should be safe to take the vaccine, because ongoing symptoms are an inflammatory response, not the virus itself[4].
Autoimmune diseases and immune suppressants:
People with autoimmune diseases or prescribed immune suppressants are not usually included in vaccine trials, because they skew the study results, rather than concerns over their safety. Therefore, according to Professor Tim Spector, the vaccines should be safe for this group[4].
Astra-Zeneca and the over 65’s:
Astra-Zeneca was tested on a limited number of over 65’s, because many in this group were advised to shield at the time trials were commencing. Therefore, it seemed inappropriate to ask most of this group to attend research centres[4]. On 15 February 2021, the World Health Organization recommended Astra-Zeneca for adults of all ages based on the available study results[12].
Vaccine side effects
No steps were missed in testing the vaccines before approval[6]. Phase three trials (the biggest phase, testing for efficacy) included ten times more volunteers than usual - sometimes over 30,000 people, compared to the usual 2,000–3,000[2, 6].
The UK’s Joint Committee on Vaccination and Immunisation (JCVI) assessed the Astra-Zeneca vaccine based on millions of doses - their results showed exceptionally good safety. Up to 1,000 reactions are considered normal, but for the Astra-Zeneca trials, there were only the usual immediate minor side effects (e.g. sore arm, fever) and no hospital admissions[6]. Any vaccine side effects of concern are expected to occur fairly immediately; therefore, people usually wait fifteen minutes after vaccination before leaving the vaccination centre[2].
Common side effects:
As with most vaccines, common minor side effects can occur soon after vaccination and may last a few days. The most common is a sore or slightly swollen arm near site of injection. A smaller proportion, experience systemic effects, including headache, fever and/or fatigue. Systemic effects are more likely after the second (booster) dose, because the immune system is already primed to recognise viral proteins[4]. These symptoms indicate the immune system is developing protection. People are more likely to experience side effects if they are anxious about them, even with the placebo saline injection (placebo effect). Symptoms are eased with paracetamol[4].
Side effects due to previous COVID-19 exposure:
Individuals who had previously experienced Covid-19 were twice as likely to experience systemic side effects after the first vaccine. This suggests in these circumstances, the primer (first dose) acts like a booster (second dose), as the immune system was already primed by prior natural exposure to SARS-CoV-2. Consequently, these individuals could have more protection, closer to that experienced after the second dose. It is still safe to have the second booster dose[4].
Mixing vaccines
It has long been known, mixing different classes of vaccines between doses can provide a more efficient immune response[4, 6]. Currently the UK does not plan to mix doses, because this has not been tested on SARS-CoV-2 vaccines yet (this is the next research step)[6]. In the future, a range of vaccine boosters could become available to provide better protection against specific variants[4].
New variants
New SARS-CoV-2 variants were always expected - it is part of natural evolution[2, 4]. Viral replication is not perfect - copying errors result in random mutations. Changes that enable the virus to spread more easily are more likely to become dominant over those that spread slowly, as this increases the virus’s survival chances[2]. Regardless, it is extremely unlikely a variant would completely resist a vaccine- there may be more susceptibility for mild infection, with most avoiding severe illness[6].
If enough people are vaccinated, variant concerns will be less relevant, because the infection will be forced to die out. The key is to work together (worldwide) and focus on vaccination to drive down R0 and levels of virus circulation[4]. With less virus circulating, there is less opportunity for the virus to mutate into new variants.
RNA viruses, such as SARS-CoV-2, evolve slowly. Therefore, it is thought current vaccines should remain effective against COVID-19 for at least a year. Research scientists are working on vaccine tweaks to protect against new variants - a much quicker process than creating vaccines from scratch, as only minor changes to the existing vaccines are required[2, 4, 6]. Also, less volunteers are needed in these trials, further speeding up the process[4].
The Misinformation pandemic
There is major concern about the spread of misinformation by people in a position of trust and those in algorithm-led social media bubbles. The whole of society needs to tackle this issue, including:
· Public citizens/peers,
· Government,
· Scientists[6].
A common misconception by many people is that mRNA vaccines are “gene therapy” and not actually vaccines, because they think the injected mRNA alters human DNA. This does not happen - after the mRNA has passed on its message, it just breaks down and degrades in a harmless manner[6].
The future
It has almost been a year since the UK (and many other countries) first went into lockdown. So what does the future hold for us? This is what the scientific experts predict:
Yearly vaccine boosters:
It is unlikely COVID-19 will completely disappear - instead, it is expected to become a background infection (endemic). We will probably need an annual booster for the immediate future, particularly to protect the vulnerable[4, 6].
Changed behaviour:
There is likely to be an improved attitude towards infection - changing behaviour to prevent infection risk - similar to attitude/behaviour changes towards accidents. Historically, accidents were a common cause of death, but this gradually changed over the years with improved preventative measures[6]. The public are now more aware about the importance of handwashing and ventilation, but other bad habits still need to be addressed, including the UK culture of going into work when unwell[6].
Targeted strategies: Identifying the spreaders:
It is unclear whether spreaders are adults returning home from work, and/or children returning from school. When this has been identified, better targeted health strategies can be introduced to protect the community[2]. Governments are expected to prepare improved response systems to mitigate pandemic spread of emerging future viruses[6].
Utilising technology:
The latest generation vaccines (mRNA and replication-incompetent vector) are as good as, if not better than traditional vaccines. There is very promising potential to use this technology to protect us against other prevalent diseases, including cancer[2].
Future research initiatives:
· Preventing long-haul COVID[6].
· Investigating the impact of the vaccines in long-haul COVID patients[6].
· Research into vaccinating children to protect the community[6].
Lessons learnt:
· The countries suffering least from this pandemic were those with a quick and decisive response: Taiwan learnt from the SARS epidemic in 2003 and reacted quickly. The UK (and other countries) need a quicker and more decisive response the next time an infectious disease emerges[2].
· This pandemic has highlighted some serious inequalities within society needing to be addressed[2].
· Global vaccination is needed to control this pandemic[2].
Returning to ‘normal’
The big question is “Will the Covid-19 vaccines bring back normality?” Currently in the UK, we cannot change our cautious behaviour, because the virus is still widely circulating and we need to protect the whole population[4]. A more normal situation is expected in a year or so, but we need to embrace a new normal to protect humanity. Humans have taken away too much from the planet, affecting the climate and environment- the new normal needs to be a more sustainable way of life[2].
Conclusion
The COVID-19 pandemic is a global health concern, with scientists working around the clock to develop treatments and preventative vaccines to counteract this threat. However, the “Misinformation pandemic” has led to public confusion about the safety and effectiveness of approved vaccines. Therefore, scientists led expert panel discussions to address concerns and answer questions (some of which I have shared with you here). Vaccination programmes are imperative to control the spread of fast spreading infectious diseases with high mortality, such as COVID-19. Vaccines provide stronger and longer-lasting immunity than naturally acquired immunity. Fast vaccine development and approval was enabled by massive government investment and parallel-running trials. The long-term adverse health effects from COVID-19 outweigh any potential vaccine long-term risks. Vaccination programmes are a community initiative, aimed at protecting everyone, including those who cannot be vaccinated. The future of humanity requires a more sustainable lifestyle to protect our planet from new and re-emerging infectious diseases.
References
1. The Royal Society, 2021. The Royal Society.
2. Prof. Brian Cox, Prof. Melinda Mills, Prof. Charles Bangham and Dr Rino Rappuoli: The Royal Society, 2021. The Race for a Vaccine.
3. ZOE Symptom Study, 2021. ZOE Symptom Study.
4. Dr Anna Goodman and Prof. Tim Spector: ZOE Symptom Study, 2021. Covid-19 Vaccines: What we know so far.
5. University of Southampton, 2021.University of Southampton.
6. Prof. John Holloway, Prof. Rob Read, Prof. Saul Faust and Prof. Lucy Yardley OBE: University of Southampton, 2021. Beating COVID-19 - Vaccines, Trials and Prevention.
7. The Open University, 2014. SK320 Infectious Disease and Public Health: Block 1.
8. GOV.UK, 2021. Information for UK recipients on Pfizer/BioNTech COVID-19 vaccine.
9. GOV.UK, 2021. Regulatory approval of COVID-19 Vaccine AstraZeneca.
10. World Health Organization, 2021. COVID-19 Vaccines.
11. Amit, S., Regev-Yochay, G., Afek, A., Kreiss, Y. and Leshem, E.: The Lancet, 2021. Early rate reductions of SARS-CoV-2 infection and COVID-19 in BNT162b2 vaccine recipients.
12. World Health Organization, 2021. WHO lists two additional COVID-19 vaccines for emergency use and COVAX roll-out.
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