The development of a COVID-19 vaccine is critical to slow down the spread of the virus. However, the rapid race to develop this vaccine has raised concerns.
An emergence
In December 2019, an unexplained group of pneumonia cases emerged across Wuhan, China, which drew the attention of health authorities. Epidemiological investigations traced the infection in humans back to a seafood market in Wuhan. On January 3rd 2020, the World Health Organisation (WHO) were notified about the epidemic by the Chinese government. By January 7th 2020, the causative pathogen was identified as a novel coronavirus provisionally called 2019-nCoV. On February 11 2020, WHO announced the official name for the disease – COVID-19 – an acronym of coronavirus disease 2019. Since then, there has been a rapid response from public health, clinical and scientific communities worldwide to determine the epidemiology of the infection.
A novel SARS virus
In the past two decades, two other coronavirus epidemics have occurred. The first being SARS-CoV in China which resulted in approximately 8,000 cases and 800 deaths. The second was MERS-CoV that began in Saudi Arabia and caused approximately 2,500 cases and 800 deaths. MERS-CoV cases still sporadically appear today. The new virus, termed SARS-CoV-2 by the International Committee on Taxonomy of Viruses, was named due to its phylogenetic proximity to the previous SARS-CoV virus. Both of these viruses originated in bats, which are likely to act as a reservoir host.
Several studies, using advanced technologies, have determined the characteristics of this virus. SARS-CoV-2 is a β-coronavirus, belonging to the subfamily Coronavirinae. It is an enveloped, positive-sense, single-stranded RNA virus. The genome size of SARS-CoV-2 varies from 29.8 kb to 29.9 kb and encodes several important structural proteins including spike (S) glycoprotein, small envelope (E) glycoprotein, membrane (M) glycoprotein and nucleocapsid (N) protein. It also contains several accessory proteins.
The entry of SARS-CoV-2 is mediated by the recognition of the receptor binding domain in the S protein and the angiotensin converting enzyme 2 (ACE2) receptor on the surface of the host cell. The activation of S protein is primed by the serine protease TMPRSS2. Researchers have found that the affinity of S protein of SARS-CoV-2 to ACE2 was greater than that of SARS-CoV. Blocking viral entry has been studied extensively to try and help identify a potential therapeutic target or vaccine.
A public health nightmare
Since its initial emergence in Wuhan, the virus has rapidly spread through China and across the globe. At the time of writing, there are approximately 22,235,623 coronavirus cases and 784,765 deaths worldwide. The main symptoms of coronavirus include a high temperature, a persistent cough and loss or change to sense of smell or taste. The emergence of the virus resulted in widespread interest due to the range in severity of symptoms. Whilst some cases can result in hospitalisation and/or death, 20 to 40% of people with the disease are completely asymptomatic. Researchers have already identified several factors which influence severity, including age, ethnicity/race and health co-morbidities. Nonetheless, the true complexity of the virus is likely to be multi-faceted.
The virus has had an unprecedented impact on healthcare, the economy and people’s lives. Strict lockdown regimes have and continue to have a detrimental impact on general healthcare and societal norms. Conflicting evidence and advice given by governments across the world has resulted in mass confusion.
Vaccination across the nation
With no apparent end to the pandemic, attention has quickly shifted to the development of a vaccine. However, vaccine development is historically an expensive and lengthy process which can take years to reach approval.
There are typically fives stages to developing a vaccine:
- Discovery research – takes 2-5 years and involves lab-based research exploring ways to induce an immune response at a molecular level
- Pre-clinical stage – takes 2 years and involves animal testing to evaluate the safety and suitability of potential vaccines for humans
- Clinical development – involves testing vaccines in humans
- Phase I – testing for safety – takes 2 years and requires 10-50 individuals to participate in trials
- Phase II – understanding the immune response – takes 2-3 years and requires hundreds of individuals to participate in trials
- Phase III – evaluating if the vaccine candidate protects against the disease – takes 5-10 years and requires thousands of individuals to participate in trials
- Regulatory review and approval – involves submitting data and information to regulators to gain approval for vaccines and can take 2 years
- Manufacturing and delivery – requires specialist facilities that are highly regulated and expensive to develop
Following these steps would mean that a traditional vaccine could take more than 10 years to be developed – this is not fast enough for a COVID-19 vaccine.
Elected candidates
Developing a vaccine at such speed, whilst ensuring safety, has caused a lot of scepticism. Russian President Vladimir Putin’s announcement that Russia has approved the world’s first COVID-19 vaccine has caused widespread concern. Scientists globally have claimed that the process has been rushed and is inappropriate. Russia has not completed large trials to test the safety and efficacy of the vaccine. It has only been tested in 76 people. This step could endanger the lives of civilians and impede global efforts to develop a quality vaccine. This move by Putin has caused concern that President Donald Trump too will push for early authorisation of a vaccine in the United States to help his re-election campaign.
The race to find a vaccine, which has been compared to the space race, has seen a vast amount of potential vaccine candidates taken to clinical trials. WHO recently released a draft landscape of these potential candidates. A summary of the most promising candidates can be found below:
Oxford University and AstraZeneca
- Name: ChAdOx1 nCoV-19
- This vaccine is a viral vector vaccine and is made from a genetically engineered virus that causes the common cold in chimpanzees. The virus is non-replicating and has been modified to express the SARS-CoV-2 S protein. The recent phase 1/2 trials of this vaccine have shown promise. The vaccine was found to induce a strong immune response and currently appears to be safe.
Sinovac
- Name: CoronaVac
- The biopharmaceutical company have developed an inactivated vaccine that uses a non-infectious version of the virus to induce an immune response. The vaccine was found to induce neutralising antibodies in over 90% of people.
Moderna
- Name: Mrna-1273
- This approach delivers genetic material to human cells that instruct them to make S proteins. To date no mRNA vaccine has ever been approved for an infectious disease. The vaccine was found to induce an immune response during the first stage of the study yet required a second injection to induce a dramatic immune response.
Pfizer and BioNTech
- Name: BNT162b2
- This vaccine, using the same technology adopted by Moderna, is a mRNA based vaccine. Recent phase1/2 trial results for this vaccine revealed higher levels of COVID-19 antibody titre than typically seen in infected people after 28 days from administration.
The development of a vaccine is a monumental task. The ability to get these vaccines into clinical trials would not have been possible without significant investment and international collaboration. Nonetheless, it is critical that efforts to approve a vaccine are not overshadowed by competition and greed. No corners should be cut. No results should be fabricated. Transparency is of the utmost importance. Even if a safe and effective vaccine is developed, it is the public’s trust that will determine the true effectiveness of the vaccine.
The wealthy get healthy
Although promises have been made that vaccines will be affordable and accessible to all, it is unlikely that the doses will meet the demand of 7.8 billion people in the world. From the stockpiling of toilet roll to the disproportionate distribution of personal protective equipment (PPE), disadvantaged communities across the world have been the hardest hit by the pandemic. Therefore, concerns among poorer nations and health advocates about how wealthier countries may monopolise on vaccine supply are well founded.
The investment in production capacity across the world has been seen to be a key player in solving this dilemma. Several collaborations have been formed, including the University of Oxford and AstraZeneca partnership, to ensure mass production of vaccinations.
An initiative known as COVAX – set up by WHO, the Coalition for Epidemic Preparedness Innovations and Gavi, the Vaccine Alliance – has so far seen 165 countries across the world join in support of equitable and broad access of a vaccination. The collaboration aims to accelerate the development and manufacturing of COVID-19 vaccines and to ensure that there is fair and equitable access for every country.
The future
A recent feature published in Nature discussed the potential future of the pandemic. It highlighted that epidemiologists’ projections all agree on two things – that COVID-19 is here to stay and that the future is dependent on a lot of unknowns. These unknowns include whether the virus provides lasting immunity, whether seasonality impacts the virus and what choices the government and individuals make.
It is clear that the pandemic is playing out differently in different places. For example, a strict lockdown regime in New Zealand has resulted in a low level of cases. Whereas, cases in other countries such as the United States are rising fast due to an easing of lockdown restrictions.
Nevertheless, the world as we once knew it has changed. Personal and social behaviours, such as handwashing and mask wearing, are likely to persist for a long time. The impact that this pandemic has had on mental health cannot be underestimated. In addition, we are yet to discover the true extent of how many lives have been lost and will continue to be lost as a result of the suspension of healthcare services. The need for collaboration and community has never been more important.
We must all come together to make a difference. We must be a part of the change; not apart from it.
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