With roughly 71 million COVID-19 vaccine doses administered worldwide, 24.5 million doses given in the United States alone, humanity is experiencing one of the largest-scale global health efforts in history. There are dozens of different COVID-19 vaccines in various stages of development throughout the world that have the potential to be approved. As of writing this article, the World Health Organization (WHO) has identified 63 vaccine candidates in the clinical phase. Currently, the vaccines authorized for emergency use in the United States are the Pfizer-BioNTech and Moderna mRNA vaccines. These vaccines are a great first step into widespread vaccination, but there are several barriers limiting their use.
One of the biggest challenges for mRNA vaccines is their extremely strict storage requirements for stability, which are not unique to the Pfizer or Moderna formulations. The Pfizer vaccine is supplied as a frozen, 5-dose vial that is stored between -80ºC to -60ºC and has to be thawed and diluted prior to administration. After dilution, they have to be stored between 2ºC to 25ºC and used or discarded within 6 hours from the time of dilution. The Moderna vaccine also comes in multi-dose vials but has slightly less strict temperature requirements. They are stored frozen between -25ºC to -15ºC, but can be stored refrigerated between 2ºC to 8ºC up to 30 days prior to first use. Another limitation is that the Pfizer vaccine is recommended for people aged 16 years and older, while the Moderna vaccine is approved for people aged 18 years and older. If these mRNA vaccines have so many drawbacks, what other options will there be in the future?
Despite the fact that the only COVID-19 vaccines currently available are mRNA vaccines, this vaccine type is actually relatively new and uncommon. To date, there are no other approved mRNA vaccines on the market. According to the WHO’s novel coronavirus vaccine landscape, only 7 of the 63 vaccines in development are RNA based. An additional 9 vaccines under development are DNA-based. In contrast, there are 20 protein subunit vaccines in clinical development. Another 16 vaccines in the viral vector class as either replicating or non-replicating varieties with or without additional antigen presenting cells are also identified. In the whole virus vaccine category, there are 9 inactivated virus vaccines and 1 live attenuated vaccine.
The latest vaccine that has been approved in the UK is a viral vector vaccine developed by AstraZeneca and the University of Oxford. The vaccine has a reported efficacy of 90% and is stable for refrigeration. Their clinical trials, which involved over 11,000 people, found the vaccine’s 90% efficacy figure in those that received a low dose followed by a standard dose. Surprisingly, in participants that received two standard doses the efficacy of the vaccine was only 62.1%. One of the major benefits of the vaccine is its price of $4 per dose, much lower than the $20 of the other available vaccines. However, there have been problems with supply and pricing. The UK has ordered 100 million doses, Australia has ordered 53 million, and the EU has a contract with AstraZeneca to provide up to 400 million doses in total, around 80 million of which were due this quarter. Unfortunately, AstraZeneca reported on January 22 that they will only be able to deliver 31 million doses to the EU and supply chain issues likely affect their other agreements as well. The U.S. still has not approved the vaccine due to delays in clinical trials.
Some other major viral vector vaccines production includes Jannsen/Johnson&Johnson’s vaccine, which also has an agreement for 400 million doses with the EU once its year-long clinical trial is finished. They launched their phase 3 trials in Latin America and the UK in fall of 2020. The Ganekaya Research institute in Russia is also developing a viral vector, called Sputnik V, that has just entered phase 3 trials. It has a reported effectiveness of 92% and can be stored at normal fridge temperatures. Another U.S. based biotech company, Novavax, has recently finalized an agreement with Canada to purchase 52 million doses and concluded talks with the EU for up to 200 million doses for their fridge-stable protein subunit vaccine. The French company Sanofi and England-based GSK also have a protein subunit vaccine that is stable at refrigerator temperatures and can even be stored at room temperature for a short amount of time. The EU has already confirmed the purchase of 300 million doses of their vaccine. Additionally, Sanofi has just finished settling an agreement to assist in producing 100 million doses of the Pfizer/BioNTech vaccine just hours before writing this article.
Information on vaccines in development in China is more difficult to obtain, but Sinovac’s inactivated vaccine is currently approved for emergency use in China. The country currently has the second highest number of vaccines given in the world at 15 million in total. Other countries have already reached agreements with Sinovac, such as Turkey approving 10 million doses of the vaccine. The latest figures of its effectiveness put it at around 50.4%, making it an unlikely contender at its reportedly $60/dose price tag. Sinopharm, which is a state-run company, is also developing two inactivated vaccines of its own. Reports of its efficacy are a little inconsistent but hover around 80% effectiveness. Regardless, the United Arab Emirates has already approved the Sinopharm vaccine earlier this month.
The vaccines mentioned in this article are nowhere near an exhaustive list of all the potential vaccines that may come out to protect against COVID-19, which is great news. As the effort to push for global immunity to the virus that turned the world on its head continues, it’s reassuring to know that several different options will eventually become available for the public in the coming years. More than likely, a set of gold-standard vaccines will be developed in the years to come that will join the likes of influenza on the list of regularly scheduled vaccinations.
Written by: Kervin Novido
With the Rapid Development of Several COVID-19 Vaccines, is Coronavirus Finally on its Way Out?
As of 11 March 2020, the world has been in the midst of a pandemic. A once meaningless word to many, ‘coronavirus’ has taken the world by storm. In fact, Google revealed last December that ‘coronavirus’ was the top trending search for the UK in 2020. Coronaviruses are a family of viruses that cause infection in humans and animals. The one that led to the pandemic is called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but is more commonly referred to as simply ‘coronavirus’. When an individual is infected with the virus, they may display mild symptoms or no symptoms at all. Consequently, if the individual displays more severe symptoms and potentially need to be hospitalised, they are said to have coronavirus disease or COVID-19. An insidious infectious disease, the impact of COVID-19 has been catastrophic. Since the beginning of the pandemic, one clear solution to eliminate this disease and aid in the return to normal life has been the development of an effective vaccine. With COVID-19 vaccines having been approved for use in the UK and worldwide, is the pandemic finally over?
Vaccines are chemically weakened or dead forms of a pathogen, whereby a pathogen is a microorganism which results in disease. Once a person is treated with a vaccine i.e. they are vaccinated, their immune system is stimulated. This stimulation leads to destruction of the pathogen and the production of memory cells. This means that if a person was infected with the same pathogen in the future, the body remembers how to fight the pathogen. There are several types of vaccines which exist. The four main types of vaccines are live vaccines, inactivated vaccines, subunit vaccines and nucleic acid-based vaccines.
The first type, live vaccines, include commonly administered injections such as MMR and tuberculosis vaccines. As the name suggests, they contain the actual microorganism which causes the disease. However, they don’t make people ill due to attenuation, which is a process whereby the microorganisms are reduced in virulence (capability to cause severe disease). This is possible as vaccine developers only use the mutated strains of the organism that have a lower toxicity. However, as they still contain the actual disease-causing microorganism, they cause the body to produce many antibodies. This results in lifelong immunity against the disease.
The second type, inactivated vaccines, are made from dead microorganisms. They are safer compared to the live ones, but a higher dose is often needed as the bacteria and viruses don’t replicate inside the body. This makes them more expensive compared to live vaccines. An example of an inactivated vaccine is the polio vaccine. The third vaccine type are subunit vaccines, such as the hepatitis B vaccine. As the name suggests, they only include the antigen parts of the microorganism, which is the part that stimulates our body’s immune system.
The final vaccine type is the nucleic acid vaccine, which contains plasmid DNA or mRNA from the bacteria/virus that codes for the antigens that cause an immune response. These mRNA vaccines are considered safe and very effective, which is why they are increasingly being developed. The current vaccines against COVID-19 encompass the second, third and fourth vaccine types; for example, Sinopharm has produced an inactivated virus vaccine, AstraZeneca/Oxford has produced a subunit vaccine and Pfizer has produced an mRNA vaccine. Currently in the UK, the Pfizer, Moderna (another mRNA vaccine) and AstraZeneca/Oxford vaccines have all been approved for use.
A report published by Imperial College London’s Institute of Global Health Innovation (IGHI) and YouGov in November 2020 looks at people’s attitudes towards COVID-19 vaccines across 15 countries, including the UK. This report was based on survey responses from around 13,500 people and gives an insight into behaviours related to COVID-19. 65% of respondents in the UK reported being willing to get vaccinated in 2021 if a COVID-19 vaccine became available to them, which made respondents from the UK the most willing to be vaccinated among the countries surveyed. Overall, of all those surveyed, around half (51%) were willing to get a COVID-19 vaccine in 2021.
This also reveals how half of those asked, the other 49%, would be hesitant in getting a COVID-19 vaccine if it was available to them. This is not a new concept when it comes to vaccines; vaccine hesitancy has existed for many years and is in fact a global issue. The World Health Organization (WHO) recently listed vaccine hesitancy as one of their top 10 biggest threats to global health. Vaccine hesitancy is the scientific term for anti-vaccination; it is when people with access to vaccines delay or refuse vaccination. Vaccination is one of the most effective ways of eliminating disease across the world, with a staggering 2 to 3 million deaths prevented by vaccination every year. Nonetheless, vaccine hesitancy has grown in popularity in recent years, fuelled by misconceptions and misinformation. This could have potentially devastating consequences on public health.
The biggest concern people have regarding the COVID-19 vaccines is whether they are safe. Many are hesitant to be vaccinated as they feel the vaccine was developed too quickly, with the time taken from initial development to the deployment of the vaccines being approximately a year or less. Thus, people are concerned that long-term studies of the vaccines have not been conducted, and so are afraid of the potential long-term implications of a COVID-19 vaccine. An article published by the COVID Symptom Study addresses this concern. The COVID Symptom Study is the world’s largest ongoing study of COVID-19. The study is based on data provided by over 4 million people globally through the COVID Symptom Study app. It is a non-profit initiative launched by health science company ZOE in collaboration with King’s College London.
The article explains that the global health emergency created by the pandemic led to billions of pounds being committed to global COVID-19 vaccine research, as well as tens of thousands of people volunteering for the clinical trials of the vaccine. The level of funding for the vaccine meant that scientists all over the world were working on a vaccine and had the means to do so, making the process of vaccine development much faster. In addition, the large number of volunteers for clinical trials further increased the rate of vaccine development, as it can take many months or years to obtain enough volunteers. Furthermore, the genetic code of SARS-CoV-2 was identified quite quickly relative to the spread of disease (January 2020), so scientists were able to begin working on a vaccine immediately. The vaccines were not developed from scratch, rather they were developed based on existing safe and effective vaccine delivery systems. These were adapted to work against COVID-19. For example, the AstraZeneca/Oxford vaccine had been in development and testing for 15 years, having been previously developed to work against other related coronaviruses that cause SARS and MERS. In addition, compared to the past vaccines can be manufactured at a much quicker rate due to modern technology.
It is a culmination of these factors which led to the fast development of COVID-19 vaccines. If faced with vaccine hesitant members of the public, it is important to inform them that the safety precautions, clinical trials and tests for the COVID-19 vaccines were conducted as thoroughly as with any other vaccine. The spread of misinformation is especially worrying now as vulnerable patients who see or hear it may refuse the COVID-19 vaccine, thus endangering their life and the health of those around them. Ensuring we are fully educated about the history and development of this virus and its treatment can be what saves them in the future.
Authors: Amelia Ryan and Nusayba Ali