Coronavirus-19 (COVID-19) vaccination has been widely hailed as our ticket out of a global pandemic that has wreaked havoc on healthcare systems and socio-economic equilibria all over the world. The World Health Organization (WHO) calculates that economic losses of USD 375 billion every month can be prevented with the introduction of global vaccination. The average duration for developing a new vaccine is approximately 10 years.1 Nevertheless, a little more than one year after COVID-19 was first recognized, no less than nine vaccines have been approved in different jurisdictions. However, we are not out of the woods yet; logistical challenges, vaccine skepticism, and new variants cast an ominous shadow over the finish line of the COVID-19 vaccine race.
The four types of vaccine
Vaccines train an individual’s immune system against a particular illness without giving them the disease itself. They do this by purposefully introducing the virus into the host’s body; either in the form of a weakened version of the entire virus, or a portion of the virus, or simply its genetic material. These non-virulent forms of the pathogen trigger specific immune responses that create immune memory, enabling the body to fight off COVID-19 if exposed to it in the future.
1. Inactivated virus: The most traditional of these approaches involves introducing an inactivated or significantly weakened virus to the body. The virus is too weak to cause a full-blown infection but strong enough to trigger an immune response. Currently, the CoronaVac vaccine (developed by Sinovac) and BBiBP-CorV (developed by Sinopharm) both use an inactivated virus.
2. Protein fragments: Another method involves simply introducing protein fragments of the COVID-19 virus into the host. Similar to the inactivated virus, these fragments can induce an immune response but do not cause the actual illness. Novavax, an American vaccine development company, is using this technology and has just entered Phase III clinical trials.
3. DNA fragments in a viral vector: A more complex approach involves delivering DNA fragments of COVID-19 using an unrelated virus, also known as a viral vector. Once the viral vector is in the human body, cells will use the genetic material to make a specific COVID-19 protein, which will trigger an immune response. Examples of COVID-19 vaccines using viral vectors include the University of Oxford/AstraZeneca vaccine and the Sputnik V vaccine developed by Gamaleya.
4. mRNA fragments in lipid nanoparticles: The newest and perhaps most-discussed strategy for developing vaccines involves using mRNA, which is an intermediate between DNA and proteins. The concept supporting this new technology is simple; researchers create specific mRNAs in the lab that can cause the body’s cells to generate harmless proteins that resemble the distinctive proteins of COVID-19. These proteins will then trigger an immune response, thereby training the immune system for exposure to the real virus.
The main advantage of this method is that since the cells in the host are producing the COVID-19 viral proteins, it is almost certain that they will make enough to generate the desired magnitude immune response. Furthermore, they actually generate a stronger type of immunity as they stimulate the immune system not only to make antibodies but also immune system killer cells. However, getting these mRNA strands from the laboratory into human cells is difficult. To protect them on their journey, they are wrapped in easily absorbable but exceptionally fragile fatty bubbles known as lipid nanoparticles. These require storage at very low temperatures of approximately –70°C, creating a significant supply chain distribution challenge. Despite these issues, Pfizer/BioNTech and Moderna vaccines, both of which apply this strategy, have been rolled out successfully in vaccination centers worldwide.
Accelerating toward herd immunity
With the development and approval of multiple COVID-19 vaccines, the focus has shifted to the logistical and social challenges of vaccinating enough people to create herd immunity. Herd immunity occurs when a significant proportion of a population is immune to an infectious disease, making the spread of the disease unlikely. In turn, this provides indirect protection (or herd immunity) to those who are not immune to the disease. This is particularly important to those who cannot be vaccinated, such as infants or individuals who have compromised immune systems. The herd immunity threshold for COVID-19 is not yet known but estimates indicate that it should be approximately 60%–75%. In a highly globalized world, achieving herd immunity in an isolated region or country is an insufficient approach for stopping the virus; instead the entire world’s population has to be inoculated.
Inequalities in access to vaccines
The Financial Times estimated that as of February 24, 2021, more than 212 million vaccine doses have been administered in 105 locations. However, distribution is by no means even; approximately 30% of doses were administered in the United States, 20% in China, 13% in the European Union, and 9% in the UK. India has only administered one-fifth as many doses as the US, despite having four times the population, and many developing countries have administered no vaccines at all.
To overcome huge inequalities in the context of the current COVID-19 pandemic, the World Health Organization along with other organizations, have created the Access to COVID-19 Tools (ACT) Accelerator, which includes a vaccines pillar called COVAX that aims to offer doses to at least 20% of all countries’ populations. Most developed countries have contributed to this initiative; among them, G7 leaders have collectively committed more than USD 4.3 billion. These investments will bring ACT’s total funding to USD 10.3 billion; however, this is still only a quarter of the USD 38.1 billion needed.
Bottlenecks in global vaccine distribution
Funding is not the only issue involved in addressing vaccine inequalities. The mRNA-based vaccines, which require ultra-cold storage (–70°C for the Pfizer/BioNTech vaccine and –20°C for the Moderna vaccine) create logistical issues for their distribution in developing countries. However, researchers have pointed out  that Ebola vaccines, which also require ultra-cold chain storage, have been successfully used in a small number of African countries.[9,10] Furthermore, countries can also opt to receive the University of Oxford/AstraZeneca vaccine, which only requires normal refrigerated temperatures of 2°C–8°C.
The transportation of vaccines will only be problematic if, in fact, there are enough vaccines for global distribution. The three main vaccines have reported an estimated total production capacity of 5.3 billion doses for 2021. This may be enough for 2.6 billion people, i.e., one-third of the global population, if distributed evenly. However, wealthy nations are “hoarding” vaccines by pre-ordering them from pharmaceutical companies while they are still in Phase III trials. For example, at the end of 2020, Canada purchased 9.6 doses of vaccine per person while the UK secured 5.5 doses per person. In contrast, Latin American countries averaged only 0.4 doses per person, and the African Union had purchased only 0.2 doses per capita. Although developed nations are now pledging to donate surplus vaccine supplies to poorer countries, the Economist Intelligence Unit estimates that vaccine coverage in developing countries will not (if ever) become widespread until 2023.
Overcoming vaccine skepticism and misinformation
The development of nine COVID-19 vaccines in less than one year is an incredible feat of global scientific, industrial, and governmental cooperation, celebrated by many. However, a significant proportion of the public has been met with skepticism, distrust, and confusion, leading many people to opt-out of receiving the vaccine.
Vaccine hesitancy is often linked to mistrust and a lack of confidence in the government and the pharmaceutical industry fueled by myths and misinformation. However, for COVID-19 vaccines, the situation is even more complex. The use of novel technology, along with the rapid development and approval process of vaccines, has cast doubt on the COVID-19 vaccines, even among healthcare workers. In fact, up to 40% of frontline health workers in Los Angeles County and 60% of care home workers in Ohio turned down the vaccine when they were first offered the opportunity to receive it.
Despite fears and reluctance among some, the data to date supports only one conclusion: COVID-19 vaccines are safe and effective. In Phase III clinical studies, all three vaccines approved in the United Kingdom reported excellent vaccine efficacy rates (94.1% for Moderna, 95% for Pfizer/BioNTech, and 82% for University of Oxford/AstraZeneca) with minimal side effects.
After fully vaccinating more than 27% of Israeli citizens, the local health ministry found the Pfizer/BioNTech vaccine to be 89% effective at preventing infection of any kind and 94% effective against symptomatic COVID-19 infection. This result was mirrored in research conducted in the U.K. across the universities of Edinburgh and Strathclyde, as well as Public Health Scotland, between December 2020 and February 2021. They found that the chance of hospitalization from four to six weeks after vaccination was 85% lower after receiving one dose of the Pfizer/BioNTech vaccine and 94% lower after one dose of the University of Oxford/AstraZeneca vaccine.
In short, the best available, published scientific literature unambiguously supports the safety and efficacy of the approved COVID-19 vaccines. Suspicion and mistrust of these vaccines are primarily rooted in pre-existing suspicion and misunderstandings propagated by the reporting of complex scientific data through unqualified channels. As the vaccine roll-outs gain pace, this issue could become increasingly problematic if small clusters of non-vaccinated individuals act as incubators for the virus to mutate and side-step existing vaccines.
Navigating new variants
Despite the relative certainty regarding vaccine efficacy up to now, the future remains uncertain. Many scientists are concerned about whether vaccines can retain their efficacy against an evolving virus. There are already many thousands of variants of the COVID-19 virus circulating and it is not unreasonable to expect that variants will continue developing due to the high propensity of viruses to mutate. For the most part, these differences will be inconsequential; however, some can make the virus more infectious or even fatal.
Scientists are particularly concerned about variations that change the spike protein, which the virus employs to enter human cells. This “shapeshifting” protein can make it more difficult for the immune system to recognize and destroy the virus, particularly if it has been trained by vaccines based on previous forms. At present, selected research is already showing that the variants with the E484K mutation may help the virus evade antibodies, while several vaccines (including the University of Oxford/AstraZeneca, Pfizer/BioNTech, and Moderna versions) have all reported potentially reduced efficacy against the 501Y.V2 viral variant, first identified in South Africa. To combat this worrying trend, researchers have already begun preparing for clinical studies on vaccines targeted at new virus variants and plan on rolling out booster vaccines.
The production of COVID-19 vaccines in record-breaking time has been nothing short of extraordinary. Nevertheless, the discovery of these vaccines is only the first step on a long path to global stability. While it is unlikely that there will be ‘winners’ in the race to end the pandemic, the vaccines represent a promising solution to get us across the line. The question that remains is whether we can achieve the seamless, unified cooperation needed on a global scale to eradicate existing forms of COVID-19 before vaccine-resistant variants have a chance to take hold.
1. Pronker ES, Weenen TC, Commandeur H, Claassen EHJHM, Osterhaus ADME. Risk in Vaccine Research and Development Quantified. PLoS One. 2013;8(3):57755. doi:10.1371/journal.pone.0057755
2. Zhang Y, Zeng G, Pan H, et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18–59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis. 2021;21(2):181-192. doi:10.1016/S1473-3099(20)30843-4
3. Xia S, Wang Y, Zhang W, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial. Artic Lancet Infect Dis. 2020;21:39-51. doi:10.1016/S1473-3099(20)30831-8
4. Mahase E. Covid-19: Novavax vaccine efficacy is 86% against UK variant and 60% against South African variant. BMJ. 2021;372. doi:10.1136/bmj.n296
5. Understanding mRNA COVID-19 Vaccines | CDC. Accessed March 10, 2021. https://www.cdc.gov/coronaviru...
6. Fox SJ, Potu P, Lachmann M, Srinivasan R, Meyers LA. The COVID-19 herd immunity threshold is not low: A re-analysis of European data from spring of 2020. medRxiv. Published online December 3, 2020:2020.12.01.20242289. doi:10.1101/2020.12.01.20242289
7. Covid-19 vaccine tracker. Accessed March 10, 2021. https://ig.ft.com/coronavirus-...
8. G7 leaders commit US$ 4.3 billion to finance global equitable access to tests, treatments and vaccines in 2021. Accessed March 10, 2021. https://www.who.int/news/item/...
9. Ebola vaccine delivery shows how Covid vaccine can work in Africa — Quartz Africa. Accessed March 27, 2021. https://qz.com/africa/1936803/...
10. Jusu MO, Glauser G, Seward JF, et al. Rapid Establishment of a Cold Chain Capacity of –60°C or Colder for the STRIVE Ebola Vaccine Trial During the Ebola Outbreak in Sierra Leone. J Infect Dis. 2018;217(suppl_1):S48-S55. doi:10.1093/infdis/jix336
11. Mullard A. How COVID vaccines are being divvied up around the world. Nature. Published online November 30, 2020. doi:10.1038/d41586-020-03370-6
12. More than 85 poor countries will not have widespread access to coronavirus vaccines before 2023 - Economist Intelligence Unit. Accessed March 10, 2021. https://www.eiu.com/n/85-poor-...
13. Holpuch A. “I’m not an anti-vaxxer, but...” US health workers’ vaccine hesitancy raises alarm | World news | The Guardian. The Guardian. Published 2021. Accessed February 23, 2021. https://www.theguardian.com/wo...
14. Baden LR, El Sahly HM, Essink B, et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2021;384(5):403-416. doi:10.1056/NEJMoa2035389
15. Polack FP, Thomas SJ, Kitchin N, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020;383(27):2603-2615. doi:10.1056/NEJMoa2034577
16. Voysey M, Clemens SAC, Madhi SA, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021;397(10269):99-111. doi:10.1016/S0140-6736(20)32661-1
17. Israel finds BioNTech/Pfizer vaccine reduces virus transmission | Financial Times. Accessed February 23, 2021. https://www.ft.com/content/262...
18. Vasileiou E, Simpson CR, Robertson C, et al. Effectiveness of First Dose of COVID-19 Vaccines Against Hospital Admissions in Scotland: National Prospective Cohort Study of 5.4 Million People. SSRN Electron J. Published online 2021. doi:10.2139/ssrn.3789264
19. New coronavirus variants | New Scientist. Accessed March 27, 2021. https://institutions.newscient...
20. Wise J. Covid-19: The E484K mutation and the risks it poses. BMJ. 2021;372:n359. doi:10.1136/bmj.n359
21. Oxford/AstraZeneca jab fails to prevent mild and moderate Covid from S African strain, study shows | Financial Times. Accessed March 10, 2021. https://www.ft.com/content/e9b..
Belinda Ding is a scientific consultant at Biochromex. She is a PhD-level Clinical Neuroscientist at the University of Cambridge. Her research focuses on developing cutting-edge MRI techniques for ultra-high field imaging.