A look at factors enabling the unprecedented rapid development and subsequent rollout of COVID-19 vaccines, and lessons on improving access to vaccines in the future.
Vaccines have slashed child mortality rates, extended life expectancy, protected billions from disability and death, and eradicated diseases. In the developed world, it has been about two or three generations since diseases like smallpox, polio and diphtheria threatened to eradicate human life. Until COVID-19, infectious diseases in high-income countries (HICs) were little more than distant memories.
Ironically the success of vaccines in reducing the transmission of, if not eliminating infectious diseases, has led people to forget their critical role in public health. Many diseases which have been eradicated in HICs in the last century continue to claim lives and impoverish communities. About 94% of all global deaths from infectious diseases occur in low- and middle-income countries (LMICs), and more than half of them from vaccine-preventable diseases [1,2].
Unprecedented Rapid Development of COVID-19 Vaccines
Many factors contributed to the unprecedented rapid development of the first COVID-19 vaccines after the World Health Organization (WHO) declared COVID-19 a pandemic. They included breakthrough technologies particularly in the field of mRNA, unusually high degrees of cooperation and information-sharing among government bodies, big pharma, non-profit organisations (NPOs), and academia; in particular, partnerships between academia and pharma in pre-pandemic research, as well as, in some cases, subsequent pre-clinical research and clinical trials of the resulting vaccines.
For decades, the biggest hurdles in vaccine development have been the cost of early discovery and development stages, as well as the time and funding required for clinical trials. The sequential approach to vaccine development could cost billions of US dollars and take between 10 to 15 years to complete.
One of the key enablers that accelerated the access to COVID-19 vaccines was the initial emergency use authorization (EUA) issued by the United States Food & Drug and other authorities. The huge potential benefits of vaccines were seen to outweigh the apparently low risks, significantly shifting the regulatory risk tolerance curve to the left. The United States' Operation Warp Speed during the Trump administration and similar undertakings in Europe and China condensed the sequential vaccine development approach and forced the discovery and development stages to run in parallel.
Massive amounts of government funding and the race to pre-order millions of doses even before trials were completed removed much of the financial risk, enabling big pharma to devote huge amounts of resources to the hunt for a vaccine. Because it was a pandemic, there was an abundance of cases to rapidly assess vaccine efficacy. The promise of speedy approvals and guaranteed markets also removed much of the risk for the industry, so manufacturing capacity could be safely scaled up while clinical trials were still ongoing [3,4,5].
Another enabler was technology transfers. According to the Developing Countries Vaccine Manufacturing Network (DCVMN), technology transfers enabled their members to produce almost 6 billion of the 11 billion doses of COVID-19 vaccines manufactured globally in 2021.
“Collaborations and technology transfers have always played an important role in vaccine manufacturing, even pre- pandemic, but the pandemic certainly provided a great stimulus to expedite technology transfers to help make vital vaccines available for billions of people worldwide,” says Rajinder Suri, Chief Executive Officer, DCVMN.
DCVMN also increased the production of many of the other vaccines they produce, more than tripling the total global vaccine production from 3.5 billion in 2019 to 11.3 billion, including COVID-19 vaccines, in 2021 [6].
Addressing Inequitable Vaccine Distribution
The success of rapid development of COVID-19 vaccines was marred by the inequitable global distribution of those vaccines.
Wealthy nations like United Arab Emirates (UAE) claimed to have given 99% of its population two doses of the vaccine, while resource-poor Republic of Burundi had only managed to give 0.1% of its population the first dose. All but four of the 20 least vaccinated countries in the world are in Africa. By the end of April 2021, only one of the 54 countries in Africa had reached or exceeded the then global vaccination rate of 66.8%, and less than 48% of the population in 50 African countries had received a first vaccine shot [9].
In addition to the unavailability of vaccines in LMICs, other factors that complicated and delayed getting shots in arms for many in lower-income populations included overstretched healthcare systems, limited experience with mass adult vaccination, poor cold chain logistics infrastructure, lack of financing or political will to address these problems, civil unrest, and the lack of community buy-in for new vaccines. Key observations were made about the different levels of pandemic preparedness and uneven vaccine rollout in HICs and LMICs:
1. Varied levels of pandemic preparedness
The previous experience that some Asian countries had gained with disease outbreaks such as Nipah, Severe Acute Respiratory Syndrome (SARS) and MERS, had taught them valuable lessons on how to contain the early spread of disease outbreaks, and meant they were much more prepared to cope with a new threat. Others were slower to react and impose restrictions, while some underestimated the ability of the virus to spread rapidly. In some HICs and LMICs, politics influenced pandemic planning and responses that should have been left to public health professionals.
This unpreparedness and delay in response, although later corrected, contributed to the huge variance in the number of cases and deaths between different countries in the first few months of the pandemic [7].
2. Inequitable vaccine distribution
Once the threat of COVID-19 was established, vaccine development moved at an unprecedented speed. Unfortunately, while richer Western nations were able to secure a vast majority of the vaccines produced in 2021, LMICs were left struggling to secure enough doses to vaccinate the most vulnerable segments of their populations [1]. A ground-breaking global collaboration to accelerate the development, production and equitable access to COVID-19 tests, treatments, and vaccines – the Access to COVID-19 Tools (ACT) Accelerator – was established in April 2020.
The Organisation for Economic Cooperation and Development (OECD) issued a report in March 2021, calling for governments to act collectively to accelerate vaccination globally [8]. By early 2022, the distribution had improved significantly and COVAX, the vaccine pillar of the ACT Accelerator, announced hitting 1 billion distributed doses [2]. COVAX brought together governments, global health organisations, manufacturers, scientists, the private sector, civil society, and philanthropy in an effort to ensure fair and equitable access to vaccines for every country in the world.
3. Lack of facilities and infrastructure; weak supply chain
The disparity in vaccine distribution was exacerbated because LMICs often lacked the necessary infrastructure to store, distribute and use the vaccines. The shortcomings in supply chains and vaccination programme infrastructure in many LMICs were revealed as a result of the pandemic.
Standard cold-chain storage, logistics, and management services were often rudimentary, and the ultra-cold-chain logistics capabilities required by some mRNA-based COVID-19 vaccines were practically non-existent. Additionally, few LMICs had experience with large-scale, emergency, adult vaccination programmes.
4. Anti-vaccine misinformation
Vaccination programmes have always faced some suspicion and doubt, or what we today call ‘vaccine hesitancy’. While in the past it was sometimes regarded as a cultural issue, more often it was a lack of knowledge that could be addressed with localised educational outreach. However, in recent years, the problem has been exacerbated in both HICs and LMICs alike by misleading or plain false information spread largely via social media and the internet.
The Changing Regulatory Landscape
The Emergency Use Authorization (EUA) granted by USFDA for the first vaccine against SARS-CoV-2 was only possible because of the extraordinary collaborative efforts of regulatory agencies, allowing manufacturers to develop vaccines and scale-up manufacturing in parallel, along with the most intensive vaccine safety monitoring effort in US history to ensure safety [10].
However, many countries particularly LMICs, lacked the capabilities to expand and expedite regulatory capacity. Even the wealthiest countries struggled to sustain monitoring for extended periods. Moving forward, greater flexibility, innovation and capability need to be developed in regulatory agencies around the world – both to speed up the development and production of vaccines for known threats, and to prepare for future pandemics. The conservative nature of pre-COVID regulatory processes is no longer sufficient or useful.
Dr Raman Rao, Chief Executive Officer of Hilleman Laboratories, which published its White Paper on Vaccine Equity in November 2022, says, “Thought leaders from the global vaccine ecosystem are in broad agreement that the COVID-19 pandemic has brought us to an inflection point and presented us with an opportunity for change. COVID-19 has taught us valuable lessons and we should use the experience from this crisis to address unmet needs for vaccination. We need to act now and seize the opportunity to change the current global vaccine inequity into vaccine equity for all.”
In Conclusion
The COVID-19 pandemic forced the world to pay close attention to vaccines again and reinforced the importance of global cooperation and solidarity in facilitating broader access to vaccines from a spectrum of stakeholders – including international and supranational bodies, national governments, industry, donors, and NPOs – in combating infectious disease.
While the vaccination ecosystem has improved in recent decades, the reality is that more children around the world are being vaccinated today simply because the global population has grown by almost 50% in the last 30 years. That also means that the total number of children not receiving vaccines has also grown [3]. According to UNICEF, in 2020 around 23 million children were un- or under-vaccinated (not receiving the first dose of Diphtheria-Tetanus-Pertussis vaccine (DTP) or third dose of DTP respectively), and 17 million of them were “zero-dose children” who did not receive any kind of vaccines [11].
As Dr David C. Kaslow, Chief Scientific Officer, Program for Appropriate Technology in Health (PATH) says, “A formulation in a vial does not become a vaccine until it's injected into the arm of a recipient. It has become pretty apparent now with COVID-19 vaccines that it’s a whole lot easier to make billions of doses of vials filled with a formulation, and much, much harder to get those doses into the arms of people who might benefit from them.”
While there is a multitude of complex factors contributing to global vaccine inequity, it is imperative that we act today if we want to reduce the number of zero-dose children in the world before 2030.
The article has been adapted from the recently published White Paper on ‘Vaccines, Today and Tomorrow’ by Hilleman Laboratories, produced by Bridges M&C.
References:
[1] Mirza A & Rauhala E. Here’s just how unequal the global coronavirus vaccine rollout has been. May 2021. Accessed in Apr 2022.
[2] Guarascio F. Reuters. Global vaccine-sharing programme reaches milestone of 1 billion doses. Jan 2022. Accessed in Apr 2022.
[3] Vaccine Research & Development. Johns Hopkins University & Medicine. Accessed in May 2022.
[4] Hanney SR, Wooding S, Sussex J, Grant J. From COVID-19 research to vaccine application:why might it take 17 months not 17 years and what are the wider lessons? Health research policy and systems. 2020;18(1):1-0. Accessed in May 2022.
[6] Interview, Rajinder Suri, DCVMN. Suri R. Interviewed by the authors, Feb 24, 2022.
[7] WHO dashboard. WHO Coronavirus (COVID-19) Dashboard. Accessed in Apr 2022.
[8] OECD Policy Response to Coronavirus (covid-19). Access to COVID-19 vaccines: Global approaches in a global crisis. 18 March 2021. Accessed in Apr 2022.
[9] Holder J. Tracking Coronavirus Vaccinations Around the World. The New York Times. April 2022. Accessed in Apr 2022.
[10] WHO. The ACT-Accelerator frequently asked questions. Accessed in May 2022.
[11] Richter F. World Economic Forum (WEF). From zero COVID-19 vaccines to 11.2 billion in a year. Jan 2022. Accessed in Apr 2022.