After the traumatic experiences of the first year of COVID-19 pandemic we now have an idea of what a world without vaccines could be like.
by Dr Alain Bouckenooghe
Thanks to the pandemic, vaccines have become part of everyday small talk. Discussing the number of shots or which brand or brands we have had, has become as common as discussing holiday plans. But just three years ago, most people in the wealthy, industrialised countries rarely even thought about vaccines let alone discussed them, or the once common diseases they protect us from.
Before the pandemic, the populations and the governments of the world’s high-income countries (HICs) had become complacent. Generations had grown to adulthood and raised children of their own without ever encountering diseases such as polio, smallpox, and diphtheria. Many thought pandemics and plagues had been consigned to the history books.
Then COVID-19 arrived and in a few short months turned the world upside down and showed us all a little of what a world without vaccines could be like.
Fortunately, thanks to herculean efforts, unprecedented levels of funding, and a little luck, vaccines were developed in record-breaking time, and the threat of COVID-19, if not eliminated, is now at least being managed. Unfortunately, that is not the case for many other diseases which are endemic in low- and middle-income countries (LMICs).
While the importance of effective, affordable, and accessible vaccines for global health security is still fresh in everyone’s minds, Hilleman Laboratories decided it was time to remind everyone that the world is still facing a vaccine crisis.
Those of us fortunate enough to live in HICs, protected by safe water, modern waste management, antibiotics, and effective vaccines, forget the immense toll that infectious diseases still take on much of the world. Every year millions of people die from infectious diseases and 94% of those infectious disease deaths occur in LMICs. Of those deaths, 46% are from diseases for which we still don’t have a registered vaccine. Shockingly, 54% of those deaths are from diseases we do have vaccines for; and people died not because there was no vaccine but because they never received the existing vaccines.1,2
Infectious diseases are endemic across large parts of the world. There are also micro-organisms with the potential to cause new pandemics; the World Health Organization (WHO) has listed priority diseases and pathogens for R&D in public health emergency contexts including Ebola, Marburg, Lassa fever, Middle East respiratory syndrome coronavirus (MERS-CoV), Nipah, Zika, and Severe Acute Respiratory Syndrome (SARS).3
Last year there was a spike in yellow fever cases with outbreaks in 12 African countries4 and the disease is also endemic in 13 countries in Central and South America.5 Globally, there are an estimated 200,000 cases of yellow fever every year, causing 30,000 deaths.6
As well as viruses there are also bacterial infections such as tuberculosis, non-typhoidal salmonella and cholera which are also endemic in many LMICs.7,8
We need to be better prepared for the next pandemic. The experts had been warning for years to expect a pandemic; that it was not a case of if there will be one, but when it will happen. So that means while we have endured a pandemic, we still need to prepare for the next one. The most likely candidates for the next, as yet unknown pandemic — what infectious disease experts call ‘Disease X’ — are probably an influenza virus or another zoonotic, bat-borne coronavirus7,9 that can spread via respiratory route. The bacterial infections I just mentioned also have potential for significantly increased public health problems. Novel species of bacteria as well as new variants of familiar more resistant species are regularly discovered.7,8
COVID-19 taught us a lot about pandemic control and vaccine development and production. Apart from the benefits of pumping lots of money into vaccine research, it highlighted two key issues which we could and should act on now.
The first was the shortfall in vaccine supply to some regions (especially LMIC), largely caused by the lack of manufacturing and logistics capabilities; in particular mRNA production facilities and the ultra-cold chain logistics facilities required by some mRNA vaccines.
Recognising the need to provide LMICs with novel vaccine technology to develop, manufacture, and distribute vaccines has led to the establishment of the Access to COVID-19 Tools (ACT) Accelerator, to improve vaccine supply and vaccination rates in countries in need. If this programme is extended to the many other unmet vaccine needs of LMICs, it could become one of the few positive legacies of the pandemic.
The importance of regional technological hubs and the sharing of mRNA vaccine technology has been recognised by the WHO. In June 2021, they announced the establishment of technology hubs to build capacity in LMICs to produce mRNA-based vaccines.10
There is also a need to develop and upskill scientists and technicians from LMICs to equip them with the skills required to run vaccine laboratories and manufacturing facilities — something the Hilleman Laboratories facility in Singapore will be supporting.
Other key issues highlighted by the pandemic is the opportunity to develop greater flexibility, innovation, and capability, in regulatory practices around the world; both to speed up the development and production of vaccines for known threats and to prepare for future pandemics.
Traditionally vaccines have gone through field efficacy studies before going into the approval process. Those studies could take five years or more. During the pandemic, the regulatory environment became less risk-averse when weighing the benefits of a vaccine against potential risks and that process was shortened.
Safety and ethical considerations must always remain paramount but we could also shorten that process for other vaccines. We should develop a more dynamic model.
We could also be more innovative in how we use safety databases, perhaps working with potential surrogate markers for efficacy. Adopting a parallel rather than the sequential model for the approval process would also speed things up. A wider understanding and adoption of adaptive trial designs could also help to reduce the time and money needed for trials compared to more traditional fixed designs because adaptive design trials are often more efficient, informative and flexible.11
In the end, getting the most shots into as many arms as quickly as possible during an outbreak is what is what we need to slow infection rates and prevent disease.12 Adopting innovative ways to streamline the regulatory process could be very helpful.
Things are improving but more still needs to be done to strike a better balance between national interests, global public health objectives, and commercial incentives. The heightened awareness of the threat microorganisms represent to public health and the economy is starting to drive such actions and has led to more funds becoming available from governments, non-profit organisations (NPOs), and private bodies.
Today more organisations are working together towards a public health vision. Philanthropic organisations are stepping in to guide and assist struggling manufacturers, by providing funding, know how, and help channel candidate vaccines for mass production. However, before manufacturing is possible, there is need to fill translational gaps, getting the product into preclinical stages and evaluating how to scale up production at the lowest cost feasible.
It’s encouraging to see manufacturing sites being developed in regions, specifically in LMIC, facing challenges with vaccine access but we still need larger regional multinational production facilities to prepare vaccines for the rest of the world. The paradigm is that each region needs to be able to stand on its own legs.
Hilleman Laboratories with its new base in Singapore, aims to both supply local needs, and be a translational space for other countries in addressing pathogens that are within the public health radar.
Once products get into the preclinical stages, there is need to plan for costly Phase II and III clinical trials in humans, before a license can be applied for. As mentioned before there is opportunity for further evolution in regulatory practices and planning of clinical trials; these could drastically help shorten a product’s ‘bench-to-arm’ timeline.
The fast production of vaccines and biologics for infectious diseases can then be further buoyed by suppliers that supply supporting materials for vaccination or treatments, such as vials and syringes. This part of the supply chain can at times become a bottle neck.
It is also important to remember that one technology cannot be a solution to developing agents targeting all harmful microorganisms. There needs to be a healthy space for innovation and continuous investigation so we may see more technologies emerge against existing pathogens and upcoming threats.
At Hilleman Laboratories, we believe the pandemic could be an inflection point for global vaccine equity. It reminded us how much the modern world needs vaccines to keep functioning, and it also showed us there are novel ways to solve the challenges we face in ensuring we all have a chance to get access to the vaccines we need.
The top three innovative COVID-19 vaccines were not developed by the multinational manufacturers that traditionally dominated the industry. Urgent need, high demand and unprecedented levels of funding committed to developing vaccines, made it easier for smaller players to enter the vaccine research, development, and manufacturing scene. The vaccine manufacturing capabilities which had developed in recent years in the global South played a critical role. Without the huge production particularly in India, but also South Africa and Brazil, there could never have been so many doses of critical vaccines produced in so short a time.
The pandemic gave the world reason to start talking about vaccines and the unprecedented global response showed us it is possible to meet vaccine challenges. Hilleman Laboratories would like to keep that conversation going and broaden it to address the many other vaccine challenges the world faces today.
That’s why we put together the white paper ‘Vaccines, Today and Tomorrow – A Review of the Global Vaccine Ecosystem and the Path to Vaccine Equity’. In it we explain how vaccines are one of the most important medical developments in history and how they have transformed the modern world. We examine the vaccine challenges we still face, not just in developing vaccines for diseases which don’t yet have them, but also in ensuring that people around the world all have fair access to the vaccines they need. Most importantly we are laying out the steps we need to take to effectively meet those challenges, and call on the world to act.
We want as many people as possibly to read the white paper and we hope it starts a new and deeper conversation around vaccines, and encourage more people to join us in calling for greater global vaccine equity.
Join the conversation today by downloading the free white paper here. [APBN]
This article was first published in the June 2023 print version of Asia-Pacific Biotech News.
References
- Global Burden of Disease, Institute for Health Metrics and Evaluation (IHME). Data accessed on 07/2020. https://www.healthdata.org/.
- Frenkel, L. D. (2021). The global burden of vaccine-preventable infectious diseases in children less than 5 years of age: Implications for COVID-19 vaccination. How can we do better?. Allergy and Asthma Proceedings, 42(5), 378–385. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677503/.
- Staff, G. B. (2022, July 11). WHO Updates Blueprint List of Priority Diseases. Global Biodefense. https://globalbiodefense.com/2018/02/12/who-updates-blueprint-list-of-priority-diseases/. Accessed 25 Mar 2023.
- Item: Yellow fever – African Region (AFRO). (2023, January 3). https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON431#:~:text=In%202022%2C%2012%20countries%20in,%2C%20Sierra%20Leone%20and%20Uganda. Accessed 25 Mar 2023.
- Yellow fever, the returning epidemic (2022, May). Pan American Health Organization (PAHO). https://www.paho.org/en/stories/yellow-fever-returning-epidemic. Accessed 25 Mar 2023.
- Yellow Fever (2018, September 14). Centers for Disease Control and Prevention (CDC). https://www.cdc.gov/globalhealth/newsroom/topics/yellowfever/index.html. Accessed 25 Mar 2023.
- White paper: Vaccines, Today and Tomorrow (2022). Hilleman Laboratories. Available at: https://hilleman-labs.org/vaccines-today-and-tomorrow/. Accessed 25 Mar 2023.
- Doron, S., & Gorbach, S. L. (2008). Bacterial infections: overview. International Encyclopedia of Public Health, 273. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7149789/.
- Wang L. Emerging Infectious Diseases Programme, Duke-NUS Medical School. Interviewed on 31 Mar 2022.
- The mRNA vaccine technology transfer hub. Available at: https://www.who.int/initiatives/the-mrna-vaccine-technology-transfer-hub. Accessed 24 Mar 2023.
- Pallmann, P., Bedding, A. W., Choodari-Oskooei, B., Dimairo, M., Flight, L., Hampson, L. V., … & Jaki, T. (2018). Adaptive designs in clinical trials: why use them, and how to run and report them. BMC Medicine, 16(1), 1-15. https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-018-1017-7.
- Reddy, K. P., Fitzmaurice, K. P., Scott, J. A., Harling, G., Lessells, R. J., Panella, C., … & Siedner, M. J. (2021). Clinical outcomes and cost-effectiveness of COVID-19 vaccination in South Africa. Nature Communications, 12(1), 6238. https://www.nature.com/articles/s41467-021-26557-5.
About the Author
Dr Alain Bouckenooghe, Head of R&D at Hilleman Laboratories, Singapore
Dr. Alain Bouckenooghe joined Hilleman Laboratories as Global Head R&D in January 2022. He has been working in the pharmaceutical industry over 20 years, mostly in vaccine R&D. As well as a Medical Degree from the Catholic University of Leuven, Belgium, he has a Master of Public Health degree from the University of Texas School of Public Health.