Pandemic preparedness requires comprehensive thinking, from the earliest stages of research to enable effective development of countermeasures, to monitoring pandemic threats, and to coordination of pandemic response efforts in real-time. The time for action is during non-pandemic times, enabling a more effective response in an emergency. While this article highlights lessons specific to pandemic preparedness, many of the recommendations may also apply to local, regional, and global responses to other health emergencies, from smaller-scale disease outbreaks and biosecurity threats to weather-related catastrophes (Table 1).

Table 1 Lessons learned to improve pandemic preparedness.Lesson #1: Prioritize early-stage R&D and platform technologies

Early-stage research and platform technology approaches enable earlier access to vaccines and treatments. The biggest turning point during the COVID-19 crisis was the deployment of vaccines; and vaccines using novel platform technologies, like mRNA and adenovirus platforms, were among the fastest to be developed and authorized. Technology platforms are frameworks that allow the development of new vaccines without customizing the process, allowing for rapid production of multiple vaccines from a single system. The speed and flexibility of vaccine platforms contributed to reducing overall morbidity and mortality from COVID-19, which eventually lowered reliance on NPIs to slow disease spread35,36. The earlier a vaccine is made available in a pandemic, likely the more favorable the outcome33.

Thus, world leaders have set ambitious goals to respond more swiftly to the next pandemic. The US set goals to design, test, and review a new vaccine just 100 days after a pandemic declaration and to produce enough vaccines for the US and the world in 130 and 200 days, respectively57. Similarly, both CEPI and the G7 have initiatives that aim for new vaccines to be ready for authorization within 100 days after recognition of a pandemic pathogen58,59. Such speeds will require streamlining existing processes, like increasing collaboration and information sharing between government and industry and faster approval processes.

Crucially, the mRNA vaccines developed to combat SARS-CoV-2 were not an overnight success. Development of the COVID-19 mRNA vaccines was enabled by decades of research following the initial production of synthetic mRNA in the 1980s60,61. Equally important, advancements in carrier lipid nanoparticles enabled the delivery of mRNA to cells62. mRNA’s use as a therapeutic has been examined since the 1990s but was finally demonstrated at a global scale during the COVID-19 pandemic61. Importantly, research conducted by the US National Institute of Allergy and Infectious Diseases (NIAID) on both severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) revealed the spike protein as a target for vaccine development, allowing for rapid production of mRNA vaccines against SARS-CoV-249,58. Further research discovered that the 2 P stabilization of the spike protein was a modification that helps to stabilize the S protein in its prefusion form, which is a target for the immune response and therefore crucial for vaccine efficacy63. The fundamental role of basic research cannot be overstated. The success of the COVID-19 mRNA vaccines relied on years of progress in basic and translational research on influenza and previous coronaviruses60. Therefore, continuing to invest in basic research, as well as flexible vaccine development platforms, could help to speed response to the next pandemic58,64.

Basic and translational research must continue following COVID-19 because the next pandemic pathogen may be even harder to target than SARS-CoV-260. Ongoing research should be informed by surveillance systems that track pathogens with the potential to cause an outbreak or pandemic. Understanding vaccine targets and correlates of protection of these pathogens and generating data may provide the solid foundation of science needed for rapid vaccine development. This process requires continuous funding, yet typically, there are valleys in funding that follow high peaks during a disease outbreak or pandemic. This was highlighted by the lack of sustained, continuous investment in vaccine research following the SARS outbreak in the early 2000s, which affected the development of new vaccine technologies49. Commitments to maintain funding for vaccine research from both public and private funds—and an acceptance of funding research with a higher risk of failure, given difficult-to-target pathogens—may ensure rapid development of a vaccine when a new pathogen emerges.

Some initiatives are already committed to funding research with the aim of advancing our understanding of various virus families and developing effective vaccines. NIAID, for instance, focuses on studying potential pandemic-causing viruses, and CEPI is aiming to develop a comprehensive library of prototype vaccines against a range of viral pathogen families65,66,67. While these efforts could be complicated and slow given the range of pathogens of outbreak and pandemic potential, early-stage R&D initiatives such as these may provide enough learnings to jump-start future pandemic responses.

Further, agile vaccine technology will be critical for the response to any future pandemic due to the unpredictability of emerging pathogens. Existing mRNA vaccine platforms are highly suitable for a rapid response to an emerging pathogen given their proven manufacturing agility and scale, as demonstrated during the COVID-19 pandemic68. Typically, manufacturing can commence shortly after the antigen genetic sequence has been ascertained. This could result in both timely and effective responses to emerging threats from influenza, coronaviruses, or other pathogens with pandemic potential. Alongside an adaptable vaccine platform, research should also focus on addressing limitations in vaccine storage and distribution. For current mRNA vaccines, the requirement to keep doses frozen is a significant barrier to global distribution69. There exist goals to develop a more “ideal” vaccine, one which has a longer shelf life, extended durability, minimal dosing schedule, and wider breadth of coverage70.

Currently, efforts are also underway to apply mRNA technology to influenza following the proven success against SARS-CoV-271,72,73. But this technology may also hold promise for other endemic pathogens for which vaccines have been difficult to develop or pathogens with significant outbreak or pandemic potential74. Efforts are needed to steer research funding toward a better understanding of pandemic pathogens and vaccine targets; projects such as the WHO’s recently launched process to update their list of pathogens with pandemic potential may begin to accomplish this75.

The benefit of vaccine technologies such as mRNA relies on their “plug and play” possibilities to allow for a flexible response in the next pandemic, enabled by research identifying the most effective vaccine targets for a range of pandemic pathogens. Unlocking the potential of platform technologies will require collaboration across governments, multilaterals, academia, and industry to prioritize it. In the future, mRNA vaccine technology will be an important tool among a suite of options to respond to pandemics, one that has already been proven as an effective platform on a global scale.

Lesson #2: Bolster pandemic pathogen intelligence

Detecting novel pathogens as they arise allows for the earliest possible response, so surveillance systems should be expanded and more extensively leveraged to better detect and respond to infectious disease outbreaks in real time. Sentinel surveillance systems for global influenza—e.g., the Global Influenza Surveillance and Response System (GISRS)—were leveraged during the COVID-19 pandemic and could continue to play an important role for SARS-CoV-2 and future pathogens. In partnership with WHO, GISRS was systematically expanded to include RSV in 2015 and SARS-CoV-2 in 2020, and vitally acting as early testing centers for SARS-CoV-276. Strengthening systems like GISRS to include even more pathogens of outbreak or pandemic potential can improve future surveillance efforts. In parallel, there is a need to expand the number of surveillance sites globally; more than 70 countries still lack WHO-designated influenza surveillance centers, let alone broader systems77.

Excluding systems for West Nile virus and other arboviruses, no formal system exists to actively monitor a broad range of priority emerging and re-emerging infectious diseases, both in animals and humans78,79. For respiratory diseases, using existing influenza surveillance systems to monitor outliers of influenza-like illness (ILI) more extensively, which may encompass a range of pathogens, could also lead to earlier outbreak detection. One study speculated that if such a robust surveillance system were in use, the spread of COVID-19 could have been detected more than 13 weeks before the first reported infection peaks80. Earlier detection of SARS-CoV-2 could have led to an earlier response, potentially limiting its health and economic impact.

An expanded global surveillance system would also require investment in laboratory infrastructure, diagnostic capabilities, and workforce development at a local-, national-, and international level. Projects such as the Seattle Flu Study and the US Agency for International Development’s PREDICT may provide a roadmap. The Seattle Flu Study, launched in 2018 by the Brotman Baty Institute, University of Washington School of Medicine, Seattle Children’s Hospital, and the Fred Hutchinson Cancer Research Center, is a city-wide platform for the surveillance of respiratory pathogens, as well as pilot interventions81. This platform was used to identify the first documented U.S. case of COVID-19 community transmission in February 2020. PREDICT, which operated across more than 30 countries for a decade, worked from the ground up to strengthen surveillance for both known and newly discovered viral threats. Given lessons from COVID-19, it may also be time to experiment with new models of building surveillance systems at the local level82. Community-based surveillance, particularly in low- and middle-income countries, integrated with national and global surveillance hubs, such as WHO’s newly launched Hub for Pandemic and Epidemic Intelligence, could help drive earlier detection of emerging infectious diseases83,84.

With information on pathogens coming from surveillance systems, major public health authorities have evolved strategies to constantly evaluate pandemic risk. The CDC’s Influenza Risk Assessment Tool (IRAT) and WHO’s Tool for Influenza Pandemic Risk Assessment (TIPRA) evaluate the risk of viruses not currently circulating in humans and help to prioritize investments in pandemic preparedness85,86. For example, changes in the viral properties of a particular flu strain may signal the need to assess this strain for pandemic potential86. These tools may guide research and surveillance, while also serving as a forum to share information between scientists, public health authorities, and other stakeholders. They may also facilitate the development of pre-pandemic vaccines; this happened following the emergence of the pandemic flu strain H7N9 in 201348. As in this example, disease intelligence must be translated into action.

Furthermore, to effectively respond to newly detected disease outbreaks, sharing pathogen data is essential. Originally established in 2011, the WHO’s Pandemic Influenza Preparedness (PIP) Framework allows for pathogen samples to be shared with companies to support vaccine development. In exchange, manufacturers agree to approaches that increase access to pandemic vaccines, thereby increasing equity in the event of a pandemic87. Efforts like these lay the groundwork for data sharing in a future pandemic, but must not require additional negotiation in the event of a crisis, leading to delays in the development of medical countermeasures. For example, varied national interpretation of the Nagoya Protocol—a supplemental agreement to the Convention on Biological Diversity (CBD) that came into effect in 2014—has led to delays in sharing virus samples and subsequent manufacturing for seasonal influenza vaccines88. During COVID-19, China’s sequencing and sharing of the SARS-CoV-2 genome just days after identifying it was pivotal to successful vaccine development89. Continuous genetic sequencing of the circulating virus then allowed the detection of variants as they emerged90. Sequencing combined with surveillance may uncover the next SARS-CoV-2 variant or novel pathogen before it escalates, as long as frameworks are in place to rapidly disperse this information to the world.

On top of detection and assessment, an optimal disease intelligence system would seek to predict the next pathogen with pandemic potential. Vast amounts of existing data can be used to inform decision-making on pandemic policy and response through, for example, predictive modeling91. Other efforts are underway to use artificial intelligence to predict the next pathogen spillover event92. There is an opportunity to test new approaches to predict emerging pathogens using a range of data sources while ensuring surveillance systems focus on threats of respiratory pathogens93. Above all, sharing disease intelligence and data—quickly, in the event of a disease outbreak—can speed response to the next pandemic.

Lastly, it is pertinent to assess how to ensure prompt reactions when surveillance systems ring the alarm. In January 2020, the WHO sounded the pandemic alarm for COVID-19, yet few countries responded immediately94. Many of the calls to action by WHO were ignored, such as suggestions to quickly begin testing and social distancing95,96. These delays occurred for many reasons and varied from country to country. Some governments exercised caution to not disrupt their people’s livelihood and economy, and others lacked an understanding of the pandemic signifier itself94.

One suggested approach to kick-starting earlier vaccine development is to have a gradient of warnings that separate dangerous pandemics from more manageable outbreaks. This system, akin to the early warning systems used in healthcare and weather-related scenarios97,98,99,100, could be employed for pandemic preparedness. For instance, in healthcare settings, an artificial intelligence platform could help prioritize patients based on their medical needs, effectively managing resources during triage situations100. Similarly, a gradient-based warning system for pandemics could initiate appropriate responses at different levels of threat, with each level tied to specific actions. An early warning or Level 1 may involve increased surveillance and information sharing, while higher levels could trigger more drastic measures like regional shutdowns or global travel restrictions. Low-grade alarms may also result in more active information sharing by governments since an innocuous signal would diminish fears of causing panic and disrupting economies94. However, the success of such a system hinges on complete adherence to the rules it prescribes. An incomplete application could potentially lead to inefficiencies or confusion, but despite this, even partial application of these systems could prompt earlier responses and slow down the spread of a pandemic.

Undeniably, the evolution of disease surveillance and intelligence systems is not simple. It requires major investment and coordination across global-, national-, and local levels. The inherent complexity requires cooperation across borders, and strong leadership from global health actors given the need to quickly act and share intelligence globally. Strengthening leadership and funding at the global level may help with coordination, but countries must also commit to sustained cooperation in the short- and long-term15.

Lesson #3: Optimize and de-risk earlier pandemic interventions

NPIs saved lives but are not without limitations and consequences. Persistent long-term reliance on NPIs can be challenging because people grow tired and apathetic toward them101. Another limitation is that there may not be, or necessarily should be, a universal strategy for NPIs. Differences in NPI timing, intensity, and adherence showed varying levels of success, demonstrating the importance of geographically specific and informed NPI policies102. Research from countries that imposed lockdowns showed that while NPIs were very effective at controlling spread, they resulted in significant economic, social, and health costs26,102,103. Some consequences were clearly visible, like increasing unemployment rates from business and school closures and the spike in non-COVID-19 deaths due to the unavailability or avoidance of medical care7,26. Others, like the effect of social distancing on the mental health of children and adolescents, continue to be difficult to measure.

Beyond NPIs, early action should aim to leverage all available interventions as soon as possible in pandemic response, which may require pre-planning strategies and stockpiling a broad range of essential supplies. While leaders were encouraging social distancing early during the COVID-19 pandemic, US hospitals were already reporting shortages in basic supplies and essential medicines104. Shortages were amplified by supply chain bottlenecks, which limited access to many basic supplies, including personal protective equipment (PPE) for frontline hospital staff104. The shortage of facilities and pharmaceutical glass, especially Type I glass vials used for vaccines, also strained fill-finish capacity105. The existing fill-finish capacity shortages were further intensified by the pandemic due to a shift from vials to syringes and cartridges, increasing the demand for syringe capacity106. In response, companies reprioritized their manufacturing networks to ensure adequate production of supplies such as sterile injectables and PPE. In preparation for the next pandemic, several improvements can be made to ensure adequate supplies of essential products for healthcare systems. Governments and health systems may pre-plan access to essential medicines, hospital supplies, and treatments in anticipation of growing needs. They may also discourage the use of medical supplies, like PPE, in nonmedical settings and redirect those supplies to the most overburdened areas104.

Beyond targeted medical countermeasures, NPIs and emergency supplies represent the need to think broadly about what is needed to respond most effectively in the earliest days of the next outbreak or pandemic. NPIs will continue to be an early mainstay of pandemic response, and research has suggested interventions such as physical distancing can be cost-effective107. Additional research may inform the most timely and locally acceptable ways to roll out NPIs in the future. Furthermore, scenario planning may help pre-plan NPI strategies, as well as contents of strategic stockpiles moving forward, employing lessons learned from COVID-19.

These actions along with NPIs may significantly curb the spread of a pandemic virus, but ultimately, the earlier availability of medical countermeasures like vaccines and treatments is needed. In the time before tailor-made solutions are available, governments may utilize all available “off the shelf” solutions, including stockpiled products, to blunt the impact of disease outbreaks. WHO, for example, recommends the stockpiling of influenza antiviral therapeutics to reduce mortality in a pandemic87.

The response to COVID-19 required a rapid end-to-end response, which may again be the case in the next outbreak or pandemic. COVID-19 demonstrated the importance of diverse interventions—including NPIs and medical countermeasures—across a range of preparedness tactics, manufacturers, and product technologies to help mitigate risks. While it is impossible to predict the efficacy of any single intervention in the next pandemic, planning to employ a range of responses can guard against the risk any single intervention will not work or be available in an emergency.

Lesson #4: Sustain and leverage manufacturing capacity

New vaccines rely on manufacturers to make them. Adequate vaccine manufacturing capacity—scalable and aimed at rapid deployment—is vital. At the start of the COVID-19 pandemic, early surge capacity was inadequate to meet demand, and prior research had already predicted this would be the case108. But since 2020, manufacturers have scaled up to unprecedented capacity. The International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) estimated that worldwide vaccine manufacturing capacity would reach 12.5 billion by the end of 2021109. More recent data suggests this number will reach 20 billion by the end of 2022110.

Momentum is growing to create additional end-to-end vaccine manufacturing capacity in low- and middle-income countries111. Local manufacturing seeks to overcome barriers around unequal vaccine distribution and trade restrictions experienced during the COVID-19 pandemic. The largest barriers for new manufacturers appear to be cost and demand. Manufacturers building new facilities may need to price vaccines higher than global competitors to cover high start-up costs, and institutional buyers may need to be prepared to absorb the premium despite limited financing112. Furthermore, the sustainability of those facilities is directly tied to demand for vaccine production—if demand is limited, local production will be threatened. This has been the case for manufacturing COVID-19 vaccines in South Africa. Despite technology transfer to manufacturers for locally produced vaccines, health authorities reported limited purchasing by African countries given the availability of free doses elsewhere113.

One potential solution could be found with international organizations helping to guarantee demand for vaccines to support investments into new manufacturing. For example, the Pneumococcal Advance Market Commitment (AMC) has helped ensure access to pneumococcal vaccines in developing countries by guaranteeing a market for vaccines before development114. Another potential solution is to produce a range of routine immunizations beyond pandemic vaccines112. There are several vaccine markets that currently have high demand but a low number of suppliers, such as measles, rubella, cholera, and malaria112. The suitability of mRNA technology for vaccine development for these and many other pathogens remains unknown at this time. However, if new manufacturers produce vaccines that are needed on a routine basis worldwide, they may sustain their manufacturing capacities despite the potential for higher costs early on. But new manufacturers also need to ensure that there are buyers for these vaccines. Therefore, alone, this strategy is not enough, but with multilateral organizations like Gavi prepared to purchase from these new facilities at risk, along with other countries in the region, new manufacturers would be set up for greater success. International efforts to strengthen routine healthcare systems, including last-mile delivery of health products, and encouraging health-seeking behaviors, could help further build the demand needed to sustain local facilities.

Certain countries may also need to further develop and standardize regulatory systems surrounding medical products115. Additional regulatory expertize may be needed because many countries lack robust regulatory agencies, which may slow or limit the development of local manufacturing facilities and their approval or the acceptance of products from other countries. Multilateral organizations and governments are helping to address these challenges with the goal of ensuring biosecurity for lower-income countries before the next pandemic, though ensuring the sustainability of new manufacturing facilities is crucial.

Efforts to further localize manufacturing in low- and middle-income countries may take years to build up, so while these efforts continue to evolve, it is beneficial to sustain and use the capacity currently available. Existing facilities can be leveraged as a reliable source of production capacity in a future pandemic if it is sustained over time. Sustained capacity will require regular investments in infrastructure and operations and a trained workforce. Additionally, there will be a need for steady supplies of raw materials to support vaccine manufacturing in the event of a pandemic. Raw materials for mRNA vaccine production have been costly and scarce given the novelty of the platform. Harnessing the major benefits of an mRNA vaccine platform would therefore require careful management of raw material suppliers, at least in the near term. Establishing raw material stockpiles may prove useful in absorbing the initial need during a pandemic. With basic components in place, existing manufacturing facilities can be “warm”, primed, and ready to respond to a future pandemic. Global manufacturers have a role to play in ensuring capacity is allocated fairly, above the interests of any one country. Ultimately, international collaboration will be the key to ensuring everyone, everywhere, has access to life-saving vaccines.

Lesson #5: Troubleshoot trade, regulatory, and procurement barriers

Viruses do not have a nationality, yet vaccine nationalism—governments reserving vaccines for their own populations, leaving limited access for the rest of the world—was a pervasive problem during COVID-19. Vaccine nationalism and a lack of regulatory harmonization slowed the movement of vaccines, health products, and essential supplies across borders. Early decision-making in the COVID-19 pandemic was influenced by national interests, underscored by the uncertainty of a new outbreak. The resulting inequality of vaccine access posed a danger to all individuals as the virus spread across borders. Despite this, many high-income countries quickly developed procurement agreements for vaccines to cover their own populations. Meanwhile, COVAX, as a new organization representing many low- and lower-middle-income countries, faced challenges to begin operations