The time is now for committed and comprehensive action to attain more broadly protective coronavirus vaccines: The coronavirus vaccines R&D roadmap

The COVID-19 pandemic has arguably been the most devastating health event of our lifetimes. Globally, at least 6.7 million lives have been lost from SARS-CoV-2 [1], more than 10 million children have been orphaned [2], upwards of 65 million people are dealing with long-term sequelae of infection [3], and global economic growth stalled, forcing millions of people into poverty [4]. Despite this devastating toll, more than three years after its emergence in humans, the virus that causes COVID-19 continues to persist and evolve, creating a continual stream of new variants resulting in infections, complications, hospitalizations, and deaths.

Coronaviruses such as SARS-CoV-2 are constantly mutating. With every infection there is an interplay among host characteristics, past infection, and vaccination—each exerting further pressures on the virus to evolve and acquire further reproductive and fitness advantages [5]. As a result, SARS-CoV-2 variants have arisen that have shorter and shorter incubation periods, increased transmissibility, and the enhanced ability to evade protection conferred by previous infection or vaccination [6], [7]. As a consequence, we are chasing continually evolving viral opponents, leaving the global community in a reactive rather than proactive position in regard to vaccines, therapeutics, and public health policies.

Vaccines have served as the primary tool for protecting lives during the pandemic, but the ever-changing variants and subvariants have exposed the deficiencies in our current vaccine platforms and policies. First-generation COVID-19 vaccines are safe and remarkably effective at reducing serious disease, hospitalization, and death. They have served as the foundation for the pandemic response. These vaccines, however, are moderately to markedly reactogenic for some, and require repeated doses or “boosting” to maintain effectiveness. Even with boosting, they have limited ability and durability to prevent infection [8].

The most obvious challenge in a policy of repeated vaccine doses is the public’s willingness to receive additional doses. Vaccine demand has fallen substantially since the limited durability of vaccines became obvious and continued to worsen as more immune-evasive subvariants circulated. Uptake of additional doses beyond the initial primary vaccine series varies among countries, but coverage rates have generally been low and declining with each additional dose [1], [9]. For example, only approximately 15 % of eligible Americans have taken a bivalent booster, which contains an Omicron component [10]. The net result is that we continue to face continued circulation and evolution of SARS-CoV-2 viruses that mutate to evade immune responses among hosts who have partial or waning vaccine coverage, further exacerbating the situation.

Additionally, global vaccine access has been grossly inadequate, driven by the current technological requirements of SARS-CoV-2 vaccines, imbalanced global manufacturing capacity, misinformation and low uptake, and delays in the rollout of the first-generation vaccines. For example, some SARS-CoV-2 vaccines require complex cold-chain processes that are not amenable to remote or low-resource settings. Significantly, with limited and delayed efforts to enable access around the world, populations in low-income countries have less than half the rate of coverage with a single dose of a SARS-CoV-2 vaccine compared with those of high-income countries [11]. The rates of getting a full series or a booster dose are even more disparate. Given this backdrop, the current vaccine approach is unsustainable and insufficient globally.

This is a critical time for bold, committed and comprehensive action to attain more broadly protective coronavirus vaccines. We know that SARS-CoV-2 has, is, and will continue to evolve and challenge our available public health tools. The public health community can anticipate other coronaviruses, like SARS-CoV, MERS-CoV, and SARS-CoV-2, spilling over from animal reservoirs. The global community cannot afford to play reactive catch up continuously, chasing the latest variant, or expect the global population to get vaccine doses several times a year. We need better tools for reducing death and serious illness, but also new tools to prevent infection and, ideally, transmission from new and evolving coronavirus threats. This is a critical time to create and implement a new initiative to develop vaccines that give us broader protection—protection both against new variants and potentially against coronaviruses that have not yet emerged but could cause the next pandemic. Next-generation vaccines may offer additional benefits such as new methods of delivery—transdermal patches, oral or intranasal vaccines—which are easy to distribute and apply, stimulate mucosal immunity, and potentially block transmission.

1. The coronavirus vaccines R&D roadmap

The Coronavirus Vaccines R&D Roadmap (CVR) offers a clear, comprehensive, and structured plan to achieve the next level in coronavirus vaccine research and development (R&D). The plan represents a unique, proactive approach built through an interdisciplinary, cross-sectoral, and international forum of more than 50 international experts for creating a high-level research agenda with discrete goals. The CVR, developed by the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota and funded by the Bill & Melinda Gates Foundation and The Rockefeller Foundation, is a critical tool to organize, catalyze, and coordinate a complex R&D agenda for the type of vaccines the global community needs for combatting SARS-CoV-2 and the coronavirus pandemic threats of the future.

In addressing challenging, multifaceted, and interdisciplinary issues, the roadmap steers a course through a complex array of concurrent activities that are interconnected, dependent, and yet typically siloed. Governments, industry, and the research community must continue to make vital efforts to invest in R&D for broadly protective coronavirus vaccines. Political will, however, has waned for the large-scale investments essential to advance this important agenda, highlighting the need for improved advocacy and visibility. The World Health Organization and other international bodies have held meetings to discuss key topics in virology, immunology, and regulatory science. Manufacturers are working with governments to build factories and a skilled workforce. Academic and public health virologists are tracking viral evolution. A multitude of sectors and disciplines are involved in developing improved coronavirus vaccines, and they are all interdependent. The CVR recognizes and capitalizes on building bridges between these various sectors and is aimed at reducing barriers and duplication and improving efficiencies.

It is clear that an international, coordinated effort is essential to protect our global community. The early years of the COVID-19 pandemic demonstrated that a global effort and commitment is needed to ensure that people in low-resource or remote areas have access to protection offered by vaccination. Moreover, vaccine R&D cannot create optimal vaccines without structured surveillance systems and viral samples from across the world. With rapid intercontinental travel and intertwined global economies, viruses and their impact do not stop at borders; they threaten all of us.

The pandemic highlighted some inspiring examples of collaboration and sharing—from surveillance of the human population to novel data on variants. The roadmap calls for these information-sharing patterns to be systematized and formalized so that common definitions, tools, aims, study designs, and protective efficacy can be realized in next-generation vaccine development.

Planned, stepwise action will benefit our ability to protect all people against the ongoing threat of COVID-19 and likely other coronaviruses, but the effort will have even broader benefits for vaccine R&D and the vaccine innovation ecosystem for whatever future challenges we may face. Such efforts must be grounded in the best science; the roadmap outlines a plan of action that will accelerate critical and foundational research that will benefit coronavirus vaccine R&D, as well as multiple fields of health and disease.

2. Moving from planning to action

The roadmap creates an integrated, stepwise, and scientifically coherent structure to develop broadly protective coronavirus vaccines at the very time when there is a desperate need for bold, committed, and comprehensive action. The CVR represent a powerful strategy for such action, but to fully harness the roadmap as a tool, it is clear that a governance or administrative structure is needed to better coordinate a comprehensive agenda for vaccine R&D of broadly protective vaccines and to evaluate progress over time. This must include a mechanism to track progress—and accountability—on the goals and milestones that will further facilitate and accelerate this process.

Significant action is needed to ensure leadership and commitment among industry, governments, and foundations to build and sustain investment in vaccine R&D. COVID-19 has cost millions of lives and trillions of dollars. We cannot afford denial or apathy—we need to move forward with plans that make us better prepared for the next variants and the next coronavirus pandemic. The coronavirus vaccines R&D roadmap highlights the essential need for the continued investment necessary to accelerate scientific discovery, such as surveillance, animal studies, immunology, and manufacturing capacity, areas that collectively are critical for advancing future initiatives. Garnering the political will, engagement, and continued investment in vaccine R&D will be critical for true progress. A new initiative is urgently needed, and the Coronavirus Vaccine R&D Roadmap proposes and summarizes a structured plan to achieve success.

We hope the CVR will spark critical discussions and review, and that it will be widely circulated as the model we need now to protect us all later. Failure to do so will place lives and economies at catastrophic risk. No one will do this for us; we must do it together, and the roadmap provides the action steps and timelines to get us there.

Declaration of Competing Interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Hamburg reports no competing interests. Dr. Poland declares the following interests: Dr. Poland offers consultative advice on COVID-19 vaccine development to AstraZeneca, Pfizer, Medicago, Johnson&Johnson/Janssen, Novavax, and Moderna. Dr. Poland also has received grant funding from ICW Ventures for preclinical studies on a peptide-based COVID-19 vaccine for which he holds a patent. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies.

Data availability

No data was used for the research described in the article.