The Fragile Vaccine Plan to Save the World

The fast-moving partnership between governments and philanthropy merits U.S. backing.
July 29, 2020
Featured Image
National Health Institute Director Francis S. Collins testifies at a Senate Labor, Health and Human Services, Education and Related Agencies Subcommittee hearing on manufacturing a Coronavirus vaccine on Capitol Hill on July 2, 2020 in Washington, DC. (Photo by Graeme Jennings-Pool/Getty Images)

There is broad agreement that a COVID-19 vaccine is the surest route out of the present global crisis. To that end, the United States launched Operation Warp Speed to secure 300 million doses by January 2021 for domestic consumption, and the European Union, China, Russia, and some others have similar plans underway. But what about the rest of the world?

The need will be vast; the globe’s population is approaching 8 billion people, at least half of whom live in countries that are unlikely to be able to secure vaccines on their own before 2022. Pre-2017, one would have expected the United States, working with its allies, to coordinate an international response. But the “America First” Trump administration has a reflexive aversion to multilateral efforts, no matter how necessary or meritorious they may be.

With the United States on the sidelines, it has fallen to two relatively small nonprofits, working with the World Health Organization (WHO), to fill the leadership void. The plan they have assembled—the COVID-19 Vaccine Global Access (COVAX) Facility—is promising, but it depends entirely on having sufficient funds to gain leverage with potential manufacturers. The coming weeks may be decisive in determining its success or failure.

A Gates Production

Over the past two decades, Bill and Melinda Gates, working through their foundation, have become central figures in global public health. Both of the nonprofits spearheading the global COVID-19 vaccine plan are Gates endeavors.

The Coalition for Epidemic Preparedness Innovation (CEPI) was founded in 2017 with the intention of engaging governments and the commercial sector to improve readiness for a global public health emergency. Bill Gates has long been concerned that the emergence of a dangerous and contagious pathogen was inevitable at some point, and its arrival would expose a woefully underprepared world. The COVID-19 conflagration has proved him right, and has thrust CEPI’s work to the forefront of the fight against the SARS-CoV-2 virus.

The other partner is Gavi. The mission of this “global vaccine alliance” before the pandemic was to bring effective childhood vaccination campaigns to the poorest countries of the world. Gavi estimates it has prevented 13 million unnecessary deaths since its founding in 2000. COVID-19 is pushing the organization beyond its traditional role, as it is now attempting to coordinate procurement for most of the world’s nations, not just the poorest, and under a timeline of eighteen months rather than multiple years.

The COVAX Framework

For countries that commit to it, the COVAX Facility’s guarantee is the delivery of sufficient COVID-19 vaccines to protect high-priority populations by the end of 2021. More specifically, COVAX promises sufficient supply to cover the lesser of 20 percent of a country’s population, or all of its health-care workers, residents age 65 and older, and those with high-risk pre-existing conditions.

The WHO estimates this targeted population constitutes 24 percent of the global population. There are approximately 50 million health-care workers worldwide, 650 million people age 65 and older, and 1.15 billion people with significant underlying health risks.

If every country signed up with COVAX, the necessary supply to vaccinate this population would be nearly 4.3 billion doses, assuming two per person and 15 percent wastage. If countries with half the world’s population sign up, the required supply would be just over 2 billion doses, which is in line with the facility’s eighteen-month procurement goal.

CEPI and Gavi are building a large and diverse portfolio of potential vaccines candidates on the sound assumption that most of them will fail.

There are many things that can go wrong with vaccine development. A vaccine candidate might be found to be unsafe because of its harmful side effects, even if those effects are seen in a relatively small number of patients. Or it might not produce sufficient protection against the disease. Or it may prove to be too difficult to produce at scale, or too costly to deliver because of expensive shipping and storage requirements. Consequently, public health experts tend to be cautious about the likelihood of success of any one candidate, no matter how promising it might appear initially. Hence the need for a diverse portfolio.

Others analysts have made this point, but it deserves emphasis because of its importance to the design of a successful vaccine procurement plan. An example helps illustrate the point. If each vaccine candidate has a 15 percent chance of success (which is close to the historical success rate of vaccines entering human trials), a country betting on one developer would face an 85 percent probability of coming away emptyhanded. However, if a country (or a group of countries) is able to invest in 10 candidates, each also with a 15 percent chance of success, the odds of coming away with no vaccines at all would be just 20 percent. (This presumes that the vaccine candidates are sufficiently varied to prevent all of them from failing for the same reason.)

The need to enter into multiple contractual relationships with potential manufacturers is one reason that securing a COVID-19 vaccine is such a daunting undertaking. The cost and risk of committing to several developers at once, well before there is clarity on the safety and efficacy of their vaccine candidates, is prohibitive for most countries. Moreover, there is a limited supply of global manufacturing capacity, which means there is great demand for it. The United States, China, Russia, the EU and some other high-income countries have been scrambling for months to obtain pre-commitments on vaccine-manufacturing capacity for their own supplies. Countries with smaller populations do not have sufficient leverage to compete with these other procurement programs.

Push and Pull Incentives

CEPI’s role in COVAX is “push” funding, which makes it similar to the Biomedical Advanced Research and Development Authority (BARDA) in the United States. CEPI is signing contracts with developers of promising candidates to help finance the final stages of research, run clinical trials, and scale up manufacturing capacity.

To date, CEPI has agreements in place with nine developers. The portfolio includes three that also have contracts with the U.S. government (Novavax, AstraZeneca, and Moderna) and several that do not. For instance, CEPI is supporting the vaccine candidates sponsored by the University of Queensland in Australia, Clover Biopharmaceuticals, and the partnership of the University of Pittsburgh, Institut Pasteur, and Themis Bioscience.

CEPI’s “push” is expected to work in concert with a “pull” from Gavi. In an ongoing pneumococcal vaccination campaign, Gavi has secured large supplies through advance market commitment (AMC) contracts with manufacturers. With AMCs, Gavi promises vaccine sponsors that it will purchase a certain number of doses, at a predetermined price, if the sponsors can clear all of the necessary regulatory hurdles. Without such a guarantee, manufacturers may be reluctant to take on the substantial risks that accompany vaccine development.

Gavi is now trying to assemble the financing from participating countries and donors to enter into AMCs with many of CEPI’s COVID-19 vaccine partners, and possibly other manufacturers as well—a plan that requires $18.1 billion, per a WHO estimate. As of late June, only $3.4 had been committed to COVAX and related efforts on expanded testing and therapeutics. The United States, China, Russia, and India have all declined so far to support the plan, and even the countries that have made commitments have contributed sums that are well below what will be required to make the vaccine facility a powerful force in the rapidly evolving COVID battle.

The Fine Print

COVAX is the only real hope of securing vaccines over the next eighteen months for a large number of nations. The countries with the lowest per capita incomes have no other realistic options and will benefit substantially from subsidization of their procurement requirements. Other middle-income countries also will benefit from a coordinated international plan, even without subsidization, because their populations are too small to secure bilateral deals with a diverse array of manufacturers. Their best option is to combine forces with other countries to improve their leverage in the global marketplace.

COVAX is potentially attractive to some high-income countries too, but it comes with strings attached.

On their own, countries such as the U.K., Japan, Canada, and Australia are perfectly capable of securing deals with the big players in the biopharmaceutical industry, and especially from their domestic companies. Indeed, several promising vaccine candidates are based in these locations. For instance, the U.K. has supported the Oxford-AstraZeneca effort and will be first in line for vaccines if and when it is approved for use.

Still, promising as the Oxford vaccine looks at the moment, there is no guarantee it will work when administered to large numbers of patients. And if it doesn’t, the U.K. will need other options, which is why it recently signed agreements with two other manufacturers and has also expressed interest in the COVAX Facility.

Even so, advanced-economy countries see COVAX as a second-best option because it implies large numbers of lower-risk residents going unvaccinated all the way through 2021. The COVAX Facility’s goal is only to vaccinate high-priority groups by the end of next year based on a principle of fair and equitable access. Whatever supply the facility procures will be distributed first based on vaccinating these populations in all COVAX-participating countries. Only then will supply go to lower priority groups, and distribution will be based on population size, not ability-to-pay. In other words, it could take multiple years for countries relying exclusively on COVAX to vaccinate their entire populations, which is a timeline that residents in the developed world are likely to find disappointing, and possibly intolerable.

The U.S.’s Opportunity

Although the Trump administration is unlikely to see it this way, the CEPI-Gavi vaccine program could be an era-defining opportunity for the United States. The world has not faced a crisis of this severity in many decades. The situation cries out for a coordinated plan that harnesses global expertise and manufacturing capacity to deliver a solution as rapidly as possible, and not just for rich countries. The United States would enhance its prestige if it led the development and execution of a plan that freed all of the world’s nations from the grip of this pandemic.

That is an achievable objective if Operation Warp Speed were to work in tandem with CEPI-Gavi endeavor. Operation Warp Speed’s goal is 300 million vaccines by January 2021, and while nothing is assured, there are promising candidates that may allow the United States to overshoot this goal, if not by January then perhaps at some other point early in 2021. Working with the EU, the U.K., Japan, and other allies, the United States should develop a vaccine commitment program that ensures any excess supply secured by these high-income democracies is shared rapidly with the COVAX Facility, perhaps even simultaneously with domestic deliveries. This commitment need not conform perfectly to the WHO goal of “equitable access” to be seen by COVAX-participating countries as a welcome source of support.

Short of leading a coordinated international response, the United States could provide financial backing to COVAX, which is the route Senate Republicans are recommending in their latest COVID relief legislation. A provision in their proposed bill would appropriate $3 billion to Gavi’s COVID vaccine-procurement program. The final bill must be negotiated with congressional Democrats.

An effective global vaccination program serves U.S. interests beyond its reputational opportunity. Proponents of a multilateral plan often note that COVID-19 is a global problem requiring a global solution, and while that formulation risks descent into cliché, it is also true. If the virus is allowed to circulate the globe unchecked, there is a risk that it will mutate and require additional rounds of vaccination to prevent further epidemics, including in the United States. Further, the longer the current pandemic goes on, the more damage it will cause to global economic growth, which will suppress incomes in the United States and other advanced economies.

The entire world is anxiously awaiting news that safe and effective COVID-19 vaccines are on the way. The CEPI-Gavi effort increases the chances that such vaccines will reach half of the world’s population, if it is given the support it needs to work. The United States has within its power the ability to support the COVAX Facility without undermining U.S. domestic goals. It is plainly in our interests to do so.