The success of a Covid-19 vaccine will hinge on its delivery

The lesson learned from a long history of using vaccines to fight massively disruptive diseases like smallpox and Ebola is that the vaccine itself is not enough. Like a good punch line, it’s all about the delivery.

The smallpox vaccine was an average one with a limited supply. But small, dedicated teams implemented a winning strategy for it. They focused on rapidly identifying individuals with smallpox and then vaccinating people in their circle or “ring” of potential contacts, creating a cordon of immunity that kept the disease out. The same strategy was recently employed with impressive results in the fight against Ebola.

Today, all eyes are on efforts to develop a treatment to immunize people against Covid-19. And the pace of progress has been impressive. Just a few months after the disease crossed the Rubicon from bats to humans, its genetic code has been sequenced and published, diagnostic tests are available, and vaccine development is well underway. There are now many candidates at various stages in the pipeline.

Experts predict a year or more before we have an approved vaccine. Although that can seem like an eternity to many, it would be the fastest development in history.

There are many obstacles to overcome, starting with safety tests to determine that a vaccine doesn’t make the disease worse. That was a concern with a candidate developed in 2003 against severe acute respiratory syndrome (SARS), a different coronavirus. And it was an issue a few years ago with a vaccine against dengue fever.

A vaccine also must produce sufficient protection in older populations, given the age-related deterioration of the immune system, called immune senescence.

But the focus on the therapy itself can obscure complicated issues surrounding its delivery. They will be equally decisive in determining whether a vaccine can vanquish this virus.

For example, it is currently unclear how many doses will be needed to fight a disease that will have already expanded into most of the human population. The number of people who have developed natural immunity by the time vaccines arrive will determine whether we need millions or billions of doses. Rapidly producing billions of doses vastly exceeds current vaccine production capacity and would likely require costly repurposing of other facilities, or building even more expensive new manufacturing plants. Yet uncertainty about demand can make it difficult to secure sufficient investment at a fair price per dose.

Although hundreds of millions of dollars for vaccine development have already have been promised through the combined efforts of the Coalition for Epidemic Preparedness Innovation; Gavi, the Vaccine Alliance; and their partners at the World Health Organization, World Bank, UNICEF; and the Bill & Melinda Gates Foundation, the investment needed for vaccine development is $2 billion.

But investors, companies, and governments need to be assured that we will get it right — that we won’t underproduce and fall short of what we need, but also won’t over produce and waste this unparalleled investment. When a vaccine became available for the 2009 H1N1 influenza pandemic, the outbreak had ended and many doses were simply discarded.

Even if we get the vaccine we need, we mustn’t fail to get it to the people who need it. We are facing a potential shortage of health care workers to manage mass vaccination efforts, and risk increasing disease transmission by asking people to come for Covid-19 vaccination. If there are not enough doses for everyone, deciding who should get vaccinated within and across countries will need to be prioritized; although this may be a function of whether the vaccine works well enough in particular populations, such as older adults.

Communication around the vaccine’s efficacy and safety need to be carefully planned and monitored so as not fuel mistrust in a novel vaccine.

All of these challenges present an opportunity for innovation, including creating vaccine formulations that don’t require refrigeration and, better yet, are needle-free. Several years ago, the MenAfriVac meningitis vaccine was rapidly deployed to great effect in the Sahel region of Africa, in part because it could remain stable for several days without refrigeration. If we get started now, it might even be possible to develop a skin patch that could be sent through the mail and self-administered. Thinking about new ways of delivery and who can administer vaccines could help change the game.

All of these issues can be addressed, but the work must start immediately, not the day the vaccine is licensed. The keys are to:

• project demand to secure market commitments;
• develop heat-stable and self-administered vaccines;
• ensure it is effective in older populations;
• establish the capacity to track changing immunity; and
• contribute to trust in vaccines by monitoring vaccine safety after it is deployed.

The novel coronavirus is not the most aggressive pathogen that disease fighters have ever faced. But it’s fast and elusive. Our strategy for fighting it must be as novel, agile, and global as the virus itself. The battle starts in the lab, but it will be won or lost in the delivery.

Lois Privor-Dumm is the director of policy, advocacy, and communications, and director of adult vaccines, for the International Vaccine Access Center at Johns Hopkins Bloomberg School of Public Health. Naor Bar-Zeev, Ph.D., is the center’s deputy director and director of epidemiology. Maria Deloria Knoll, Ph.D., is the center’s associate director for science.