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.

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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.

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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.

  • There are vaccine tablets in phase 2 trials – easier to store, no refrigeration, etc – for viral flu / respiratory infections with Covid resembling symptoms. Vaxart has oral vapendavir for Rhinovirus in phase 2b trials, and BTA585 for Respiratory Syncytial Virus RSV in phase 2 trials. A Covid-specific animal trial showed Covid antibodies in all animals, and human trials will start in June, with large Emergent Bio Solutions involved for pill production. One pill. This is the ideal delivery.

  • A closely related virus of the same family, SARS, circulated in Asia from late 2002 to mid-2003 and killed more than 700 people. They really are very similar viruses, both virulent and contagious. To stop the spread I wash my hands often, don’t go out if I don’t really have to and I wear a mask when I go out. I am looking to buy now N95 Mask somewhere. We will emerge from this pandemic, having paid a high price, battered and bruised, but more resilient and ready in the future.

  • Does anybody know why we can’t make monoclonal antibodies against Covid19’s spike protein (possibly stabilized in a miscelle) and use that to keep people alive while we wait for a vaccine? They keep talking about harvesting antibodies from recovered patients, but the logistics and effectiveness of that seems quite dubious, while monoclonal generation and production is supposed to be a fairly mature biotechnology that scales well.

    • I know some companies ARE working on that–I remember hearing Lilly in particular. But it still needs to be developed, scaled up, tested for safety & efficacy in humans… I just read an article from Forbes that said it could get emergency approval by FDA by early fall. That would be unbelievably fast, as would every other treatment that I’ve seen talked about.

  • Great job Maria and team. Would love to have a chance to talk to you about your work sometime.

  • You quote the investment needed for vaccine development as $2 Billion. How much did the US just spend on stimulus packages? Home much more is “in the works” ? And yet you seem to worry that doses may be discarded because they are not needed. To me, that would be a resounding success! Stop thinking with your wallet; people are dying.

  • Last December, very small company submitted a New Drug Application (NDA) to the FDA under standard ten month review. The product is called Qtrypta, a new application for Migraine sufferers. It has developed the ADAM, which is titanium microneedle patch coated an already approved and used drug, Zolmitriptan. This method has shown a quicker onset of the drug’s ability to reduce migraine pain. If approved, it will be the first FDA approved patch device for drug delivery.
    After Qtrypta’s approval, the ADAM can be approved by the FDA to deliver other drugs. Possibly a delivery solution for a COVID-19 vaccine.

    https://www.zosanopharma.com/technology/

    Best regards,

    • Possibly, but there’s probably going to be big differences in stability and absorption for large molecules that a vaccine is, and the small molecules that triptans are. Also, a lot of vaccines need to get into the muscle, which pretty much needs to be a needle.

  • a sad but true reflection of the human condition that an article on health is replete with financial terms, ‘costly’ repurposing,’expensive’ new plants,’fair price’ per dose etc..

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