There are also broader concerns about global equity, the speakers said. For instance, asked Baden, will the first U.S. manufacturer of a COVID-19 vaccine be expected to produce 320 million doses to cover the nation—or 7.8 billion to cover the world?

“Do we serve ourselves if we don’t protect everybody?” Baden asked.

Frahm noted that SARS-CoV-2 infections are rising in so-called low- and middle-income countries, making low-cost approaches critical for ensuring global vaccine access. Her group is working to overcome hurdles such as cost and the need to store many vaccines in refrigerators and freezers en route to communities.

“Our goal is sustainability rather than speed” to ensure that people in low-resource areas can get vaccinated, she said.

The final challenge then becomes balancing vaccine uptake—the number of people who can and choose to get vaccinated—with the effectiveness of the vaccines themselves, the speakers said.

Although an ideal vaccine would be 99 percent effective against the virus, one with less potency could still make a huge advance in the fight, said Barouch.

“Even 60 to 70 percent effectiveness could achieve herd immunity and stop the pandemic,” he said.

Public health officials could supplement a lower-efficacy vaccine with other prevention methods to maximize community protection, added Baden.

But the math only works if enough people get the vaccine, speakers said.

“Uptake matters,” said Baden. “Even if we have a 90 percent effective vaccine but only 30 or 40 or 50 percent of people use it, we still have a problem.”

Although some people cannot get vaccinated or decide not to, there are opportunities to address the concerns of those still on the fence, said Ojikutu.

“There’s room [to intervene] where people are unsure,” she said.

The road ahead

As vaccine development races onward, researchers are addressing the uncertainties that arise.

At the top of people’s minds is the question of what defines a “successful” vaccine strategy.

“Is our goal to prevent COVID illness?” asked Baden. Is it to reduce illness severity? To reduce death? To prevent infection? All of the above? More? “There are different ways to determine success,” he said.

Other questions abound:

  • Does natural immunity, acquired after SARS-CoV-2 infection, protect against reinfection?
  • Will vaccines also induce immunity? If so, what biological mechanisms will they invoke? Will different vaccine platforms work in the same way?
  • How long will a vaccine dose be effective? Will SARS-CoV-2 develop different strains, requiring a strategy akin to the seasonal flu vaccine?
  • Does a particular vaccine work differently in different populations? Will different age groups require different doses?
  • Since antibodies against SARS-CoV-2 appear to diminish after infection or illness, does that mean they continue to dwindle? Does it mean a vaccine would also quickly wear off?

That last question, at least, has a hopeful answer: A decline in antibodies is normal in the first few months after many types of infections, said Barouch.

The issue is whether SARS-CoV-2 antibodies stabilize after the initial drop and whether those remaining antibodies last a long time, he said.

“That is critical information we don’t yet have,” he said.

As these and other uncertainties swirl, it’s important to remember that “we are only months into knowing this virus,” said Baden. “Our understanding of the biology and the durability of the biology will take time.”

“There is cause for optimism, yet it must be tempered with caution,” said Daley. “Long-term, a vaccine is our best chance for ending the pandemic, but it’s unlikely to be a silver bullet for the disease itself.”

Those engaged in the fight against SARS-CoV-2 can learn from the successes and failures of past vaccines as well as from vaccine uptake campaigns, the speakers said.

In closing, Bruce Walker, faculty co-leader of MassCPR and the Phillip T. and Susan M. Ragon Professor of Medicine at HMS, reminded attendees that although treatments and vaccines offer the greatest hope for conquering COVID-19, people do not need to wait for study completion to protect themselves and others from the disease.

“There is a way to prevent infection now, today,” he said, “and that is to wear masks.”