Researchers have unlocked vaccines for coronavirus at an unprecedented pace, but COVID-19 has managed to stay a step ahead.
On Jan. 29, pharmaceutical giant Johnson & Johnson unveiled a vaccine that is less difficult to distribute than others. It is a single shot that only needs a normal refrigerator — practically roughing it compared to the elaborate cold-chain technology that Pfizer’s two-dose vaccine demanded a month earlier.
This latest vaccine underwent trials with nearly 44,000 people in the United States, Latin America and South Africa, all places where the virus had run wild for months and easily transmissible variants had been detected. In the U.S., the new vaccine was 72 percent effective, but in South Africa, where a more potent variant had taken shape, researchers found the same vaccine prevented infections in a smaller percentage of volunteers — 57.6 percent — during clinical trials. The data raised alarm bells about how much protection these new vaccines might afford and what else might need to be done.
Drugmakers are exploring how to tailor vaccines more narrowly to these mutants, but modifying existing vaccines is not as easy as flipping a switch. The decision sets into motion questions and concerns about manufacturing logistics, regulatory hurdles and distribution bottlenecks that have stymied the United States’ response throughout the COVID-19 pandemic.
Viruses mutate to stay alive. The more times a virus spreads — or replicates — the more opportunities there are for random evolutionary accidents in its genome. Any change could either doom the virus or play to its advantage, said Dr. Angela Rasmussen, a virologist at the Georgetown University Center for Global Health and Security.
Right now, three notable COVID-19 variants appear to be transmitted more easily than other strains of virus, and threaten to frustrate efforts to contain the pandemic and get life back to normal. The Centers for Disease Control and Prevention has confirmed that cases of B.1.1.7 from the United Kingdom, B.1.351 from South Africa and P.1 from Brazil have have all been found in the U.S., and it is likely that more variants exist but haven’t been detected yet, CDC Director Rochelle Walensky said during a recent White House COVID-19 briefing.
Scientists say it’s far better to be vaccinated and have evidence-based protection against the virus than to skip your turn and gamble with your health. But so far, the nation’s efforts to monitor the virus remain woefully inadequate when it comes to capturing the true volume of new infections and tracing exactly how the new variants are moving within the population — lingering consequences from the Trump administration’s disorganized response to the pandemic. Vaccine distribution has also lagged, though it is picking up pace, according to Tim Manning, the national supply chain coordinator for the White House COVID-19 Response Team. But while experts figure out how to catch up to the virus and the country waits, there are already steps being taken right now to buy more time.
The hurdles of changing a vaccine
According to the CDC, more than 59 million doses of the approved vaccines have been distributed, and roughly 42 million doses have been administered — almost 13 percent of the U.S. population, without taking into account that no vaccine yet has been approved for pediatric use. Experts estimated that if about 70 percent of the country gets vaccinated or immunized against the virus, then it may be possible to slow or stop its spread
The vaccines from Pfizer and Moderna that are currently being used around the country were shown in clinical trials to be more than 90-percent effective in preventing infection, according to data the companies submitted. Those trials wrapped up before the most recent variants revealed how much of a threat they could become, so there’s not enough data (yet) to determine the vaccines’ effectiveness against these variants.
These vaccines can be quickly tweaked, said Dr. Drew Weissman, a physician and infectious disease expert at the University of Pennsylvania. The genome for SARS-COV-2 maps out the sequence of proteins that form the virus. The mRNA vaccines are short segments of the viral genome, so if the virus changes at all, researchers can swap out proteins to mimic those evolutionary adaptations. For 15 years, Weissman worked with biochemist Katalin Kariko to develop the research and technology for the mRNA vaccines, which have been vital in fighting the virus.
It would take six weeks for researchers to go from “plugging new variants into the vaccine” to “make a new vaccine ready to go into people,” he said, but that does not account for the time it would take to have a drug approved. Weissman compared the process to the way the vaccines for the seasonal influenza are modified each time it circumnavigates the globe.
But while that analogy might work in terms of the science, the regulatory process is not likely to be the same. Flu vaccines have been used for more than four decades on hundreds of millions of people and they don’t require full-scale clinical trials to earn FDA approval each year. We don’t have that kind of history with coronavirus vaccines yet, said Dr. Jesse Goodman, former chief scientist at the FDA and professor of medicine and infectious disease at Georgetown University.
But Goodman said he thinks the FDA “can find a pathway.” The way he sees it, there are at least three options:
- Identify a dominant variant and produce a vaccine that targets one.
- Design a booster for people who have already been vaccinated that improves their immune response to the new variants.
- Produce vaccines that offer protection against multiple variants.
The two vaccines that already received FDA authorization have already undergone “pretty rigorous trials,” Goodman said. In the months since they were permitted for emergency use, both of those vaccines have been tracked closely and regulators appear to be increasingly comfortable with what they have seen so far, he said. He said that one approach could include designing a vaccine that targets a particular variant and gathering data on its effect on “several hundreds of people” in a study that is comparable to the phase 1 or phase 2 clinical trials. If granted an EUA, Goodman said, “You could envision them being rolled out, and perhaps more data being collected.”
“You want to make sure that if you do give it to people, it’s going to be protective,” he said.
Based on how the mRNA vaccines are designed, the process of changing them “is much more straightforward” than using a weakened version of a virus to trigger and train up the body’s immune response, as is the case with vaccines for measles and chickenpox, said Dr. James Hildreth, president of Meharry Medical College, who sits on the FDA’s committee that has reviewed data on COVID-19 vaccine safety, effectiveness and appropriate use. But the bigger question is whether or not the FDA will require new rounds of clinical trials after these changes are made to authorize updated vaccines for public use.
“There’s no reason to expect that the safety profiles would be different for the two (EUA vaccines) if the modifications are minor, if there are one or two changes in the sequence,” Hildreth said.
But he said the sequence would still be a new one, and without data documenting its safety and efficacy, he said “it would be hard to be definitive” in knowing how the human body might respond once injected with any modified vaccines. Data from earlier trials might be helpful in figuring out how to safely tweak already approved vaccinations to better combat variants, Hildreth said.
AstraZeneca’s two-dose vaccine does not use mRNA, and it has not yet been approved for use in the U.S. On Sunday, South Africa paused its plan to begin vaccinations because the AstraZeneca vaccine was not found to offer “minimal protection” against mild and moderate cases of the virus, BBC reported, which added that the new variant accounts for almost all new COVID-19 infections in the country. The pharmaceutical company has said it will develop a modified version, but that won’t be ready until autumn, according to company officials.
Dr. Tom Frieden, former CDC director, said that new regulatory pathways outside of an EUA must be considered and must be “thought through openly” to avoid fracturing public trust about the process. Especially in communities of color, a history of systemic racism and abuse in health care have fueled distrust of the medical community. Public health needs to lean on trusted messengers to promote the continued need for vaccination, Hildreth said.
“As more people get the vaccine, some of those who are hesitant are realizing it’s OK,” he said.
Considering how vaccines may need to adapt to COVID-19, Weissman urged the public and researchers to take a long-term perspective and strategy. Over the past two decades, he said the world has hosted three (far smaller) coronavirus epidemics.
“You have to assume there’s going to be more,” he said. “Once we’re done with COVID-19, there’s going to be some other coronavirus epidemic at some point in time.”
Rather than let the globe be caught off guard all over again, Weissman said researchers should explore more comprehensive strategies to beat back runaway viruses. He said he is working with a team of researchers to develop a pan-coronavirus vaccine. If that can be created and ready the next time a viral outbreak is detected, Weissman said, “We can stop the pandemic before it starts.”
What else public health can do
To Rasmussen, this moment serves as a warning about letting COVID-19 spread out of control and a reminder to approach the pandemic more aggressively.
“It doesn’t mean vaccines are hopeless, and we’re doomed to an eternal pandemic,” she said. “It’s even more important to vaccinate as many people as quickly as possible.”
But “Vaccination alone is not going to get us out of this,” Frieden said.
Months before any vaccines were available to the public, New Zealand squashed the coronavirus by supporting scientists to guide the nation’s response, entering lockdown for several weeks. and using contact tracing as cases shrank.
Even with the emergence of variants, that success is still possible in the U.S., Rasmussen said. While more transmissible, the variants rely on the same methods to infect new hosts. That means we already have the tools we need to stop them, she said, like masks, avoiding crowded spaces and getting tested and isolating if you feel sick.
“This is the home stretch,” she said. “If people can just grit their teeth and get through this, the sooner more people do that, the sooner we’re going to be able to relax and cross the finish line.”
During his first days in office, President Joe Biden signed several executive orders to strengthen the nation’s collective response to the virus, giving state and local health departments more support to fight the pandemic and offering more public transparency through regular press briefings. On Tuesday, Andy Slavitt, the White House’s senior adviser to the COVID-19 response team, tweeted that the Biden administration increased vaccine shipments to states by 28 percent after three weeks in office.
Another option is for the Biden administration to more fully deploy the Defense Production Act, a way to prioritize supplies and resources needed to ramp up enough testing materials, personal protective equipment and vaccines, he said. One benefit of using this tool could allow Pfizer to accelerate vaccine production, Slavitt said.
The Biden administration’s “all-of-the-above approach” of encouraging more face masks, less travel, better access to testing and faster distribution of vaccines is needed right now because the U.S. has languished during the pandemic for so long, Frieden said. But these new variants are the pandemic’s wild card, he said. To keep them at bay, all of these strategies must be ratcheted up.
“This is going to take months to turn around, not days,” Frieden said.