Paul Ahlquist

Keys to a successful COVID-19 vaccine

The race to develop a vaccine for the novel coronavirus that causes COVID-19 is happening with unprecedented speed, and will represent the largest global vaccination effort since the fight against polio nearly 70 years ago.

Paul Ahlquist
Paul Ahlquist

That historical perspective is important, says Morgridge virology investigator Paul Ahlquist, as a reminder of how life-changing vaccines have been for humanity. Before the successful vaccines developed by Jonas Salk and Albert Sabin in the mid-1950s, polio was one of the most feared diseases in the United States, causing an average of 15,000 cases of paralysis every year, mostly in children. It took until 1994 to eradicate polio in the Western Hemisphere.

The same trajectory existed for smallpox, a dreaded disease that killed more than 300 million people in the 20th Century alone. Three in every 10 people who contracted smallpox died from it. It took an intense eradication program, driven by effective vaccines, to eliminate smallpox in North America in 1952 and in most of the world by the late 1970s.

“People forget how much pain and suffering and death was removed by vaccines against polio, measles and smallpox,” Ahlquist says.

“At the point that a vaccine, or a pool of vaccines, has been vetted through their rigorous clinical trial processes, any risk associated with taking such a valuable protection would be vastly less than not taking it.”

Paul Ahlquist

While they are different diseases with different challenges, these successes hold powerful lessons for how we fight COVID-19 in the year ahead and how we respond to vaccines, Ahlquist says. Two of the most important elements will be patience and trust, especially in the Food and Drug Administration’s (FDA) strenuous oversight process in developing a safe vaccine.

“There are indications that there may be an unfortunate level of vaccine hesitancy,” Ahlquist says. “And we all understand this at some level –  I wouldn’t want to take one of these vaccines tomorrow. But by the time one or more of these candidates have been through the full FDA approval process, which is likely by sometime early next year, there would be strong reason to believe in its safety.”

“People should have faith in the FDA,” he adds. “Their staff know their business extremely well and they’re extremely dedicated. At the point that a vaccine, or a pool of vaccines, has been vetted through their rigorous clinical trial processes, any risk associated with taking such a valuable protection would be vastly less than not taking it.”  Moreover, he notes, even after approval, the safety of new vaccines continues to be closely monitored as their use is expanded, providing important ongoing safeguards.

Manufacturing also will be an enormous undertaking that will add further time to deliver enough vaccine for the entire population.  In addition to the hundreds of millions of doses needed in the United States alone, vaccine manufacturing is challenging because it is carried out under unusually high quality-control standards that include regular FDA inspections and testing and approval of each batch of vaccine. Ahlquist says that officials are hoping that multiple vaccine candidates will be approved for use, rather than having to rely on a single vaccine type and production pipeline. Even so, there will be a significant manufacturing lag and that may be difficult for the public to understand.

Another need for patience will come from the prioritization process for deciding what groups get the COVID-19 vaccine first, while manufacturing is ramping up, Ahlquist says. Significant national discussions of how to guide that vaccine distribution are now in progress.  Appropriately, these involve many parties, including the U.S. Centers for Disease Control, National Institutes of Health and National Academies of Sciences, Engineering and Medicine, among others, as well as substantial opportunities for general public comment.

The results should provide strong frameworks to guide policymakers in translating principles into action, Ahlquist says.  The challenge is to balance multiple justified needs in distributing the vaccine to groups including those most at risk from COVID-19, critically needed healthcare and other support personnel, targeted applications to limit pandemic spread, and others.

Another question is whether a coronavirus vaccine would require just one dose or two doses at intervals. Ahlquist says that the vaccine might well need more than a single dose to reliably generate effective levels of immunity throughout the large populations that will receive it.  Based on some characteristics of coronaviruses, it’s also possible that immunity might not be long-term, so that periodic booster shots could be needed.

“For most diseases, you would hope for an immunity that lasts for many years or even decades, but coronaviruses have a history of inducing relatively short-lived immunity,” Ahlquist says. “And so that could be an important issue in this situation; somehow the virus has evolved to be able to limit the host’s ability to protect itself. It remains to be seen if the duration of vaccine-derived immunity mirrors that from natural infection, but we may have to revaccinate people at some interval.”

The phrase “herd immunity” refers to achieving a threshold of immunity within the larger population that inhibits further spread of disease. Taking a herd immunity approach by deliberately allowing the virus to spread — a strategy floated recently by some for COVID-19 — is widely discredited by public health officials because it would inevitably lead to a markedly higher death toll. However, vaccination should provide valuable herd immunity benefits without associated deaths.

Ahlquist says he is optimistic about our potential for ending the pandemic because we have learned so much about the virus in a short time. Historically, developing an effective vaccine for a novel virus has taken multiple years, compared to a single year today. We have also identified a handful of factors — mask wearing, avoiding congregating, frequent hand-washing — that already give the population considerable protection from the virus.

Changing behavior can be an even tougher hurdle than the scientific and medical challenges, but is absolutely critical to controlling the COVID-19 pandemic. Ahlquist says that he is reminded of the HIV/AIDS crisis, where experience shows that education and behavior changes are the most accessible and effective means of preventing this deadly disease, and vastly preferable to treating people after infection.

“I’m very optimistic and hopeful that if we can just get people to recognize and practice these now well-known, readily achievable safety measures, we can largely control COVID-19 through the remaining months until vaccine options begin to be available,” Ahlquist says. “So we are not helpless. We have strong responses that will work well – we just need to practice them. And we need to stay the course, recognizing that this is our individual and collective responsibility to protect our families, communities and nation.”

Paul Ahlquist is the director of the John W. and Jeanne M. Rowe Center for Virology Research at the Madison-based Morgridge Institute for Research. The goals of the Ahlquist Lab are to increase fundamental understanding of how viruses work, to produce new ways to arrest their spread and to use such knowledge to prevent or more quickly quell future pandemics.