The coronavirus outbreak originated in China in Dec. 2019 and spread outwards, shocking the globe and the people all across it to their core. By March 2020, travel came all but to a standstill, schools started sending their students home and people across the United States started adjusting to what would be their new reality for a long time. Healthcare workers struggled as their hospitals reached capacity, elderly Facebook moms sewed handmade masks, gourmet restaurants switched to takeout and everyone downloaded Zoom.

Across the pond in Oxford, a group of leading medical researchers worked on what would soon be known as the ‘AstraZeneca vaccine.’

“The process of developing a vaccine happened … almost immediately,” Dr. Bill Hartman, director of the AstraZeneca phase III vaccine trials at the University of Wisconsin, said. “The Chinese government published the RNA sequence of the virus before the first person died of the coronavirus in China. When that happened, some of the other companies that make the mRNA vaccines, like Moderna, were able to, within a couple of hours’ time, use computer algorithms to figure out how to build those vaccines. So those were all being developed purely in real-time as the virus was just beginning to kill people.”

Fast forward to August, when students at UW received an email about a phase III vaccine trial happening on campus — sign up, and get paid $100 for each test visit for a span of two years. At universities and in major cities across the world, college students and others received the same kind of promotion — get compensated to help scientists test the AstraZeneca vaccine, the innovation that could save thousands of lives.

Only a few months after the virus’s emergence in a Chinese game market and the world had several tangible, injectable vaccines. Maybe, just maybe, the cure was in sight.

But it’s not that simple, scientists say.

“Developing a vaccine is just the first step in vaccinating the public,” UW Pharmacy professor Mary Hayney said.  “Public health officials and health care workers need to devise plans to make the vaccine available to a population of millions.”

Just working to disseminate a vaccine can take months, Hayney said. And when this disease is killing people every single day, there’s no time to waste.

As terrible as the pandemic has been, it’s brought together a concerted, interdisciplinary research effort like no other, Associate Director of the Global Health Institute Dr. Janis Tupesis said. From epidemiologists and virologists to global health practitioners, engineers, social scientists and beyond, the coronavirus pandemic has resulted in unexpected collaborations and pioneering research. The vaccine itself, while an integral part of the COVID-19 research narrative, is still only one facet in a much larger mosaic. This research started on day one and will continue for years to come.

Predicting a Pandemic

Ozughan Alagoz works in UW’s College of Engineering as an industrial engineer. Before the pandemic, he and his team applied mathematical models to important questions pertaining to logistical areas in healthcare manufacturing. But when COVID-19 hit Wisconsin, a group of researchers at UW Health recruited him to help them mitigate the spread of the disease.

For the past few months, Alagoz has spent his time creating predictive AI models that map the spread of the disease. With his models, he said he can predict the number of cases weeks into the future using a set of determining factors — and so far, his models have proven strikingly accurate.

“I developed a model that got started in like mid-March,” Alagoz said. “I was able to accurately predict the number of COVID-19 cases, hospitalizations and all sorts of things. Pretty much on a weekly basis, I was updating those projections.”

When creating these models, Alagoz said he takes things like disease contagiousness, population age structure and distribution, the extent of social distancing and travel, testing capacity and more into consideration.

But, Alagoz said he can’t predict certain aspects of human behavior. When students came back to campus in August, some of his predictions fell off because he couldn’t know whether or not students were going to social distance, or go to bars or hold large parties.

“Beginning of September, I was expecting a spike in the university population, but things went a little worse than what I was predicting,” Alagoz said. “There is a huge human behavior element. And even if you can work with experts in human behavior, it’s not easy to put that into quantity.”

When it comes to modeling what the spread might look like once a vaccine gets developed, Alagoz said this human behavior aspect introduces even more variables — we don’t yet know the vaccine’s effectiveness or how many people will choose to get it, Alagoz said.

In order for the vaccine to effectively control the disease and prevent future outbreaks, a large percentage of the population has to get the vaccine, Alagoz said. And at first, it’s likely only vulnerable populations will get the vaccine, so everyone else will have to wait another few months.

But Alagoz also said at this point, the vaccine is really the only way to truly control this pandemic in the U.S.

“Of course, if there is a vaccine, that’s the type of development that may completely transform the environment that we are living in,” Alagoz said. “If we have a vaccine, then we have a really good chance of controlling this pandemic. Otherwise — looks like that’s not going to happen anytime soon.”

Vaccine in the Vicinity

Dr. Bill Hartman got his start as a molecular biologist and anesthesiologist. After attending the University of Chicago Medical School, doing a prestigious residency at Mayo Clinic in Rochester, Minnesota and working in the field for several years, Hartman took a position as an assistant professor of anesthesiology with the UW School of Medicine and Public Health in 2019.

Not long after moving to Madison, his research focus shifted along with the rapidly changing world. As the director of the UW Health phase III trials of the AstraZeneca vaccine, Hartman works with other researchers and trial participants to test the new vaccine and determine its efficacy.

Hartman said his colleagues in Oxford, who developed the vaccine, built off existing research they had for SARS and MERS vaccines. Both SARS and MERS are coronaviruses from 2002 and 2012, respectively.

“They had a platform with which to build on for the novel coronavirus that came from Wuhan in December,” Hartman said. “They knew that spike proteins — the appendages that stick out of the virus — are important for the virus to be able to attach to cells and get into cells to cause the infection. And so the idea was to figure out how to generate antibodies to stick to those spike proteins and prevent the virus from being able to get into cells.”

Because of the existing foundation of research, the mass amounts of funding directed to the project by governments and partnerships, and the field-leading researchers in charge, the AstraZeneca vaccine was able to be developed in a much shorter amount of time than a normal vaccine, Hartman said.

But that doesn’t mean it’s risky. It’s still going through the same rigor of clinical trials as a regular vaccine would, and it will still have to reach the same standards, Hartman said.

“When we do these large scale, worldwide trials like UW is part of … you’re able to observe any effects in large groups of people, which should give you a pretty significant sampling of people in different populations all over the world to make sure that it’s safe,” Hartman said. “And each of these patients is really evaluated very, very closely. So that we know what symptoms could develop, and what we can predict will happen when people become vaccinated.”

In fact, only a few weeks after starting the trials in Madison, the vaccine trials paused to monitor abnormal symptoms in a participant in England. For those few weeks, Madison researchers couldn’t introduce anyone new to the vaccine and instead just monitored those who had already taken the vaccine.

Hartman said pausing the trials isn’t a bad thing — it happens even for minor instances, and it’s just an opportunity to fix a potential problem. In fact, the AstraZeneca trials have restarted in most trial areas outside the U.S. as of early September.

“This is a guardrail that we should be actually pretty happy about, that the system worked,” Hartman said. “So that we can assure everyone that this is being done safely, without cutting any corners.”

Aside from working as associate director of the Global Health Institute, Tupesis does work on emergency healthcare systems globally. He said the importance of an interdisciplinary approach when combatting a pandemic like this and developing a vaccine for one cannot be understated. 

For example, at the Global Health Institute, they have an infectious disease specialist who works on vaccine distribution, but also a veterinary medical researcher working on emerging diseases, a climate scientist looking at the role of the environment, a social scientist working on the safety and risk side of the issue and more. International organizations like the World Health Organization often have a similar setup when it comes to combating pandemics, Tupesis said.

“There’s no way to do this effectively if there’s not an interdisciplinary approach,” Tupesis said.

And once the vaccine gets completed, Tupesis said the challenges will extend beyond the medical sphere — leadership has to figure out how to build up an infrastructure that can create hundreds of thousands of doses and then transport them where they need to be. That’s an effort that cannot be done alone.

Secondly, Tupesis said communicating the vaccine and other kinds of necessary medical information can prove difficult.

“Some of the nonmedical challenges that we face right now are — and I’ve seen this innumerable times in emergency departments over the last six months — is that there is a divide about how willing people are to accept the medical information and the medical facts,” Tupesis said. “That’s going to be a real challenge to wage a mass vaccination campaign.”

Communicating COVID

David O’Connor is a pathologist at UW researching HIV and AIDS vaccines. While O’Connor said that vaccines inevitably come with risks — they can trigger immune responses that cause side effects in patients — large-scale clinical trials like the AstraZeneca trials minimize these risks until they’re all but moot.

The vaccine platforms that are being tested right now have shown good safety profiles in early-stage testing,” O’Connor said. “In fact, my wife and I are both volunteers in the AstraZeneca vaccine trial.”

Infectious disease epidemiologist Ajay Sethi said the key to communicating vaccine risk is to be open — hiding the science and potential risks behind closed doors won’t help anyone.

Keeping the information open and accessible also helps curb the spread of misinformation, Sethi said.

“The public should understand the FDA approval process, demand transparency of findings from phase I-IV studies, and scientists and policymakers should be clear and honest about any risks associated with vaccines that have been approved,” Sethi said. “Vaccination is among public health’s greatest achievements … Informing the public of the vaccine development and approval processes helps build trust in vaccination and an understanding of its importance to save lives.”

Like Alagoz, Hartman agreed that in order for the vaccine to effectively protect a large population, around 70% of people will have to get it.

Right now, Hartman said he’s seeing polls that around half the people in the county won’t take a vaccine even when it becomes available due to concern about potential risks. Since Hartman and others are working tirelessly to make sure their careful clinical trials span a broad audience and minimize risk as much as they can, he said communication becomes key to controlling the pandemic.

“It’s our job to prove that [the vaccine] is safe and effective, and also to convince the public that it’s safe and effective so that we can get up to that 70% threshold, so we can get as many people vaccinated as possible,” Hartman said.

Hayney, as someone who studies the effects of vaccines, said she feels it is part of her responsibility to help people understand the benefits of vaccines. She said she likes to have the opportunity to communicate with people one-on-one about vaccines in order to figure out what specific questions or concerns they may have.

Generally, Hayney said, people hesitant to get a vaccine have good intentions — they want to keep themselves and their families safe. That’s why it’s important to be compassionate and not condescending.

“One of the strategies I often take is again to ask to find out what the specific question is, and it might be more than one question, about a vaccine. And then I use the information that I know to answer that question,” Hayney said. “My strategy is that I try to make a personal connection with the patient and tell a story that says that I am invested in both my family and that patient.”

Dr. Freddy Caldera works with vaccines in immunocompromised patients, and he said one of the important things to stress is how important and how impactful having a vaccine can be for a population.

Caldera said despite some false claims made about vaccines — such as their link to autism — vaccines are overwhelmingly safe, and getting immunized benefits not just the individual, but potentially an entire population.

“This is our world without one vaccine,” Caldera said. “What makes me passionate about my work is these are real diseases. I forget what the number of people who died in the U.S. is, but there’s even a lot more people who are suffering from post-COVID issues … making sure that even once we get a vaccine that people get immunized.”

This article was updated October 14th, 2020, to reflect Dr. Hartman’s position as a professor of anesthesiology at the UW School of Medicine and Public Health, rather than at UW Health.