Up for the Challenge
As the Georgia Research Alliance celebrates 30 years, the state’s research community is attacking COVID-19 with expertise, scientific know-how and unbridled commitment.
The harsh reality of the COVID-19 crisis that hit last winter may have taken a lot of people by surprise, when something they knew only as an obscure virus in a distant part of the world changed their lives practically overnight. But Georgia’s scientific community was prepared and eager to join the fight against the pandemic that has killed or sickened millions worldwide and thousands in the state.
“They were ready to hunker down,” says Susan Shows, president of the Georgia Research Alliance (GRA), of Georgia’s top scientists, many of them brought to the state through the organization’s efforts. “They started collaborating with each other and collaborating all over the world.”
Consequently, Georgia has become a major center for COVID-19-related research, with its scientists and institutions receiving more than $120 million in grants.
“That’s new money coming to Georgia, and it’s because they have all the scientific know-how,” Shows says of the research community’s well-established reputation. “When they submitted a grant [application], people understood this is somebody very qualified and very skilled.”
Investigators at the University of Georgia (UGA), Emory University and Georgia State University are working on vaccines, in many instances drawing on their experience in studying influenza. Emory scientists are taking part in a clinical trial for a COVID-19 vaccine; researchers at Georgia State and Augusta University are actively involved in COVID testing. Morehouse School of Medicine is heading a project to promote health equity in communities hit hardest by the virus.
Much of this activity is attributable to the GRA, a 30-year-old union of government, business and academic interests that works to enhance the state’s research capability. Donations from the corporate and philanthropic communities fund the work the alliance does with Georgia research universities to establish endowed chairs and attract some of the country’s top science talents, designating them as GRA Eminent Scholars.
Most of the money for Georgia’s research comes in the form of grants from the National Institutes of Health, or NIH.
Georgia is uniquely positioned for its role in COVID-19 research, says Ted Ross, director of UGA’s Center for Vaccines and Immunology and a GRA eminent scholar. “We have some pretty high-level research institutions. We have been preparing for this type of high-level work through the actions of the GRA in bringing investigators, scientists and medical doctors to this state. We have the right facilities, the right people, all connected to business and government leaders; and it just fell into place that we would get a lot of attention from NIH, from CDC.
“There’s a lot of focus, a lot of higher-level educational institutions and medical institutions turning their attention to COVID because the problem was so acute and so immediate. I feel like for myself, personally, everything I prepared for was becoming valuable when COVID hit,” he says.
“Over 30 years,” says Shows, “we have recruited more than 100 brilliant scientists and brought them to Georgia.”
And the scientists were ready, even for something as devastating as COVID-19, she says. “They understood about SARS and some other pandemics that didn’t really affect the U.S., certainly not the way this one has. They’ve always known that those viruses – and the pathogens – are lurking out there. In their labs they’ve been dealing with [viruses, although] not in this real-time crisis atmosphere we have now.
“Seventy percent of our recruited scientists are working in the area of medical and health innovation,” she says, “and a big part of that set works in immunology and infectious diseases and virology. It wasn’t a hard pivot at all for them to say, ‘We’re going to focus on that.’”
30 Years of Discovery
The idea for the Georgia Research Alliance was born in the mid-1980s, when Georgia lost a significant research project to Austin, Texas. Civic leaders took that as a challenge to strengthen the state’s research capability, and the alliance became a reality in 1990.
The results have been nothing short of remarkable: Top scientists recruited to Georgia to do groundbreaking work that has advanced immunology, environmental research and technology. That work brings in more than $500 million annually in grants and supports the state’s reputation as a world-class research center.
“The whole concept of the Georgia Research Alliance was really a groundbreaking, novel idea to bring together government and business and academia,” says Shows, a GRA veteran who became president in September. “Business people said, ‘We need to do this, we need to invest in our research universities.’”
Ten years after it was established, the GRA started a program to help get the discoveries out of the lab and to the market. “Now we are approaching 200 companies that we have built around the discoveries at the universities,” Shows says. “They’ve produced economic results. That’s money that we wouldn’t otherwise come by. We have really built a platform for scientists to collaborate with each other – across campus lines and across disciplines.”
The alliance partners with eight public and private universities: Emory, Georgia Tech, Georgia State, UGA, Clark Atlanta University, Morehouse School of Medicine, Augusta University and Mercer University.
Next-gen Vaccines and Immunity
Currently, there are more than 250 COVID-19 vaccines in some stage of development worldwide.
In Georgia, much of the ongoing influenza research – notably, the search for a universal vaccine that protects against all strains of the flu virus – has broad and significant implications for COVID-19. Both influenza and the COVID-19 virus, for instance, are transmitted via aerosols – the droplets from sneezes, coughs or speaking.
UGA’s Ross has been working to develop a next-generation influenza flu vaccine for some 15 years. Last year, he led a consortium of investigators at 15 universities in the U.S. and Australia, including Georgia Tech, Emory and UGA, to develop what he describes as “a broadly reactive or universal influenza vaccine.” The NIH initially funded the effort with an $8 million grant. Total funding for the vaccine research and human testing could reach $130 million over seven years, which would make it the largest single award to UGA in its history.
“We’re working as a group to come up with the best vaccine candidates,” Ross says. “The intent is to change the way we do influenza vaccines in the future,” and to eliminate the need for an annual flu shot. “Our goal would be to have a long-lasting durable vaccine that would elicit protective responses for years into the future – for all the different variants of the flu virus. You wouldn’t have to take a flu shot every year; it would protect you no matter what is circulating in the population,” he says.
The work made for a natural expansion into COVID research: “Working with NIH, we have been able to now develop COVID vaccines and pair [them] with our universal flu vaccine to come up with a protective respiratory vaccine against both viruses. We are combining those together into broadly reactive flu and coronavirus vaccines – to protect us against both COVID and seasonal flu that we get every year,” he says.
The fact that the seasonal flu virus changes rapidly and the vaccine has to be re-formulated annually has been a challenge.
“Our ultimate goal would be to have a single shot that lasts you a lifetime like you do [with] polio, with smallpox, with measles or mumps,” he says. “Even if we have a vaccine you only have to take maybe every decade like a tetanus shot, that’s still a great improvement over how we do flu vaccines or even potentially a corona vaccine in the future, instead of having annual vaccinations.”
At the same time, Ross and his team are working with NIH and the National Cancer Center to assess protective immune responses to the coronavirus, to help determine how long immunity lasts in people who have been infected with the virus.
At Georgia State, Baozhong Wang, professor in the Institute of Biomedical Sciences, is also working on a universal flu vaccine. He was awarded two NIH grants last year, one for work on a self-administered microneedle patch that goes directly on the skin and delivers a vaccine by means of tiny needles that dissolve, and one that uses nanoparticles with two major flu proteins to see if they trigger broad immune responses.
“Our universal vaccine platform can be adapted for developing universal vaccines for other RNA virus pathogens, like SARS-CoV-2,” the virus that causes COVID-19, says Wang.
In lab studies on mice, Wang says, “We found our vaccines induced broadly reactive immune responses. Vaccinated mice were protected against virus challenges by different viruses.”
Next, he says, comes testing in ferrets, which have respiratory systems similar to people, and eventually human trials.
Collaboration and Challenges
Scientists working on vaccines are more collaborative than competitive, says Ross.
“We’re pretty open and communicate pretty regularly, not only in Georgia but across the United States,” he says. “Whether it’s flu or coronavirus, it’s been a very open presentation of trying to get information out to our colleagues and them to us. It’s very refreshing – there’s a little bit of a competition going on, but there’s also a great need, so to get information to everyone is critical. If somebody learns something on their end that can help everyone, then it’s really good to get that information out sooner rather than later.”
Each virus brings its own challenges. HIV, for instance, attacks the immune system, so a vaccine is “actually destroying the very line of defense that you need,” Ross says. “That’s why it’s been so difficult to make one for HIV/AIDS.” Other viruses, like Zika or Dengue or malaria, are mosquito-borne. Influenza and respiratory syncytial virus (RSV), which mostly affects children, are transmitted through the air – as is the virus that causes COVID.
In developing any vaccine, the route of infection makes a difference; so does the lifespan of the virus. For most people HIV is a lifelong infection, while flu is short-lived. It matters whether you are trying to break the method of transmission or just trying to protect the individual, Ross says.
“If I protect you from getting sick and dying that’s one thing; but if I can protect you and protect the community, that’s even a better vaccine,” he says.
The COVID Outlook
So what kind of vaccines are likely to work against COVID-19?
“Some of the big pharma companies are now focusing on the part of the virus that binds to our cells and enters our cells so the virus can replicate itself,” says Ross. “Essentially, it’s like blocking the key from entering into the keyhole of the door. Block that ability, then you can’t ever enter the room. If you can neutralize the virus from ever infecting you, that’s the best kind of vaccine to have. That bar is high. You’re never going to know for sure until you actually put it into people – a lot of people – and see if it actually reduces people’s ability to get infected.”
He understands that the process of getting vaccines from the lab to the market can seem long to the general public. “We want to make sure they are safe and they are effective. There is a lot of testing that goes on both in animals and in people before you get to put something out there on the public.
“It can seem on a day-to-day basis very slow,” he says, “but to be honest with you, there is a lot of convergence of a lot of different types of vaccines, and each of them helps the other researchers make their vaccines better.”
Emory is one of those working to speed delivery of an effective COVID-19 vaccine. It began administering doses in a Phase 3 trial at the Hope Clinic, part of the Emory Vaccine Center, in August.
“Since 2007, Emory has been part of a national network of Vaccine Treatment Evaluation Units, which test new vaccines and therapies for adults and children,” says Dr. Nadine Rouphael, interim director of the Hope Clinic and an associate professor of medicine at Emory. “So as the effort to test a COVID-19 vaccine ramped up, Emory was a natural choice to take part.”
Ultimately, hundreds of adult volunteers locally will participate in the trials at three different Emory clinics in Atlanta, including Emory Children’s Clinic.
The vaccine being tested, mRNA-1273, was co-developed by researchers at NIH’s National Institute of Allergy and Infectious Diseases and the biotech company Moderna Inc.
Emory was one of three sites in the nation to take part in Phase 1 clinical trials of the vaccine and enrolled more than 40 people. “The vaccine was generally well-tolerated and stimulated an immune response,” Rouphael says.
“In Phase 1, the main goal is to make sure the vaccine is safe,” she says. “Now, in Phase 3, we will be trying to determine if it works – meaning does it protect against COVID-19 infection. We are recruiting people who are already at risk of exposure to COVID.”
The Phase 3 study is expected to enroll 30,000 people at more than 80 sites across the country. Participants will receive either the vaccine or placebo in two shots 28 days apart.
Ross and other scientists believe there will be an effective vaccine for COVID-19 – and that it is not far off.
“The first generation of vaccines … will probably work pretty well,” Ross says, “but that doesn’t mean that there can’t be improvement. The second- and third-generation vaccines will probably be more effective than the first generation. Finally, we get to the point where we have the best vaccine that we can have.”
Yet it’s not just a matter of what happens in the lab and in the testing process.
“There are a lot of challenges with making vaccines, from the business point of view,” Ross says. “When you’ve got one you know works, you’ve got to have somebody to manufacture it. There’s got to be some way to pay for it, whether that be through insurance, through government subsidies. And that’s just for the United States.
“Think about how you’re going to vaccinate the entire world. People in different countries have different cost structures. Will they be able to afford it? How will we get it to them? Many places don’t have what we call a ‘cold chain’ – the ability to keep things refrigerated all the way from the manufacturer to the person [getting the vaccine]. Who’s going to end up paying for all of that? I don’t think those challenges have really been addressed yet. It’s just been [the idea] that we’ll have a vaccine, then poof, everything’s fine.”
Vaccination will likely require a two-dose regimen. Ross estimates that to make enough vaccine for the American population would mean almost 7 million doses. Then, there’s the rest of the world. He says these are issues that policy makers, governments and international organizations need to talk about now, while the vaccine is undergoing testing.
“If we just wait until it’s done, then it’s a long way to go to figure out who’s going to pay for it, who gets it first, versus who gets it second and third. I’m sure there are people behind closed doors having this conversation, but I’m not as confident there’s enough focus on this issue as real policy yet or a strategy to go forward.”
Boots on the Ground
While colleagues at other institutions are working on vaccines and other immunotherapies in labs, researchers at the Morehouse School of Medicine are seeking to mitigate the effects of the pandemic on vulnerable communities, to aid them in getting help – and prepare them to take advantage of a vaccine once it is ready.
Dr. Dominic H. Mack, director of the National Center for Primary Care and a professor at the school, says a three-year contract with the U.S. Department of Health and Human Services’ Office of Minority Health is funding what he calls a “boots on the ground” approach to reach those heavily affected by COVID-19, including Latino, African-American, Native American and Pacific Islander communities.
“These vulnerable populations have been badly impacted,” he says. “There needs to be a better way to communicate, educate and link these communities. We are looking at developing linguistically and culturally relevant education and training programs to reach these communities and connect to services.” That includes social services and behavioral health services as well as healthcare and COVID testing.
One of the big obstacles is an inherent mistrust that researchers must overcome. “In these communities, for historical reasons around science and health systems, they have some mistrust for the system when [it] comes to vaccines and services around COVID,” Mack says.
“It comes down to working with and empowering and giving resources to the people. You just can’t go in talking [while] you maintain all the resources. You have to show them that you respect the culture but also respect their collective intellect and how to care for their own community.” Among researchers, he says, “that can sometimes be overlooked.”
The immediate goal is to connect communities with services and try to improve COVID-19 outcomes, especially around prevention. “But the hope is to develop a sustainable model that can be agile and useful when it comes to many health issues.” One of the problems in dealing with pandemics, Mack says, “is that there is not culturally appropriate planning. We always wait until we get into the disaster or the pandemic and those same communities get left behind.”