Dr. Deborah Fuller, is a Professor in the Department of Microbiology at the University of Washington and Division Chief of Infectious Diseases and Translational Medicine at the Washington National Primate Research Center in Seattle, WA. Dr. Fuller is an expert in nucleic acid vaccines and immunogen design with a specific focus in defining the immune responses needed for protection from viruses and tackling the challenge of making new vaccines for variable viruses such influenza and HIV and more recently, COVID-19.
HISTORIANSPEAKS: Can you tell our readers what experiences inspired you to pursue a career as a microbiologist?
FULLER: I grew up in a town 25,000 people where, for a while, our family and only one other on our block comprised the sum of Hispanics. A neighbor, just a few doors down, was the only black family. Most of the families were blue collar workers and struggled financially, especially with frequent layoffs at the factories but we were a tight community of love and strong faith. The streets were safe, and the schools were good. I emerged as a top student in our high school in math and science and I vowed to make a difference for my family, become a physician - someone they could be proud of, someone who could take care of them, especially with health care options being sparse for our demographic. In college, I discovered a love of research and during my interviews for medical school, I discovered I was more interested in understanding the cause of disease and discovering the cures rather than administering them. So, I changed my plans and went to graduate school at the University of Wisconsin where I studied the causes of infectious disease and earned a PhD in Cellular and Molecular Pathology. I then worked for over a decade at a biotechnology company in Madison, Wisconsin called PowderJect Vaccines. It was there, I become fascinated with the potential of vaccines. I learned that among all medical interventions, vaccines had the greatest impact in saving more lives than any other. Infectious diseases and pandemics will always be a threat and it was here that I dedicated myself to a career of creating new vaccines for diseases that still needed one and could meet the need for protection against a future pandemic.
HISTORIANSPEAKS: Could you describe how COVID-19 infects the body, its symptoms and effect on the body?
FULLER: There is a lot that is still unknown about COVID-19 and how it causes disease. We do know that it can transmit very easily in the air through small liquid particles (called fomites) that are released in the air when we exhale or cough and also, through contact on surfaces where these particles settle or where secretions from an infected person may stick around. Once inside the body, it gets inside our cells through a molecule or receptor on human cells called ACE2. Cells in our lung have this receptor and once inside the cell, the virus starts to replicate. Our body responds to the infection by making inflammatory responses and these responses can cause damage to our lungs leading to fluid build-up or pneumonia like disease symptoms. Fluid in the lung leads to hypoxia or reduced oxygen exchange between our lungs and blood that are critical for our organs to function. That is why patients will need a ventilator, to keep the oxygen levels up. Even as the body recovers from that, the battle isn’t over. Cells called fibroblasts come into the lung to try to repair the damage, causing fibrosis which creates another barrier to oxygen exchange between the lungs and the blood stream . The pneumonia is like drowning and fibrosis is like asphyxiation. Both conditions seriously compromise the ability of the body to get the oxygen to our vital organs. This is what is known as severe acquired respiratory syndrome or SARS. New data are also emerging that the virus also directly infects cells of other vital organs including our heart, gut or kidneys but the impact and how that manifests in the disease are still being studied. New treatments under development are aiming to not just target the virus but also our own response to it. By slowing or dampening inflammation or fibrosis, new treatments may be able to lessen the disease.
HISTORIANSPEAKS: What is the greatest challenge that COVID-19 poses to human beings?
FULLER:Currently, the biggest challenge is slowing its spread to reduce the cases of severe disease and death to a manageable level. We are trying to do this by social distancing but that is creating economic and health issues that pose additional challenges. Social distancing will not get rid of the pandemic, but it will buy time to develop testing capabilities and ultimately a vaccine. The convergence of broader testing and the development of a vaccine is what will be needed ultimately to stop the pandemic. Unfortunately, that may not happen as quickly as we hope or need. We are already seeing a push to relax social distancing measures. The greatest challenge, therefore, is to find a way to work together and consistently and hold the line together until new treatments can emerge to reduce mortality in our most vulnerable populations and until testing and vaccines can come in to stop the pandemic. With a diverse world view and economic, political and personal pressures, it is not clear we will be able to come together to meet this challenge.
HISTORIANSPEAKS: We know that African American populations have been deeply impacted by the pandemic? What role can the scientific community play in providing critical assistance?
FULLER: Social and racial inequality are already endemic in our health care systems and a pandemic will likely exacerbate this difference. As new interventions are developed, they will have limited quantities and availability and I fear it will not go out equally to those with greater need but rather to those with better access to health care. Policy makers will be the ones who can influence this the most but scientists can do their part in raising the concern and proposing new studies to determine how to make the most of these interventions based on disease rather than accessibility. It is also imperative that clinical testing is inclusive among all demographics since genetics and underlying conditions can influence outcomes of these studies. Scientists are already addressing this issue in their clinical study designs by ensuring there is broad representation in terms of gender, sex, race and age in these studies.
HISTORIANSPEAKS:What role can partnerships between governmental public health agencies, private labs, and academic institutions play in addressing pandemics?
FULLER: These groups need to come together to solve a pandemic crisis. Already we are seeing this in the scientific community with researchers quickly sharing their data and reagents to enable other scientists to turn that data into new vaccines and therapeutics. This kind of cooperation also needs to happen at the government level so that when new interventions become available, they are not treated as a political football. Already different governments are talking about how vaccine distribution will be controlled. We must remember that if there are populations without access to a vaccine, the virus, which is an equal opportunity invader, will continue to spread. So, we need to break down barriers and cooperate worldwide in both the discovery of these interventions and in their distribution.
HISTORIANSPEAKS: Are you actively involved in the race to develop a vaccine for COVID-19. What is the timetable?
FULLER: Yes, my lab is actively developing candidate nucleic acid vaccines including RNA and DNA vaccines for COVID-19 including novel designs for immunogens to include in our vaccine and delivery platforms to maximize their immunogenicity. RNA and DNA vaccines are one of the best hopes for fighting the COVID-19 pandemic and future ones. They require only the coding sequence of the pathogen and their scale-up manufacturing is quick and independent of complex cell-based processes that are required by most current vaccine strategies. We have taken a cautious approach in the development of our vaccine to first ensure the vaccine induces the right type response to provide protection while avoiding other responses that may not be beneficial. We also think it is important to test a candidate vaccine's capability to induce responses even in the aged. It is well-known that the elderly do not respond as well to vaccination but an effective COVID-19 vaccine will need to work not only in the young and healthy but also in the elderly who are among the most vulnerable in the population. We have a lead candidate RNA-based vaccine that has shown considerable promise in meeting these requirements in small animal models and is now being tested for dosing, safety, immunogenicity and efficacy in larger preclinical animal models. If our next experiments are successful, this will pave the way forward to advancing this vaccine into phase I human safety clinical trials as early as this summer.
HISTORIANSPEAKS: Why are vaccines so important in managing infectious diseases. How do they benefit the public?
FULLER: As I mentioned, vaccines are the single medical intervention that can save more lives than all other medical interventions combined. The only way to stop a pandemic is to create a world where the virus has fewer and fewer places it can go. That will only happen through the development of immunity in the population. Immunity in the population eventually occurs as people become exposed but at great cost in lives. A vaccine provides a way to induce that immunity without the risks of death and severe disease caused by an infection.
HISTORIANSPEAKS:Why does it take so long for vaccines to be approved. Why is the testing phase so rigid and lengthy?
FULLER: Key to the success of a vaccine is that it provides maximum protection with negligible risk. We are putting a vaccine into otherwise healthy individuals and we need to make sure that it works, and it is safe. Testing is rigorous because if both criteria are not met, it cannot be licensed for use. First, we need to make sure it is safe. Specifically, that it does not cause reactions or adverse effects or worse, make someone even more susceptible to infection or disease. This needs to be done not only in healthy young people but we need to test it in people with underlying conditions: the elderly, children and different races and ages to make sure it’s safe for all people and if not, to identify those people who should be excluded. Second, we need to make sure it works. Imagine putting out a vaccine that does not really work and how that would impact the spread if people are now going about their business or health care workers are treating patients thinking they are protected when they really aren’t. That cannot be. Hence, we need to test and test and test. With that said, there is a concerted effort to accelerate the clinical trials timeline. We are hearing that a process that used to require 5 years may get compressed to 18 months. How will that be possible? Clinical trials are generally completed in 3 phases, one right after another. In a compressed setting, the phases may need to overlap with the next phase starting once initial data shows that a vaccine meets primary criteria for safety and efficacy. That does not mean the safety and efficacy tests are skipped but rather, they are done in a more compressed, overlapping schedule. Another factor is prioritization of COVID19 vaccines. Each vaccine must be approved through several government agencies, but they must wait in a queue. By moving COVID19 vaccines to the front, that helps to accelerate the timeline. Still, each test needs to pass benchmarks and time will only tell how quickly we can accelerate that schedule. Two things are certain. First, the processes for development of vaccines will be forever changed by COVID19 and second, the real heroes when all this is said and done will be known as the health care workers and the clinical trial volunteers who put their own health and lives on the line for the benefit of all.
HISTORIANSPEAKS: What steps can public health agencies take in the future to protect citizens?
FULLER: We have had outbreaks of diseases in the past and major pandemics and while scientists understand the need to continue to prepare for future pandemics, we just don’t seem to learn. Once a disease goes away, the memory of it quickly fades and so do the resources and funding needed to continue to prepare for the next outbreak. We saw this recently with SARS in 2003 and Ebola, Zika and many others. Viruses will always jump from their animal reservoirs into humans for as long as humans and animals live together on this earth. It’s my hope that the lessons of COVID19 become a wake-up call to continue to maintain the scientific and public health efforts being put in place now to be able to better and more quickly respond to the inevitability of future pandemics.