White Coats: Arturo Casadevall, MD, PhD, on Developing Antibody Therapies to Treat Infectious Diseases

“White Coats” is an AABB News series that interviews the experts that are transforming the fields of transfusion medicine and biotherapies. Join AABB today to read the rest of this month’s issue.

Arturo Casadevall, MD, PhD, is a Bloomberg Distinguished Professor and chair of the W. Harry Feinstone Department of Molecular Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public Health. His research focuses on how microbes cause disease and how the immune system defends itself. In the area of biodefense, he has an active research program to understand the mechanisms of antibody‐mediated neutralization of Bacillus anthracis toxins.

Casadevall is a globally known expert in humoral immunity, molecular biology, virulence and cryptococcosis. His work has been recognized with numerous awards, including the American Society for Microbiology Founders Distinguished Service Award, the National Institutes of Health Merit Award and the Rhoda Benham Award from Medical Mycology Society of America.

Casadevall is the editor‐in‐chief of mBio, the first open access general journal of the American Society of Microbiology. He has served on numerous NIH committees, including those that drafted the NIAID Strategic Plan and the Blue Ribbon Panel on Biodefense Research. He also served on the National Academy of Sciences panel that reviewed the science on the FBI investigation of the anthrax terror attacks of 2001.

Casadevall is a member of the American Society for Clinical Investigation, American College of Physicians and the Association of American Physicians. He currently serves as the co-chair of AABB’s PLasma Antibody Network (PLAN). AABB News spoke to Casadevall about his career path in biomedical research, anti-body-based therapies and lessons learned from COVID-19.

AABB News: What influenced your career path in biomedical research?

Casadevall: When I started medical school, the problem of infectious diseases appeared to be under control. In year two, however, all that changed when the first cases of AIDS were reported. The appearance of a new lethal infectious disease that killed by destroying the immune system was previously unknown to medicine and a tremendous shock to the biomedical establishment. By the time I made it to my clinical training, AIDS was the major problem at Bellevue Hospital in NYC. The AIDS epidemic had a tremendous effect on me as we watched so many people die, and we had no effective therapy. Those experiences were major influences in my decision to pursue a specialty in infectious diseases.

AABB News: How have your research interests shaped your career?

Casadevall: My major research interest is fungal pathogenesis with a particular emphasis on Cryptococcus neoformans. My choice of working on this organism was the result of the AIDS epidemic because cryptococcal meningitis is a life-threatening disease with high mortality and morbidity in individuals with advanced HIV infection.

AABB News: You have received several distinguished awards for your groundbreaking work in the field of infectious diseases and host immunology. what accomplishment are you most proud of?

Casadevall: I am proud and humbled by all the recognition I have received. Two awards are extremely meaningful to me. In 2008, I was given the William Hinton award by the American Society of Microbiology for my efforts in mentoring scientists from underrepresented groups, and in 2022, I was elected to the National Academy of Sciences.

AABB News: Can you tell us about your development of novel therapeutic strategies for the treatment of diseases? How will these antibody therapies improve patient outcomes?

Casadevall: I have worked to develop antibody-based therapies throughout my entire professional career. Antibody therapies were first used to treat infectious diseases in the early 20th century but were largely abandoned in the 1940s with the advent of antimicrobial drugs. With the widespread development of drug resistance and the emergence of new diseases such as COVID-19, the time is ripe for the development of new antibody therapies against infectious diseases. I am hopeful that the enormous efforts made with monoclonal antibodies and convalescent plasma for COVID-19 will help bring about this development.

AABB News: You have authored numerous papers on scientific misconduct throughout your career. How did you become interested in biomedical research integrity? Can you share some of the most important (and surprising) findings from your research on this topic?

Casadevall: I became interested in the problems of science from being a journal editor. Editors have front row seats to all that is good and bad in the scientific publishing process. You see great reviewers and people who care about science. However, you also see problems in publishing, including misconduct. In 2007, I began to work on the problems of science with my fellow editor Dr. Ferric Fang. In 2012, we studied the causes of retractions and found that most were due to misconduct. This was a shock to the system because most people previously believed that error was the primary cause of retraction.

AABB News: You currently chair the national COVID-19 convalescent plasma project. What is the group focusing on now in terms of convalescent plasma therapy in immunosuppressed patients?

Casadevall: Our group is an association that began with friends coming together in March 2020. Our goal at the time was to disseminate knowledge about convalescent plasma and promote its proper use. We set up a website (https://ccpp19. org) that continues to serve as a nexus for communication and the dissemination of convalescent plasma information. We continue to meet each week at 9 p.m. EST on Thursdays. Today we work with AABB and colleagues in many institutions and countries to promote the use of convalescent plasma in immunocompromised patients. We are quite active!

AABB News: Your work was instrumental in advancing therapeutic options during the early stages of the COVID-19 pandemic. Can you share key lessons learned from COVID-19?

Casadevall: The most important lesson from the convalescent plasma effort for COVID-19 is that it is highly effective in preventing disease progression if administered early in disease using units that contain a high titer of antibody. For the past 100 years, convalescent plasma was always used emergently during infectious diseases outbreaks, such as the 1918 influenza epidemic. There was a lot of suggestive evidence that it was effective, but the data was not definitive because rigorous studies were difficult during epidemics. A good legacy of the COVID-19 epidemic is that we have learned how to use convalescent plasma effectively, and this knowledge will help us as we confront new threats, such as the next pandemic. In the first year of the pandemic, the deployment of convalescent plasma in the United States saved 100,000 lives, and that is a credit to the tremendous efforts of the transfusion medicine specialty and the blood banking field. The U.S. went from not using any convalescent plasma in March 2020 to treating more than 20,000 patients each week in fall 2020. That is a tremendous accomplishment.

AABB News: You have received recognition for mentoring scientists from underrepresented groups in microbiology. How can established scientists help underrepresented junior scientists in their career development?

Casadevall: I am extremely proud of having received the William Hinton award from the American Society of Microbiology for mentoring URM scientists. I think established scientists can help URM scientists by being supportive and good mentors.

AABB News: What is the most important research impacting your work today?

Casadevall: The tremendous technological advances made in recent years from genomic sequencing to mass spectrometry to the imaging revolution have had a profound impact on our research, allowing us to ask deeper questions on the problems of microbial pathogenesis and the mechanisms of antibody action.

AABB News: How do you spend your free time?

Casadevall: I read history, play chess (with my phone) and occasionally paint on canvas.