IDCRC Investigator Profile: David I. Bernstein, MD, MA

David I. Bernstein, MD, MA, is a professor in the Department of Pediatrics at Cincinnati Children’s Hospital Medical Center. His research is focused on vaccines for common infections that have significant impact on human health.

Currently, he evaluates vaccines and antivirals for herpes simplex and cytomegalovirus in pre-clinical animal models through a National Institutes of Health (NIH)-funded contract as well as industry. His clinical trials activities are performed through the NIH-funded Cincinnati Vaccine and Treatment Evaluation Unit (VTEU) and industry.

How long have you worked with a VTEU?

We were awarded our first contract in 1994, with me serving as the co-PI, and have been a VTEU since that time. I led the Cincinnati site from 1994-2020 when I turned the reins over to Dr. Robert Frenck. 

Briefly describe your background in vaccine research.

My interest in vaccines goes all the way back to my master’s thesis on rubella vaccines in 1976. After receiving my MA with Dr. Pearay Ogra, I went on to medical school, residency, and then my pediatric infectious diseases fellowship with Dr. James Cherry. During my fellowship, I performed studies on influenza vaccines and developed my interest in herpes viruses.

Using material from the first studies of oral Acyclovir treatment of genital herpes, I developed the Western blotting technique that is still used today to serologically distinguish HSV-1 from HSV-2 infections. From there, I went to Cincinnati Children’s Hospital, where I rose from assistant professor to lead the division from 2000-2010. Perhaps, somewhat uniquely, I am also heavily involved in preclinical studies of vaccines. I have led our NIH-funded contract to study herpes vaccines and antivirals in animal models for over 30 years. This combination gives me a unique perspective on vaccine development.

While at CCHMC, I also became interested in rotavirus and, with my long-term collaborator Dr. Richard Ward, began our work on rotavirus epidemiology, virology, and immunology. Again, using material from a clinical trial of a failed rotavirus vaccine, we isolated the parent virus, 89-12, that we attenuated and adapted as a vaccine candidate. We initiated the first efficacy studies of this vaccine that eventually became Rotarix™ after further development by GSK.

Briefly describe the IDCRC-supported trials you’ve supported.

I’ve been doing this for 40 years, so there are many. I have been able to continue my interest in influenza, rotavirus, and herpes viruses, including CMV, while expanding on gastrointestinal pathogens to include norovirus, cholera, and ETEC. I have participated in trials of vaccines for bioterrorism agents including smallpox and anthrax. I also expanded my research of sexually transmitted infections to include HPV and my work on respiratory viruses to include RSV, parainfluenza, parvovirus B-19, and pertussis.

For some of these agents, we developed Controlled Human Infection Models (CHIMs). These would include the first challenges with rotavirus, developing the only GII.4 norovirus challenge strain, as well as studies with cholera and influenza. We used the norovirus models to study new vaccines and provide insights into the correlates of protection.

Of these trials, what has been the most impactful or a highlight of the work?

I began studying herpes viruses during my fellowship. Therefore, the HSV and CMV vaccine studies we did are near and dear to me. The CMV trial was especially rewarding as we first identified the incidence of infection in teens and then risk factors for infection in both males and females. We used this knowledge to design and then perform a large multi-center trial of a gB subunit CMV vaccine in adolescents.

Despite this work with herpes viruses, I am probably best known for developing the rotavirus vaccine, 89-12, that became Rotarix™, the most used rotavirus vaccine globally. After a failed rotavirus vaccine trial, we followed the participants from that trial and showed that infection with the predominant circulating strain we called 89-12 was highly protective from subsequent rotavirus illness. Using similar methods to those pioneered by Dr. Sabin to develop a polio vaccine, also at CCHMC, we attenuated this strain by multiple in vitro passages. We then performed the first clinical trials in adults, older children, and then infants. Our first efficacy trials showed that the vaccine was indeed attenuated, safe, and remarkably effective. GSK then acquired the vaccine, made some modifications, and performed many large-scale safety and efficacy trials, leading to licensure around the world. The effects of Rotarix and other rotavirus vaccines in preventing severe illness and hospitalization in the USA and mortality around the world are remarkable.

What is a strength or example of the importance of the IDCRC?

The IDCRC is unique in the force it can bring to study new pathogens and evaluate new vaccines. The breadth of the talent, knowledge and experience at the VTEU sites is unmatched. We developed new capabilities and best practices when we were called upon to rapidly study the 2009 H1N1 flu vaccines. More recently, we expanded on these practices manyfold in the effort to develop a COVID-19 vaccine in an astonishingly short time. For me, this is especially amazing given that it took 20 years to license Rotarix™.

What do you like to do outside of the VTEU?

I enjoy spending time with the grandkids and watching them play football, basketball, and soccer. My favorite activity is spending time on the water whether in Destin Florida or Norris Lake Tennessee.