Stephen Crooke, Ph.D., is a postdoctoral research fellow in the Vaccine Research Group within the Mayo Clinic Department of General Internal Medicine.
As a postdoctoral research fellow in the Mayo Clinic Vaccine Research Group, my research is centered primarily around the use of systems biology approaches to develop a more comprehensive understanding of vaccine immune responses, with a secondary focus on the design and development of novel vaccines. My primary project in this latter area is focused on the use of tandem mass spectrometry to rapidly identify immunologically relevant peptides from Zika virus that can be subsequently tested in candidate vaccine formulations.
The highly publicized 2015–2016 Zika outbreaks prompted our group to consider the urgent need to design a safe, effective, and easily stored Zika vaccine. The majority of healthy people who contract the Zika virus have no symptoms or signs of infection; however, the virus can cause severe fetal brain defects when infection occurs during pregnancy—notably, the risk of defects is highest when Zika infection occurs during the first trimester. How and why Zika virus causes these birth defects is still under investigation; consequently, experimental Zika vaccines containing live virus or even whole, inactivated virus may be potentially dangerous to administer to pregnant women. Essentially, the group that most requires a vaccine to prevent infection is unfortunately unable to receive it. The increased safety profile of a peptide-based vaccine may be a game-changer in this regard. Peptide-based vaccine formulations offer a safe and effective alternative, as they do not contain live virus, do not require a cold chain for storage, and can be given to individuals of all ages—including pregnant women and those with weakened immune systems.
Building upon nearly 30 years’ worth of the Vaccine Research Group’s work in this field, our research team—led by Gregory Poland, M.D., Richard Kennedy, Ph.D., and Inna Ovsyannikova, Ph.D.—identified a significant number of candidate Zika peptides using our mass spectrometry pipeline. This approach works by first infecting cells with Zika virus and subsequently using mass spectrometry to identify viral peptides that are naturally processed by cellular machinery, giving us an idea of peptides that may be important targets for the immune response against the virus. My research has focused on evaluating the immunogenicity (ability to generate an immune response) of these identified peptides using cells from patients who have recovered from Zika infection as well as from individuals who have received experimental Zika vaccines. I presented the results of this study at the National Foundation for Infectious Diseases Annual Conference on Vaccinology Research in April, where I was selected as the winner of the Maurice R. Hilleman Early-Stage Career Investigator Award. This was an incredibly rewarding and humbling experience; I hold myself to a high standard of productivity in my research, and to have that recognized by a group of my peers was truly gratifying.
The next step for this research will be conducting animal studies to evaluate how well our peptide-based vaccine formulations protect against Zika infection. This project has the potential to inform the development of a novel vaccine candidate against Zika virus, and it is both an honor and a privilege to work with such a fantastic research team on a project that could revolutionize preventive health care for millions of people. It is truly an exciting time to be a part of the Vaccine Research Group at Mayo Clinic.