Scott A. Smith, MD, PhD, an assistant professor in the Division of Infectious Diseases at Vanderbilt University Medical Center, is this year's recipient of the Pfizer Young Investigator Award in Vaccine Development. This award provides funding for outstanding research in vaccine development, either through clinical or laboratory investigation, to a candidate who demonstrates commitment to a career in vaccinology.
Dr. Smith obtained his PhD in microbiology and immunology at the University of Louisville in 2002. He studied viral pathogenesis, focusing on proteins encoded by poxviruses used to modulate the host immune defense. After completing his dissertation, Dr. Smith continued post-doctorate work at the University of Louisville while attending medical school. He received his MD in 2006, then entered the American Board of Internal Medicine research pathway at Vanderbilt University Hospital, completing his residency in internal medicine, followed by fellowship in infectious diseases. During this time his research interests began to focus on vaccine development as he started exploring new strategies for developing vaccines against emerging and neglected viral infectious diseases.
Throughout the research years of his infectious diseases fellowship training, Dr. Smith worked to improve our understanding of the antibody response to natural dengue virus infection. He enhanced the efficiency and versatility of human hybridoma generation for use as a tool to analyze the humoral immune response to infection or vaccination. By studying hundreds of human monoclonal antibodies, Dr. Smith dissected the protective and pathogenic anti-dengue virus antibody response. The molecular information that was obtained is now being used in the rational design of dengue vaccines that aim to enhance the induction of protective neutralizing antibodies and reduce the risk of development of severe disease.
Chikungunya virus has reemerged and caused extensive outbreaks across Africa, India, Asia, and more recently Europe. The first outbreak of chikungunya in the western hemisphere is ongoing throughout the Caribbean. Although the acute illness is associated with a low mortality, significant morbidity results from incapacitating polyarthralgia. Currently there are no approved antiviral medications or vaccines available for prevention or treatment of chikungunya. A live attenuated vaccine was developed, but trials were halted due to induction of arthralgia. Alternative vaccine strategies have been under investigation as the fear that a live chikungunya vaccine might induce chronic rheumatism remains. A better understanding of hte humoral immune response to natural chikungunya virus infection is first needed before effective vaccine design can proceed.
Dr. Smith has proposed to generate a novel panel of naturally occuring human anti-chikungunya virus monoclonal antibodies to dissect the determinants of human antibody-mediated protection, fully characterizing each potently neutralizing antibody both functionally and genetically. He plans to use this information in conjunction with vast repertories of antibody variable chain sequence data, generated in parallel using deep sequencing, to determine the genetic and structural basis for variation in affinity, specificity, and functional activity. The goal is to use such molecular information for the upcoming structure-based design for an effective chikungunya vaccine that could enhance the induction of protective neutralizing antibodies while reducing the potential risk for the development of polyarthralgia.
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