Amelia K Pinto, PhD

My research program examines how virus-specific T cell responses are generated and maintained, and how the host environment determines whether they deliver durable protection or contribute to disease. I work across virus families, including flaviviruses such as dengue, Zika, West Nile, Powassan, and St. Louis encephalitis virus, alphaviruses such as Mayaro, arenaviruses such as lymphocytic choriomeningitis virus, and coronaviruses, chosen because together they span acute, persistent, and neurotropic infection. Within these systems I investigate how the sites and dynamics of viral replication in peripheral and central nervous system tissues shape antigen availability and T cell recognition, how CD8 T cell pressure interacts with viral diversity and evolution, and how conditions at the time of antigen encounter set the quality and durability of the response that follows.

Vaccine-induced T cell immunity is a central application of this work. I define the virus-specific CD8 and CD4 T cell responses that constitute correlates of protection, with particular attention to tetravalent dengue vaccination, where cross-reactive T cell responses can protect or predispose depending on their specificity, breadth, and durability, and to emerging alphaviruses such as Mayaro, where no licensed vaccine exists and the protective target remains undefined. Across investigator-initiated and collaborative projects I evaluate how vaccine platforms and adjuvant combinations shape the magnitude, functional quality, and memory potential of the T cell response, and how those features predict protection on challenge.

A second arm of the program addresses viral infection of the central nervous system and its consequences for the CD8 T cells recruited there. Using neurotropic flaviviruses, including West Nile, Powassan, and St. Louis encephalitis virus, together with chronic lymphocytic choriomeningitis virus infection, I study how virus in CNS tissue sustains antigen presentation at vascular interfaces, how persistent stimulation drives CD8 T cells toward exhaustion, and whether that process contributes to neuroinflammation and neurodegeneration in Alzheimer’s disease. This applies the same framework I use for peripheral infection, that chronic antigen exposure and the surrounding tissue environment progressively reprogram CD8 T cells, to a setting where the consequence is neurological rather than virological.

Running through both arms is the question of how metabolic conditions, including metabolic syndrome and type 2 diabetes, alter T cell function and impair the durability of responses to infection and vaccination, contributing to poorer outcomes in affected populations. Combining immunological assays, animal models, bioenergetic profiling, and high-resolution sequencing with collaborative work in mass spectrometry, structural biology, and systems immunology, my goal is to identify the T cell correlates of protection and the mechanisms by which they fail, strengthening preparedness for current and future viral threats and explaining why some populations are poorly served by otherwise effective vaccines.