James D Brien, PhD

James Brien is an Assistant Professor of Microbiology, Immunology & Molecular Genetics, whose laboratory studies the immune mechanisms that underlie durable B cell responses and antibody mediated protection against severe viral disease, and the control of viral variants. I am very excited to join the department with great scientists, post-doctoral fellows and students. We have several projects including using our mRNA vaccine platform to understand how vaccine immunogenicity relates to correlates of protection against severe viral infection; the role of type I interferon in modulation of antigen specific B cell responses to viral infection; and how viruses evolve away from different classes of antibody responses. We study a large panel of emerging pathogens that have a global impact including dengue, Zika, and West Nile viruses. Please tell your friends and colleagues my lab is looking for enthusiastic technicians and students. When not in the lab I can be found hiking, biking or playing soccer with the family.

Dengue Virus Immunity and Vaccine Development

Our research focuses on understanding protective immune responses to dengue virus (DENV) and developing vaccines that provide safe, durable protection against all four DENV serotypes. A major challenge in dengue vaccine development is generating balanced immunity while minimizing the risk of antibody-dependent enhancement (ADE), which can increase disease severity following subsequent infection. To address this challenge, we are have developed a tetravalent mRNA-LNP vaccine encoding engineered DENV antigens designed to reduce ADE-associated antibody responses while preserving protective B and T cell immunity. Our current studies demonstrate that these vaccines elicit robust immune responses and protect against all four DENV serotypes in preclinical models. Through complementary studies in mice, human lymphoid organoids, and nonhuman primates, we are defining the mechanisms of vaccine-induced protection, optimizing antigen design and formulation, and evaluating the magnitude, breadth, and durability of immunity. Our goal is to advance a safe and effective tetravalent dengue vaccine while establishing a better understanding of the immune responses required for protection against flavivirus infection.