Dr. Shelly Krebs received her Ph.D. from Dartmouth Medical School within the department of Microbiology and Immunology studying virulence factors of Vibrio cholerae. She transitioned to studying HIV when she was awarded an Emerging Infectious Disease Fellowship from the CDC and APHL as a postdoctoral fellow. With interests in HIV vaccination, she performed a second postdoctoral fellowship at the Oregon National Primate Research Center using protein scaffolds to display conserved HIV epitopes as a novel vaccine strategy. She joined MHRP in 2012 to study the development of HIV-specific B cell responses resulting from different vaccination strategies. Using similar techniques, her work as expanded beyond HIV, and into studying B cell responses resulting from infection and vaccination to other emerging pathogens such as Zika, dengue, and now SARS-CoV-2.
Eliciting strong, persistent, functional antibody responses has been a major challenge for vaccine design for HIV and other infectious diseases, and the pathways that lead to durable responses remain unclear. Knowing that measuring the characteristics of antibodies alone is not enough to determine the mechanism of how functional antibodies are elicited, Dr. Krebs’s work has focused on studying the activation, differentiation and memory recall responses of antigen-specific B cells that lead to protective, durable antibodies. Understanding how individuals naturally develop effective antibody responses will lead to exploiting these characteristics in the design of immunogens for effective vaccine strategies. For example, knowing how the germline BCRs initially engage the HIV Envelope that lead to broad neutralizing antibodies has shepherded the design of immunogens capable of binding and activating these B cell lineages.
The antibody repertoire, with its exceptional diversity, provides an individual’s collective humoral response following vaccination or infection. The Krebs laboratory isolates monoclonal antibodies encoded on B cell receptors (BCRs), which provide vital information on the targeting and function the responding B cells. From the initial interaction between the antigen and the naïve B cell to somatic hypermutation in germinal centers, critical insights are gained by tracking the ontogeny of antigen-specific B cell lineages that lead to protective antibody responses. In addition, monoclonal antibodies are explored for their use as clinical tools for prophylaxis or treatment of disease.
Dr. Krebs’s research interests also include understanding the role of immune activation in disease progression. Inflammatory soluble factors that contribute to immune activation are predictive of disease progression in the absence of antiretroviral therapy (ART). However, even in the presence of ART and suppressed HIV viral load, life expectancy remains reduced compared to uninfected individuals; immune activation has been shown to be a major contributor of the increased non-AIDS morbidity and mortality. Her laboratory is interested in defining the events leading to elevated immune activation and how inflammatory soluble factors can be used to predict viral load rebound in HIV cure strategies.