Characterization of humoral immune responses to emerging viral pathogens

Project Abstract

Emerging viruses represent a threat to global public health, and there is critical unmet need for therapeutics and vaccines for these agents. Arthropod-borne viruses (arboviruses) are a diverse group of viruses including Zika, Dengue, Yellow fever, and Chikungunya are emerging and re-emerging viruses that continue to pose a health risk to humans. Understanding the role of the antibody response to these infectious agents will allow rational design of treatments or vaccines for use in humans. Mayaro virus is an emerging threat that has infected children and adults in South and Central America. Mayaro is transmitted to humans by the bite of the Aedes mosquitos, which have a wide geographic range highlighting the potential of this virus to emerge in a large scale similar to Zika in 2014. Mayaro virus infection is characterized by fever, headache, myalgia, rash, prominent pain in the large joints, and association with rheumatic disease as a long-term consequence of infection. The goal of the research in the Crowe lab is to identify and characterize human monoclonal antibodies from the peripheral blood of recovered patient donors. Using advanced cloning and expression techniques, we will elucidate the interaction of neutralizing (and non-neutralizing) monoclonal antibodies to Mayaro virus for their binding affinity, neutralizing potency, and protective efficacy against infectious virus in cell-based and animal based models. This work will allow development of important therapeutics and inform Mayaro vaccine design with the goal of preventing or treating infection in the regions most threatened by this emerging human pathogen.

Training Plan

The student will be supervised daily by multiple senior members of the Crowe lab, with regular (bi-weekly meetings with Dr. Crowe with the research team to allow for development and discussion of ideas, research plans, and evaluation of results and data.

Mentors

Primary: Jim Crowe