CFAR Seminar: Defining antiviral HIV-specific humoral immunity

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End Date and Time

Galit Alter, PhD

The Ragon Institute of MGH, MIT and Harvard

Location: Pelton Auditorium, Fred Hutchinson Cancer Research Center

The window of opportunity to prevent HIV acquisition is remarkably short; from the time the first virus passes through a mucosal barrier to dissemination, pointing to a critical need to contain the virus aggressively upon transmission. Thus, approaches that do not require cellular proliferation, differentiation, and homing are absolutely vital. Interestingly, the innate immune response represents our bodies first line defense against infection, and represents a remarkable arsenal of cells that are able to aggressively attack and contain most pathogens. However, due to the non-specific nature of this arm of the immune response, vaccine efforts to date have not had the opportunity to optimally harness the cytolytic power of this first line defense. The Alter laboratory focuses on defining novel approaches to harness the innate immune system to fight viral infections and other intracellular pathogens. For example, antibodies, produced by antigen-specific B cells, represent a critical bridge between the adaptive and innate immune system by providing instructions to the innate immune system on how to clear the antigen to which they are bound. These instructions are conveyed to the innate immune system through the production of specific carbohydrate structures on the constant domain of antibodies, which modulate the capacity of antibodies to engage a diverse network of receptors found on all innate immune cells. Yet, little is known about the mechanism by which antibody-glycosylation is regulated. To begin to develop new approaches to specifically recruit the innate immune system to fight viral infections, the natural dynamic variation of the glycan structure following infection/vaccination must be defined, as do the signals that regulate this process on B cells. Together, these efforts will lay the ground work for the development of next generation vaccine approaches that specifically recruit the innate immune system to enhance our ability to prevent/control HIV. Furthermore, advancing our understanding of how to manipulate the antibody glycan in a targeted manner through vaccination will also lead to the generation of vaccines with broader applications by extending to the improvement of therapeutic vaccines for the treatment of other infections, malignancies and autoimmune diseases as well.