Antibodies constitute the fastest growing class of biotherapeutics and are invaluable as diagnostic agents.  Much more importantly, antibodies comprise the effector arm of humoral immunity in humans and animals and as such play a central role in protection against disease.  While it is straightforward to determine whether an individual has a polyclonal immune response to an antigen (e.g. ELISA tests to detect anti-HIV-1 antibodies in blood), the composition of the IgG repertoire that comprises the polyclonal response in serum or in secretions is unknown.   In fact, more than 100 years since the discovery of antibodies by von Behring (awarded the first Nobel prize in Medicine in 1901), there is no information on the number, relative concentrations and functional characteristics of the antibodies in circulation. We recently developed a suite of proteomic, microfluidic, protein engineering and informatics technologies that has enabled the deconvolution of the identities and relative concentrations of antibodies in biological fluids and also the delineation of the relationships between antibody production and B cell stimulation/differentiation.    In this presentation I will discuss how we are using these tools to address a number of important problems in medical biotechnology and human biology including:            1) Understanding of immune responses to vaccines (e.g. tetanus, seasonal flu) and how they mediate protection to antigen challenge.            2)  The evolution of neutralizing antibodies to HIV-1 in elite controllers.            3) Discovery of therapeutic antibodies by mining the serum antibody response in patients that have overcome disease.            4)  The discovery of novel biomarkers for immune pathologies.

What's in your blood? Molecular dissection of the human humoral immune response to disease or immunization

247th National Meeting (2014)

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