What’s in your Blood? Molecular Analysis of the Serum Antibody Repertoire for Developing Better Vaccines and Therapeutics (50th Anniversary Lecture)

Antibodies are present in blood at high concentrations (about 10 mg/ml) and are critical for defense against pathogens. Notably, the main mechanism of protection to infection elicited by nearly all approved vaccines is the production of circulating antibodies that bind to, and neutralize the pathogen. The human immune system can generate well over 1012 different antibodies, yet only a relatively small set (which we estimate is of the order of 104 antibody proteins) are present in the blood of an individual at any time. Remarkably, more than 100 years since the discovery of antibodies, it is only possible to determine whether an individual has an antibody response to a pathogen (say, HIV or strep tests) but not the number of distinct antibodies, their amino acid sequences, relative amounts or biological functions of the pathogen-specific antibodies produced in that person.

Understanding the nature of antibodies elicited by disease or vaccination is very important for therapeutic and prophylactic purposes. We have developed a suite of proteomic, microfluidic, protein engineering and informatics technologies that has enabled the deconvolution of the identities and relative amounts of --antibodies in biological fluids and the delineation of the relationships between antibody production and the relevant B cell immunological mechanisms. This unique research toolset has enabled us to address a plethora of fundamental issues related to human health and the development of therapeutics and vaccines. Topics that will be discussed in this talk will include 1) How the antibody repertoire informs on strategies to improve the seasonal influenza vaccine 2) Identification of therapeutic antibodies directly from patients that have overcome disease 3) How is antibody immunity shaped by age and by persistent infection or inflammation