Director, Scripps CHAVD & Chair, Department of Immunology and Microbiology
The Scripps Research Institute, Department of Immunology and Microbiology, 10550 North Torrey Pines Road, IMM-2 La Jolla, CA 92037
In his career, Dr. Burton and his lab discovered the prototype broadly neutralizing antibody to HIV, expanded the availability of bnAbs with the discovery of the PGT bnAbs and showed the structural basis of virus recognition by bnAbs that is crucial for bnAb-based vaccine design.
Dr. Burton and his laboratory have contributed to multiple aspects of vaccine development.
A key contribution is related to the identification of the effector function sites on the antibody molecule — in 1980, Dr. Burton proposed the location of the first antibody effector site that complements C1q. The identification of the site at the mid-point of the antibody Y-shaped molecule is important in allowing the antibody molecule to bring target and effector cells into close proximity. These early studies form the basis for modern-day engineering of antibodies for enhanced effector function, which became important in therapeutic antibodies in the clinic.
Dr. Burton also developed phage libraries that generate human antibodies to a range of infectious agents, including HIV, Ebola virus and hepatitis C virus. The Burton lab isolated the first human monoclonal antibodies by this route and went on to show that a diverse array of human antibodies against a panel of pathogens could be cloned from a single individual.
In addition to these contributions, Dr. Burton isolated and characterized broadly neutralizing (bn) Abs to HIV. The Burton laboratory was joint first to isolate broadly neutralizing antibodies to HIV that demonstrate, in principle, the feasibility of an antibody-based HIV vaccine, and this study laid the groundwork for the rational development of vaccines against highly variable pathogens. Their prototype antibody (b12) was widely used to probe in vitro and in vivo activities of neutralizing antibody against HIV, including defining the CD4 binding site as a vaccine target, providing further understanding of the requirements for neutralization of HIV, and allowing the determination of the parameters of protective and therapeutic activities of bnAbs. In 2009, the lab discovered the first of the new generation of bnAbs, PG9/16, and subsequently described many more novel bnAbs — four of the five generally accepted HIV bnAb targets were first defined by Abs generated by the Burton lab.