Professor / The Scripps Research Institute
The Scripps Research Institute 10550 N Torrey Pines Road, IMM28, La Jolla, CA 92037
In his research, Dr. Wyatt and his team are focused on the HIV-1 envelope glycoprotein (Env) structure and function to define B cell and antibody responses that are elicited following Env vaccination.
Over the past 25 years, Dr. Wyatt and his team have used structural and biophysical characterization of Env to improve elicitation of neutralizing antibodies following Env trimer in animal models.
The Wyatt lab is a leader in developing native-like, cleavage-independent trimers that are faithful mimics of the functional spike. They use state-of-the-art biophysical techniques such as size-exclusion chromatography, BLI, differential scanning calorimetry and EM to characterize these trimers and antibodies elicited by these trimers following vaccination in non-human primates and other relevant animal models.
The highly collaborative atmosphere at the Scripps Research Institute at the IAVI Center for Neutralizing Antibodies creates an ideal environment to study Env-based trimers and immunogenicity. Over the past several years, Dr. Wyatt and his team have developed numerous tools to map polyclonal antibody responses to Env, serum HIV neutralizing capacity and to isolate B cells from HIV-1 Env trimer-immunized small animals (mice, guinea pigs and rabbits) and non-human primates to determine BCR/mAb binding affinities, neutralizing capacity and epitope specificities.
They explore the effects of Env trimer particulate display when arrayed at high-density on synthetic liposomes and other virus-like platforms and investigate the capacity of targeted N-glycan deletion to enhance the quantity of B cell and antibody responses to well-ordered, stabilized HIV-1 Env trimers. Their vision is to combine structure-based Env immunization, iterative design and multi-valent display to present Env to the immune system in ways not encountered (and escaped from) during natural infection.
As a part of this rationale, they propose to target natural gaps in the highly effective Env N-glycan shield. In this epitope-based approach, Wyatt lab plans to exploit the full capacity of the B cell repertoire and immune system to more efficiently isolate HIV-1 cross-neutralizing antibodies towards a broadly effective vaccine.