Tolia Research Group

The Host-Pathogen Interactions and Structural Vaccinology Section (HPISV) seeks to uncover the fundamental phenomena necessary to develop the next generation of vaccines through structural vaccinology. Structure-guided design of immunogens to elicit well-defined immune responses will likely lead to significant improvements in vaccine efficacy and durability.

We pursue three areas of research:

1. Host-pathogen interactions
   Pathogens must interact with the host for survival. We aim to uncover and exploit these interactions to prevent disease.
2. Neutralizing Antibodies
   Antibodies play key roles in protection against infectious disease. We aim to determine the mechanisms of productive antibody neutralization of pathogens.
3. Structural vaccinology for infectious diseases
   Producing antigens that focus the immune response to protective epitopes and result in durable protection is critical for future vaccines. We aim to design and engineer novel antigens with enhanced efficacy and durability.

We focus on the infectious diseases malaria and COVID-19. Malaria affects a third of the world`s population, leads to 200-300 million cases per year, and results in approximately half a million deaths annually. A majority of fatalities are suffered by children under the age of five. Most morbidity and mortality due to malaria are caused by the parasites Plasmodium falciparum and Plasmodium vivax. Vaccines against these pathogens are likely to play key roles in malaria control efforts and are expected to be a central component for the eradication of malaria through an integrated program. COVID-19 has emerged as a significant global health priority and continuous development of vaccines is necessary to ensure protection against new variants. We aim to leverage structural vaccinology to develop potent and durable vaccines for malaria and COVID-19.

HPISV uses the tools of structural biology, biochemistry, biophysics, immunology, and microbiology to examine proteins and protein complexes associated with pathogenesis. Specific approaches include:

• X-ray crystallography, Electron microscopy, Biophysical methods (SAXS, BLI, ITC, AUC)
• Human monoclonal antibody isolation, characterization, and examination
• Human-guided and computational protein design
• In vitro functional assays and in vivo preclinical studies in rodents and non-human primates