Signature Seminar Series: Immunogen Design to Target Conserved Regions of Rapidly Evolving Pathogens

ABOUT THE LECTURE:
Rapidly evolving pathogens like HIV, influenza, and SARS-CoV-2 escape immune responses by accumulating mutations in their surface proteins without losing fitness. However, viral surface proteins also contain highly conserved regions that are essential for receptor binding and fusion with target cells. Antibodies against some of these conserved sites have been isolated and show broad recognition of diverse viral variants, but they are typically poorly elicited by natural infection or current vaccines. In this seminar, I will describe general vaccine design strategies that employ machine learning based protein structure design and prediction to elicit antibodies against conserved epitopes on HIV and coronaviruses, such as epitope grafting, germline targeting, epitope masking, or nanoparticle design. Engineered immunogens have been shown to elicit target antibodies in relevant animal models, demonstrating the utility of our approaches and their potential to contribute to the development of broadly protective vaccines.