Iterative immunogen optimization to focus immune responses on a conserved, subdominant viral epitope.

ABSTRACT: Designing effective vaccination strategies against genetically diverse viruses, such as HIV or influenza, is hindered by the ability of these pathogens to mutate and readily evade immune control. While these viruses contain conserved regions that cannot easily mutate without affecting viral fitness, these sites are subdominant, meaning that they are not the primary target of immune responses elicited by natural infection or current vaccines. Here, we integrated recent advances in machine learning methods for protein structure prediction and design to engineer protein immunogens that focus immune responses on a conserved, subdominant HA epitope targeted by broadly cross-reactive influenza antibodies. Iterating between computation-guided optimization and in vivo analyses generated imm

SUBMITTER: Marston DJ 

PROVIDER: S-EPMC12637436 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature