Scripps Research Institute has received a USD 3.68 million NIAID R01 grant to develop a multicomponent self-assembling protein nanoparticle platform targeting three influenza antigens simultaneously, with the goal of producing a vaccine effective against both seasonal and pandemic strains.
The award, running through July 2030, funds co-principal investigators Ian A. Wilson and Jiang Zhu at the La Jolla, California nonprofit. The grant aligns with the National Institute of Allergy and Infectious Diseases (NIAID) Strategic Plan for universal influenza vaccine development.
Current seasonal influenza vaccines offer 10–60% effectiveness, largely because they require annual reformulation to match circulating strains. The platform being developed at Scripps Research integrates stabilized hemagglutinin (HA) trimers, neuraminidase (NA) monomers, and the conserved extracellular domain of matrix protein 2 (M2e) onto single-component self-assembling protein nanoparticles (SApNPs). The rationale is that combining neutralizing antibody responses to HA, NA-inhibitory antibodies, and Fc-mediated effector functions targeting M2e may provide broader, more durable protection than single-antigen approaches.
A central element of the work involves novel HA stabilization mutations — specifically N95L in influenza A viruses (IAVs) and Q442L in influenza B viruses (IBVs) — designed to lock HA trimers in a prefusion-like conformation. Preliminary data cited in the grant indicate that constructs bearing these mutations produced robust neutralizing antibody titers and conferred protection in animal models. The team will also explore a glycoengineering strategy incorporating core α(1,3)-fucose residues into HA and NA glycans to enhance immune recognition, alongside kifunensine-mediated oligomannose enrichment, which the investigators report previously improved HA-induced neutralizing antibody responses.