Project Grant R01AI201398

The National Institute of Allergy and Infectious Diseases awarded Scripps Research Institute $919,363 on August 17, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to investigate the molecular mechanisms governing plasma cell longevity and the establishment of long-lived plasma cells (LLPCs) at mucosal surfaces and bone marrow.

The research addresses why current influenza vaccines require annual boosters by examining how plasma cells generated during viral infection or vaccination—specifically from influenza, rotavirus, and norovirus—evolve over time and achieve long-term persistence. The project employs an innovative transgenic mouse model enabling real-time tracking of germinal center-derived plasma cells to reveal which distinct cohorts survive, where they reside, and which successfully establish long-term persistence. This model will be combined with high-throughput technologies including single-cell RNA sequencing and B-cell receptor sequencing to define the molecular basis for whether mucosal plasma cells join the LLPC pool or undergo cell death. The work addresses a fundamental gap: while it is known that LLPCs originate from germinal center direct export or germinal center-derived memory B cells, the mechanisms determining their longevity and promotion of both IgG and IgA isotypes at mucosal surfaces remain poorly understood.

Performance occurs in La Jolla, California, with a period of performance through July 31, 2031.