Project Grant R01AI201475

The National Institute of Allergy and Infectious Diseases awarded The Trustees of the University of Pennsylvania $3.16 million on September 1, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to investigate immune imprinting and cross-reactive antibody responses to pandemic influenza viruses.

The research examines how childhood exposure to seasonal influenza viruses creates long-lived immunological imprints that may provide protection against novel pandemic strains in adulthood. Preliminary findings show older individuals exposed to H1N1 or H2N2 viruses in childhood possess higher levels of antibodies cross-reactive to H5N1 compared to younger individuals exposed to H3N2, consistent with immune imprinting theory. The study will complete systematic serological evaluation of human antibody cross-reactivity against 18 hemagglutinin and 11 neuraminidase influenza virus subtypes, determine if different birth cohorts show increased susceptibility to distinct subtypes, and use a passive transfer humanized mouse model to investigate if cross-reactive antibodies contribute to protection. A second aim employs multiplexed single-cell transcriptomic techniques to identify human B cells producing neutralizing antibodies against hemagglutinin or neuraminidase proteins from diverse influenza viruses, develop monoclonal antibodies from these cells, and test their protective capacity in humanized mouse models against influenza infection.

The award supports work performed at the University of Pennsylvania in Philadelphia, Pennsylvania, from September 1, 2026, through August 31, 2030. This is a Project Grant, the standard NIH research award mechanism.