# Programming Durable Immune Responses To Vaccination > **NIH NIH U01** · WASHINGTON UNIVERSITY · 2024 · $593,729 ## Abstract ABSTRACT mRNA-based vaccines use lipid nanoparticles to transport mRNA-encoding antigens to the host cells. We have recently shown that SARS-CoV-2 mRNA vaccination in humans induces a robust plasmablast response in blood and a persistent GC reaction in the draining lymph nodes. This corresponded with enhanced anti-spike antibody avidity in blood and enhanced affinity and neutralization capacity of bone marrow plasma cell (BMPC)-derived monoclonal antibodies (mAbs). mRNA-based influenza vaccines could be a promising alternative to conventional influenza vaccine platforms because of their high immunogenicity. The following questions, however, are yet to be addressed: (1) does an mRNA-based influenza vaccination induce a robust and persistent GC reaction in humans? (2) if yes, what drives such persistence, and how different is that from the GC response induced by conventional influenza vaccines? (3) can an mRNA-based influenza vaccination induce a robust GC response in the elderly (>65 years old)? (4) does robust GC response to influenza vaccination in humans correlate with a more durable antibody response? (5) does an mRNA-based influenza vaccination induce a more sustained increase in the frequency of long-lived BMPCs compared to conventional vaccines? (6) can a vaccine-induced robust GC response overcome influenza antigenic imprinting in humans? (7) what are the molecular determinants that dictate the persistence of BMPCs? Addressing these questions will allow us to discern the cellular and molecular determinants associated with durable antibody responses to vaccination in humans. We will directly examine antigen-specific GC and long-lived BMPC responses induced after mRNA-based and conventional influenza vaccination in humans in the proposed studies. These responses will be examined in 18- 50 year-old and 65-80 year-old human adults. We will assess the persistence of the vaccine antigen in draining lymph nodes as a potential mechanism for driving GC longevity in humans. We will examine how robust GC B cell responses to influenza vaccination in humans could overcome antigenic imprinting and if that correlates with a more durable antibody response. Finally, we will genetically analyze the mechanisms of action of the transcriptional determinants that are preferentially expressed in plasma cells destined for longevity. Our findings will potentially reveal the cellular and molecular determinants dictating the longevity and the breadth of elicited antibody responses to influenza – and potentially other – vaccination in humans. ## Key facts - **NIH application ID:** 10763701 - **Project number:** 2U01AI141990-06 - **Recipient organization:** WASHINGTON UNIVERSITY - **Principal Investigator:** Ali Hassan Ellebedy - **Activity code:** U01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $593,729 - **Award type:** 2 - **Project period:** 2018-12-18 → 2028-12-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10763701 ## Citation > US National Institutes of Health, RePORTER application 10763701, Programming Durable Immune Responses To Vaccination (2U01AI141990-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10763701. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*