# Structure-function analysis of infection- and vaccine-induced B-cell repertoires

> **NIH NIH P01** · BOSTON CHILDREN'S HOSPITAL · 2024 · $2,972,315

## Abstract

Abstract - Overall
Influenza virus evolves in response to pressure from herd immunity, resulting in progressive variation
of viral antigenicity and limiting vaccine efficacy. The goal of this Program project is to establish a
secure mechanistic foundation for novel vaccination strategies that might confer long-lasting immunity
in face of rapid antigenic variation of currently circulating subtypes and in anticipation of potential
introduction of zoonotic subtypes into the human population. The breadth of expertise in our four
collaborative Projects and three scientific Cores and Results from the current and previous grant
cycles allow us to pursue the following Specific Aims. (1) Can a suitable vaccination strategy modify
or redirect immune "imprinting" -- the observed influence of an individual's history of infection of
vaccination on their response to an antigenically drifted strain or novel subtype? We will determine
the full scope of the human humoral response to vaccination in individuals of all ages (infants to
seniors) and hence of varying exposures, and we will carry out, in non-human primates (NHPs),
experiments to compare imprinting by infection and vaccination. (2) We have found (in mice) a strong
effect of the anatomical location of immunization with protein antigen on the response to a subsequent
immunization. We will determine whether this effect extends to infection and whether it is also true in
NHPs. Experiments in mice will determine whether components of TFH cell memory are similarly
localized and test the contribution of conserved T-cell epitopes to humoral imprinting. (3) We will
design novel vaccine antigens to extend previous studies of human immune responses (focused on
hemagglutinin) to influenza neuraminidase (NA) and to determine the importance of T-cell epitope
diversity for design of optimized immunogens. We will also create a model for co-evolution of virus
(immune escape) and humoral immunity (antibody affinity maturation) using directed molecular
evolution in the laboratory.

## Key facts

- **NIH application ID:** 10824215
- **Project number:** 5P01AI089618-12
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** STEPHEN COPLAN HARRISON
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,972,315
- **Award type:** 5
- **Project period:** 2011-08-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10824215

## Citation

> US National Institutes of Health, RePORTER application 10824215, Structure-function analysis of infection- and vaccine-induced B-cell repertoires (5P01AI089618-12). Retrieved via AI Analytics 2026-06-24 from https://api.ai-analytics.org/grant/nih/10824215. Licensed CC0.

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