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

> **NIH NIH P01** · BOSTON CHILDREN'S HOSPITAL · 2021 · $2,701,758

## Abstract

Abstract
An essential objective for vaccines to protect against viruses that continually evolve to escape
host immunity -- influenza and HIV being the most prominent human pathogens of current
interest in this regard -- is to target selected, conserved epitopes and to understand and
anticipate viral escape mechanisms. An underlying premise of this Program Project grant is that
analysis of B-cell ontogeny following influenza-virus vaccination or infection can facilitate design
of immunogens to elicit a "broadly neutralizing" response. We seek to answer critical questions
about immune-response mechanisms, immunization strategies and B-cell immunogen design in
quantitative terms and hence to provide a more secure structural and biophysical foundation for
vaccine development. The proposed research strategy focuses on antibodies that recognize the
receptor-binding site (RBS) on influenza HA -- one of two conserved sites shown to be broadly
neutralizing antibody (bnAb) targets. We will combine analysis of human repertoires in response
to influenza vaccination with similar analyses of repertoires following experimental
immunizations of mice and rhesus macaques. We will test hypotheses concerning imprinting of
the immune response by initial infection or vaccination, establish how reinfection or
revaccination with HA presenting a mutated epitope influences broadening of the response
through further affinity maturation, and integrate what we learn into tests in of proposals for
immunogen design

## Key facts

- **NIH application ID:** 10229498
- **Project number:** 5P01AI089618-10
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** STEPHEN COPLAN HARRISON
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,701,758
- **Award type:** 5
- **Project period:** 2011-08-01 → 2023-04-06

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10229498

## Citation

> US National Institutes of Health, RePORTER application 10229498, Structure-function analysis of infection- and vaccine-induced B-cell repertoires (5P01AI089618-10). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10229498. Licensed CC0.

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