# Modeling Mechanisms of Adjuvanted Influenza Vaccine Induced IgG Repertoire Diversity and Heterosubtypic Immunity

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2020 · $687,168

## Abstract

Annual immunization against influenza infection is one of the largest coordinated international public health
efforts. Current flu vaccination strategies primarily elicit protection by the generating long lasting type-specific
neutralizing IgG anti-hemagglutinin (HA) antibodies that bind to molecularly similar influenza subtypes. This
phenomenon is termed antibody mediated heterosubtypic immunity (amHSI), and a major reason for the
success of seasonal influenza vaccination. MF59 is a squaline-oil adjuvant recently approved for seasonal
influenza vaccination in indivduals ≥65 years of age. Our preliminary data suggests that MF59 increases
amHSI in mice, ferrets and human subjects. Thus the primary goal of this Project is to elucidate and model the
mechanisms of by which MF59 adjuvanted seasonal influenza vaccine increase B cell mediated amHSI at the
immunoglobulin heavy chain DNA and protein repertoire level. Aim 1: To test the hypothesis that MF59
adjuvant increases the breadth, depth and molecular sequence diversity in the IgG repertoire after influenza
vaccination. Aim 2: To build and validate an age-dependent branching process model of heterosubtypic
immunity coverage induced by adjuvanted influenza vaccine. Aim 3: To model and identify the mechanisms
responsible for MF59 adjuvanted influenza vaccine induced anti-HA IgG repertoire evolution and amHSI
generation in human vaccine recipients. This proposal addresses a highly significant issue in public health, how
to optimize the protection of the influenza vaccine using vaccine adjuvants to increase the cross-strain reactivity
of the resulting mixture of IgG anti-HA antibodies. It also addresses a significant gap in scientific methods for
reconstructing Ig sequence lineages resulting from hyperaccellerated somatic mutation within germinal center
reactions. We will create age dependent branching process models that will provide mechanistic insight into
how the adjuvant and intradermal vaccination alter the molecular diversity of antibody-mediated HSI. These
models will be first developed using mice vaccinated with MF59 adjuvanted influenza vaccine in Aim 1, and
then extended to human subjects in Aim 2. If successful, this work will provide a general framework for
modeling the molecular processes involved in the generation of amHSI.

## Key facts

- **NIH application ID:** 9851740
- **Project number:** 5R01AI129518-04
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Ollivier Hyrien
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $687,168
- **Award type:** 5
- **Project period:** 2017-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851740

## Citation

> US National Institutes of Health, RePORTER application 9851740, Modeling Mechanisms of Adjuvanted Influenza Vaccine Induced IgG Repertoire Diversity and Heterosubtypic Immunity (5R01AI129518-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9851740. Licensed CC0.

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