# Effects of obesity on the dynamics of Influenza transmission

> **NIH NIH R01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2022 · $811,115

## Abstract

OVERALL ABSTRACT
We, and others have shown that obesity is an independent risk factor for developing severe influenza infection.
However, the impact goes beyond disease severity. Viral clearance is impacted leading to prolonged viral
shedding. Vaccine efficacy is reduced and a recent study showed that overweight/obese adults shed
influenza virus 102% longer than average weight people. Using our newly developed diet-induced obese
(DIO) ferret model we now show that obesity impacts influenza transmission. An avian H9N2 virus that
does not transmit via airborne droplets in lean ferrets transmits in 100% of obese animals tested. These
findings have dramatic ramifications considering that the World Health Organization (WHO) predicts that most
of the world’s population lives in countries where being overweight and obese is more prevalent than being
underweight.
Our overall goal is to determine how obesity impacts influenza virus transmission. We will determine
whether enhanced transmission is due to changes in the virus, to increased susceptibility of the obese host, or
to a combination of both, answering questions on whether the virus evolves differently in the obese host as
compared to the lean host. Finally, we will explore whether vaccination protects lean and obese hosts. We
hypothesize that obese hosts, who have reduced immune function, may be acting as reservoirs for viruses,
allowing them to efficiently adapt to the new host and form genetic variants that can potentially be more easily
transmitted. Our proposed studies will fill a gap in knowledge by being the first work aimed at also
understanding host factors involved in transmission and the role of vaccination in stopping these events.
To accomplish our goal, we have proposed the following three interconnected but independent specific aims
that will address host-virus interactions:
1. Characterize virus diversity and quantify the dynamics of transmission.
2. Explore vaccine-based protection in the obese host and its effect on transmission.
3. Determine host susceptibility to influenza infection in the obese host.
We are uniquely suited to undertake this work given our combined expertise in influenza evolution and
transmission dynamics by deep sequencing, and impact of obesity on influenza disease severity and vaccine
responses. In addition to the obese ferret model, we have developed innovative tools to define the host
response in ferrets that will be invaluable to many investigators. Finally, we have access to longitudinal nasal
washes from influenza-infected human cohorts with corresponding body-mass index (BMI) data allowing us to
begin translating our findings to human health. In the long term, these studies may reveal critical new
information on the public health impact of obesity on influenza infection, transmission, and vaccine protection.
Information that is likely to extend beyond influenza.

## Key facts

- **NIH application ID:** 10401917
- **Project number:** 5R01AI140766-04
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** David Gresham
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $811,115
- **Award type:** 5
- **Project period:** 2019-06-10 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401917

## Citation

> US National Institutes of Health, RePORTER application 10401917, Effects of obesity on the dynamics of Influenza transmission (5R01AI140766-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10401917. Licensed CC0.

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