# Evolution and Transmission of Influenza Virus in Natural Human Infection

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $746,786

## Abstract

Seasonal influenza epidemics result in significant morbidity and mortality, and vaccine effectiveness is
disappointingly low. The rapid evolution of influenza viruses is a major barrier to effective vaccines, as new
strains with different antigenic properties are continuously generated within a remarkably large population of
infected hosts. This problem was highlighted in the recent NIAID strategic plan for influenza and in PA-18-859,
which highlight key knowledge gaps with respect to influenza virus evolution in individuals and its transmission
between them. The long-term goal of this research is to elucidate the evolutionary and epidemiological dynamics
of influenza viruses in naturally infected human hosts. The objectives of this project are to use state-of-the-art
molecular approaches to define the host-level evolution of influenza and to identify correlates of infectivity and
transmission. This project will combine intensive sampling of viruses, matched sera, and clinical data from
naturally infected individuals and their contacts, which will allow for robust analyses of influenza evolution,
transmission, and spread. The feasibility of this approach is supported by published preliminary data, which show
that (i) serial sampling can be used to characterize the evolutionary dynamics of influenza viruses within naturally
infected people; (ii) next generation sequencing (NGS) can be used to identify transmission pairs and to estimate
the number of unique viral variants transmitted between individuals; (iii) temporal data on viral load and within-
host genetic diversity can inform mathematical models of transmission. Detailed analyses of influenza evolution
and transmission will be accomplished in three aims. (Aim 1) Identify the emergent antigenic variants that are
positively selected with hosts. NGS of serially sampled within-host viral populations will be used to identify
hemagglutinin and neuraminidase variants under positive selection within hosts and their relationship to host
immune status. The impact of these mutations on viral antigenicity will be evaluated using sera from enrolled
individuals. (Aim 2) Define the transmission bottleneck and the genetic variants that are transmitted. NGS of
serial samples from index cases and household contacts will be used to define household transmission chains,
the size of the transmission bottleneck, and which within host variants are transmitted. (Aim 3) Identify viral and
host factors associated with host susceptibility, infectivity, and transmission. A strain-specific household
transmission model, integrating molecular and epidemiologic data, will be used to estimate hazards of infection
from the community and each infected household contact. This work is innovative, because it leverages the
expertise of an existing productive team to combine state-of-the-art technologies for viral sequencing and
sophisticated modeling approaches to study influenza virus evolution and transmission in natural infect...

## Key facts

- **NIH application ID:** 10450656
- **Project number:** 5R01AI148371-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Adam Lauring
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $746,786
- **Award type:** 5
- **Project period:** 2020-07-02 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10450656

## Citation

> US National Institutes of Health, RePORTER application 10450656, Evolution and Transmission of Influenza Virus in Natural Human Infection (5R01AI148371-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10450656. Licensed CC0.

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