# Development of reassortment-deficient influenza vaccine candidates: Rewiring packaging signals

> **NIH NIH F30** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $45,360

## Abstract

Project Summary
Influenza is a major cause of morbidity and mortality worldwide, with seasonal epidemics causing an estimated
290,000 to 650,000 deaths every year. Annual vaccine efficacy can be as low as 10% due to antigenic
mismatch between circulating influenza strains and vaccine strains, underscoring the need for a universal
influenza virus vaccine. Our lab has developed a novel vaccination strategy utilizing chimeric hemagglutinin
(HA) constructs to shift the host immune response from the antigenically variable HA head domain to the
conserved HA stalk. Vaccination with live attenuated influenza virus vaccines (LAIVs) expressing these
constructs elicits broad protection against different influenza virus strains in animal models. However, concern
regarding the reassortment potential of LAIVs with wild-type circulating viruses impedes consideration of wide-
scale vaccination with LAIVs containing novel HAs and confines clinical trials with these vaccines to
containment units. Previous work from our lab has provided evidence that packaging signals located at the 3'
and 5' termini of the viral genomic RNA segments can be utilized to control influenza virus reassortment. By
swapping the packaging signals of two segments, we prevented free reassortment of those segments. Based
on these data, I have generated more viruses with additional rewired packaging signals to define their
reassortment potential using coinfection studies under the hypothesis that they will be reassortment-deficient.
To better understand the mechanistic underpinnings of selective packaging, I will perform transposon
mutagenesis on the HA vRNA segment and map the specific sequences implicated in key RNA-RNA
packaging interactions. The ultimate goal of this project is to establish a novel platform for the development of
LAIVs that are unable to freely reassort and gain an understanding of the nucleotide interactions at play in
influenza genome packaging and reassortment. This would allow us to create LAIV candidates that contain
HAs novel to the human population for either universal or prepandemic vaccination purposes.

## Key facts

- **NIH application ID:** 10074129
- **Project number:** 5F30AI143243-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Allen Zheng
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,360
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10074129

## Citation

> US National Institutes of Health, RePORTER application 10074129, Development of reassortment-deficient influenza vaccine candidates: Rewiring packaging signals (5F30AI143243-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10074129. Licensed CC0.

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