# Generation of a polycistronic universal influenza virus vaccine based on rare species adenoviral vectors

> **NIH NIH R21** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $19,722

## Abstract

SUMMARY: Influenza A viruses (IAVs) cause serious respiratory illness in humans, with ~250,000-500,000
deaths per year globally. In addition to seasonal epidemics, the ongoing pandemic threat posed by new,
emerging, reassortant influenza viruses, for which humans are immunologically naive, represents a major
public health concern. Current influenza vaccines are impacted by several issues. These include, the elicitation
of narrow, strain-specific immune responses, an over-reliance on egg-based manufacturing methods, a
protracted production process (>6 months), the need to predict in advance which strains will circulate in
forthcoming seasons and the minimal induction of cellular and humoral immune responses to multiple influenza
antigens (Ags) simultaneously. The sub-optimal performance of seasonal influenza vaccines in recent years
has accelerated interest in developing a universal influenza virus vaccine, capable of providing broad and long-
lived protection against seasonal and pandemic subtypes. Strategies to achieve this include refocusing
immune responses towards highly conserved epitopes on influenza virus antigens such as the stalk of the
major surface glycoprotein, hemagglutinin (HA), the neuraminidase (NA) or the internal nucleoprotein (NP).
My research aims to develop an alternative, optimized, universal influenza vaccine platform which will
overcome issues associated with current vaccines using three approaches. (1) Firstly, I will optimize
polycistronic Ag expression cassettes, in which multiple IAV Ags are expressed simultaneously. These will
include bi- or tri-cistronic Ag cassettes featuring headless HAs from group 1 or group 2 IAVs in combination
with NA and/or NP. I will augment/broaden immune recognition of headless HA or NA by targeting Ags to host-
derived extracellular vesicles (EVs) including exosomes in vivo. This will be achieved by engineering fusion-Ag
constructs to tether Ag to a protein domain enriched in exosomes. Exosomes are nano-sized EVs which play
important roles in the regulation of immune responses, due to their ability to present Ag, in addition to MHC
and co-stimulatory molecules, to T- and B-cells. (2) Secondly, I will engineer these Ag constructs into non-
replicating, rare species adenoviral (Ad) vectored vaccines, which have established protocols for clinical
manufacturing, can be thermostabilized with minimal losses to immunogenicity under cold-chain free
conditions and have demonstrated safety and immunogenicity in infants, adults and the elderly in clinical trials.
(3) Finally, I will comprehensively evaluate and phenotype the magnitude and profile of these universal
influenza vaccines in single-shot regimens. These data will provide valuable information for the design of
subsequent prime:boost regimens and for challenge experiments in the future. In summary, the universal
influenza vaccine platform described in this proposal would be well-suited to stockpiling for pandemic
preparedness, and could prov...

## Key facts

- **NIH application ID:** 9989769
- **Project number:** 5R21AI146529-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Lynda Coughlan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $19,722
- **Award type:** 5
- **Project period:** 2019-08-16 → 2020-10-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989769

## Citation

> US National Institutes of Health, RePORTER application 9989769, Generation of a polycistronic universal influenza virus vaccine based on rare species adenoviral vectors (5R21AI146529-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9989769. Licensed CC0.

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