# Toward a universal influenza virus vaccine based on live attenuated NS1-deleted influenza viruses

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $1,262,646

## Abstract

Influenza viruses continue to pose a significant threat to global public health. Consequently, there is a vitally
important need to generate new influenza virus vaccines and innovative vaccination strategies. The
development of a long-lived broadly-protective influenza virus vaccine would have a tremendous impact on
worldwide efforts to control influenza viruses. The purpose of this application is to accelerate the development
of a universal influenza virus vaccine through the preclinical development of two lead candidate components of
such a vaccine. Since our initial discovery that sequential immunization with influenza vaccines based on
chimeric HAs induce broad protection against diverse influenza virus strains in animal models, we have
moved into Phase 1 clinical trials that investigate the safety and immunogenicity of inactivated
adjuvanted and cold-adapted live attenuated influenza A virus vaccines containing chimeric group 1
influenza virus HAs. Such vaccines induce protective immunity in mice, ferrets and pigs against all group 1
influenza A virus, including H1, H2 and H5 viruses. Protection correlates with the induction of high levels of
cross-reactive Fc-receptor engaging antibodies against the conserved group 1 HA stalk. If any of these
vaccination strategies are successful in humans, addition of group 2 influenza A and influenza B chimeric HAs
would result in protection against any type, subtype and strain of influenza virus. This “universal flu vaccine”
would eliminate the need for annual influenza virus vaccination and prevent future influenza pandemics. In the
current application we propose to generate GMP clinical lots and IND-enabling information to subsequently
perform human clinical trials with a highly immunogenic vaccine platform expressing chimeric HAs based on
live attenuated delNS1 influenza viruses. In contrast to the cold-adapted influenza vaccines, delNS1 influenza
vaccines are highly immunostimulatory due to the removal of the immune antagonist gene NS1. For the
purpose of this grant, our group at Icahn School of Medicine at Mount Sinai, which pioneered the use of
chimeric HAs for universal influenza virus vaccination, has partnered with Vivaldi, a biotechnology company
that has delNS1-based influenza virus vaccines under clinical development. At the end of our proposal, we
will have generated two GMP lots of delNS1-based group 1 chimeric HA influenza virus vaccines ready
for clinical investigation. These lots will be used after completion of our grant for sequential immunizations in
humans to obtain their safety and immunogenicity profiles. Moreover, we anticipate that human influenza virus
challenge studies after vaccination with inactivated, cold-adapted and delNS1-based chimeric HA vaccines will
differentiate the vaccine platform among these three resulting in best levels of protection. The best platform will
be used as the basis for further clinical development and incorporation of group 1, group 2 and influenza ...

## Key facts

- **NIH application ID:** 9846199
- **Project number:** 5R01AI141226-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Adolfo Garcia-Sastre
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,262,646
- **Award type:** 5
- **Project period:** 2019-01-07 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9846199

## Citation

> US National Institutes of Health, RePORTER application 9846199, Toward a universal influenza virus vaccine based on live attenuated NS1-deleted influenza viruses (5R01AI141226-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9846199. Licensed CC0.

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