# Rapid response to pandemic influenza via multi-antigen RNA-based vaccine

> **NIH NIH R43** · TIBA BIOTECH, LLC · 2022 · $284,906

## Abstract

Project Summary
The proposal is to develop an RNA-based, rapid-response influenza vaccine prototype, supporting NIAID’s call
for nucleic acid-based vaccines that protect against pandemic influenza threats. Avian influenza A H7N9 causes
severe respiratory illness with a high mortality rate. The virus’ high zoonotic capacity has raised serious concerns
over the possibility of a pandemic, with the risk being potentially similar to that of H5 strains. While progress has
been made in the development of H5 influenza vaccines, H7 products have lagged. The proposed H7N9 vaccine
will be innovative in two respects. 1) H7N9 vaccines typically focus on the hemagglutinin (HA) protein as the
main immunogen, but immune responses to HA H7, while protective, are weaker than those against other HAs
in humans. Therefore, Tiba will develop a multi-antigen approach, specifically including optimized ratios of the
virion proteins HA, NA, M1, and NP. This approach is expected to increase the immunogenicity and heterotypic
protective potential of the vaccine. 2) Conventional lipid nanoparticles (LNPs), which are the mainstay of nucleic
acid delivery, require a large proportion of “structural” lipid, resulting in a relatively low RNA content. Tiba has
developed a modified dendrimer nanoparticle system that maximizes the delivered RNA mass content, protecting
RNA from degradation, and enables efficient uptake by cells in vivo. The prototype composition developed here
will serve as a platform into which any outbreak antigen sequences could be rapidly implemented. Tiba will meet
the near-term goal of developing a prototype HA/NA/M1/NP vaccine to advance toward live virus challenge
experiments and IND-enabling studies in Phase 2 by completing three Phase 1 Aims. The first is to validate
performance of a H7 HA replicon RNA-based expression construct in vivo. This will be generated and formulated
with Tiba’s delivery system and tested in BALB/c mice at 0.2 µg, 2.0 µg, and 20 µg to measure cellular and
humoral immunogenicity. These studies will establish the minimum dose required for subsequent experiments.
In the second Aim, Tiba will generate and test individual formulations of NA, M1, and NP mRNA and replicon
candidates, validating their performance in vivo at similarly increasing doses by T cell ELISpots and, for NA, also
by ELISA to measure antibody responses. The final Aim is to compose a multi-antigen prototype vaccine
combining the optimal balance of HA replicon RNA with NA, M1, and NP RNAs by co-encapsulating the four
payloads in a single nanoparticle formulation. This multi-antigen candidate vaccine will be tested in male and
female BALB/c mice, in comparison to HA-only and irrelevant antigen-coding control vaccines to determine if
immunogenicity is retained against all components, and if anti-HA responses benefit from inclusion of the
additional virion proteins. The candidate prototypes will be compared to state-of-the-art LNP formulations to
evaluate the performance ...

## Key facts

- **NIH application ID:** 10491533
- **Project number:** 1R43AI167158-01A1
- **Recipient organization:** TIBA BIOTECH, LLC
- **Principal Investigator:** Christian W. Mandl
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $284,906
- **Award type:** 1
- **Project period:** 2022-02-10 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10491533

## Citation

> US National Institutes of Health, RePORTER application 10491533, Rapid response to pandemic influenza via multi-antigen RNA-based vaccine (1R43AI167158-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10491533. Licensed CC0.

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