# RNA-based multi-antigen vaccine for SARS-CoV-2

> **NIH NIH R43** · TIBA BIOTECH, LLC · 2021 · $278,957

## Abstract

Project Summary/Abstract (30 lines)
The proposal is to develop an RNA-based multi-antigen SARS-CoV-2 vaccine, supporting NIAID’s call to develop
a vaccine using emerging antigen design strategies and novel delivery approaches. The SARS-CoV-2 pandemic
is actively threatening public health, world economies, and ways of life. Vaccine candidates are in human trials
now, but long-term solutions will require an adaptable vaccine system that can be universalized broadly to all
members of the coronavirus family. Tiba’s vaccine will be innovative in two respects: 1) The inclusion of all four
structural virion proteins will allow a deeper and potentially broader immune response against coronavirus, as
multiple conserved T cell epitopes will be presented by the vaccine. In addition, the incorporation of structural
proteins besides the Spike (S) protein will allow the formation of immunogenic VLPs in situ. 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 delivery molecule that
maximizes RNA mass content, protects RNA from degradation, and enables efficient uptake by cells. This
approach will increase immunogenicity and thus effectiveness of the vaccine. The first Phase 1 Aim is to optimize
candidate payloads comprising M, N, and E mRNA or saRNA. Conventional mRNAs encoding the M, N, and E
proteins will be codon-optimized and lead RNA payloads will then be formulated with Tiba’s modified dendrimer
delivery material. With the M, N, and E payloads generated in both saRNA and mRNA formats, effective
immunogenic doses for each will be determined by injecting six-week-old BALB/c mice with nanoparticles at
different doses. The antigen RNA payloads to proceed for titration into S RNA vaccine candidates will be
selected. The minimum effective dose for each M, N, and E mRNA or saRNA will be roughly estimated using a
regression model. Aim 2 will test the lead candidate payloads along with S in mice. Combination formulations
will be generated wherein different masses of the lead M, N, and E RNAs are titrated into the optimal S mRNA
or saRNA formula to identify a formulation mixture that maximizes M, N, and E cellular immune responses while
not suppressing the S humoral response. Treatment doses will deliver the same mass of S RNA across all
groups, and that optimal mass will be chosen based on the results of dose-finding preliminary studies. Using the
results of the study, two mixtures that confer detectable responses against each virion component while not
suppressing S antibody and T cell responses will be selected as lead candidates. For Aim 3, the lead candidates
will be used in a hamster challenge study. Vaccinations will be performed by i.m. injection in golden Syrian
hamsters. Challenges will be performed using the current best practice. The benchmark of success for this study
is evidence ...

## Key facts

- **NIH application ID:** 10259605
- **Project number:** 1R43AI162469-01
- **Recipient organization:** TIBA BIOTECH, LLC
- **Principal Investigator:** Christian W. Mandl
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $278,957
- **Award type:** 1
- **Project period:** 2021-05-01 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10259605

## Citation

> US National Institutes of Health, RePORTER application 10259605, RNA-based multi-antigen vaccine for SARS-CoV-2 (1R43AI162469-01). Retrieved via AI Analytics 2026-06-03 from https://api.ai-analytics.org/grant/nih/10259605. Licensed CC0.

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