# Circularization of RNA to improve the durability of the vaccine immune response

> **NIH AI R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2026 · $798,400

## Abstract

ABSTRACT
 mRNA vaccines are one of the most promising vaccine platforms available to rapidly deploy in response
to emerging viral infections. However, the duration of the protective antibody response induced by these vaccines
is limited, even after multiple vaccine doses. The rapid decay of the antibody response to mRNA vaccines
necessitates frequent revaccinations.
 The immunogenicity of vaccines based on conventional mRNA may be reduced due to triggering TLR 3,
7 and 8, and RIG-I receptors resulting in strong induction of the innate immune response. This leads to
expression and activation of protein kinase R and 2’-5’-oligoadenylate synthetase, which in turn leads to
suppression of translation. As circular RNA does not have termini, it stimulates innate immune responses
weaker. Moreover, circular RNA has the advantage of prolonged expression due to resistance to exonucleases.
A protein produced from circular RNA is detectable in serum or at a site of injection for a much longer period of
time as compared to linear mRNA. Extended antigen availability to mimic the natural kinetics of antigen delivery
during viral infections has shown to be highly effective in potentiating germinal center responses to immunogens.
 Hantaviruses are globally emerging pathogens; the New World hantaviruses Andes virus (ANDV) and
Sin Nombre virus cause hantavirus cardiopulmonary syndrome with a case fatality rate up to 40%. A recent
outbreak of ANDV demonstrated transmission through direct contact with infected individuals but also airborne
human-to-human, highlighting the significant pandemic potential of this virus.
 The proposal is based on extensive preliminary data which show that ANDV linear mRNA vaccine
platforms are protective against ANDV challenge in the 100% lethal hamster model. The proposal is aimed at
testing the hypothesis that the innovative circular RNA vaccine construct against ANDV will elicit the most potent
adaptive immune response including diversity and magnitude of

## Key facts

- **NIH application ID:** 11330568
- **Project number:** 5R01AI184768-02
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Robert Koehler Abbott; Alexander  Bukreyev
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** AI
- **Fiscal year:** 2026
- **Award amount:** $798,400
- **Award type:** 5
- **Project period:** 2025-05-05T00:00:00 → 2030-04-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11330568

## Citation

> US National Institutes of Health, RePORTER application 11330568, Circularization of RNA to improve the durability of the vaccine immune response (5R01AI184768-02). Retrieved via AI Analytics 2026-06-26 from https://api.ai-analytics.org/grant/nih/11330568. Licensed CC0.

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