# Novel Chikungunya vaccine with rearranged genome

> **NIH NIH R43** · MEDIGEN, INC. · 2021 · $120,042

## Abstract

ABSTRACT
 Chikungunya fever virus (CHIKV) is a mosquito-borne alphavirus that causes wide-spread human
infections and epidemics in Asia, Africa and recently, in the Americas. There is an increased risk of CHIKV
pandemic due to climate and ecological change and international travel. Currently, there is no approved
vaccine. Previous experimental approaches include the US Army-developed IND vaccine, 181/25, that
contains two attenuating mutations in the E2 protein. The 181/25 vaccine showed high immunogenicity in
Phase II clinical trial; however, adverse reactions justify the need for safety improvement. Medigen has
developed a DNA-launched, live-attenuated vaccine, termed iDNA®, in which the full-length genome of the
181/25 IND vaccine virus is transcribed from a CMV promoter on a plasmid. Injection of the plasmid
intramuscularly launches the live-attenuated vaccine virus. This approach has the advantages of DNA
vaccines, including the encoding of the vaccine virus by a genetically stable DNA plasmid, and the high efficacy
of live-attenuated vaccines.
 To address the need for improved safety of the 181/25 vaccine, we propose a genomic rearrangement as
an additional attenuating mutation. This genomic rearrangement (RA181/25) does not change immunogenic
epitopes but is resistant to reversion since multiple, independent mutations would be needed for reversion. In
Specific Aim 1, we prepare the rearranged (RA181/25) CHIKV iDNA vaccine and evaluate it in vitro for plaque
phenotype, growth curve, and genetic stability by next generation sequencing (NGS), as compared to non-
rearranged iDNA and the 181/25 IND vaccine virus. In Specific Aim 2, RA181/25 CHIKV iDNA is evaluated in
two mouse models (inbred C57BL/6 and outbred CD-1) as compared to the non-rearranged CHIKV iDNA
and the 181/25 IND vaccine virus. We propose to use electroporation, microneedles, and liposomal
formulations to optimize the iDNA vaccination, and we will evaluate safety, immunogenicity (neutralizing
antibody and cell-mediated responses), and protective efficacy against CHIKV challenge in both animal
models. The successful proof-of-concept demonstration of a safety advantage of the RA181/25 CHIKV iDNA
vaccine would advance a novel single-dose vaccine with many advantages for protecting populations at risk
for CHIKV infection, as well as for rapidly controlling CHIKV outbreaks.

## Key facts

- **NIH application ID:** 10137889
- **Project number:** 5R43AI152717-02
- **Recipient organization:** MEDIGEN, INC.
- **Principal Investigator:** Peter M. Pushko
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $120,042
- **Award type:** 5
- **Project period:** 2020-04-03 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10137889

## Citation

> US National Institutes of Health, RePORTER application 10137889, Novel Chikungunya vaccine with rearranged genome (5R43AI152717-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10137889. Licensed CC0.

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