# Safety and Immunogenicity of novel, live-attenuated V4020 vaccine for Venezuelan Equine Encephalitis (VEE) in healthy adults

> **NIH NIH U01** · MEDIGEN, INC. · 2024 · $562,567

## Abstract

ABSTRACT
 Venezuelan Equine Encephalitis virus (VEEV) is a life-threatening, NIH/NIAID category B human pathogen
and a potential bioterrorism threat. Outbreaks of VEEV occur in Central America and have previously spread
into the United States. The potentially devastating effects of VEEV reemergence in the U.S. demand an
effective vaccine to protect immunologically naïve population. Currently, live attenuated TC-83 vaccine is used
under IND protocol for vaccination of medical personnel at risk. The vaccine causes adverse effects, and
efforts to develop an improved VEEV vaccine are underway. However, because vaccine development is a
lengthy process and the supply of TC-83 vaccine is limited, the U.S. may soon experience a shortage of the
VEEV vaccine. This can leave the U.S. population and at-risk personnel unprotected. Furthermore, in the
absence of a vaccine, VEEV may fit the CDC definition of a BSL4 Select Agent.
 During previous NIH-supported research, Medigen evaluated a new platform technology for the
development of vaccines against VEEV and, potentially, other viral diseases. The proposed V4020 vaccine
includes attenuating rearrangement of the capsid and glycoprotein genes within the full-length genomic RNA.
The attenuating rearrangement effectively prevents reversion because many independent mutations would be
needed to revert to the pathogenic genotype. In addition, vaccine is made from a DNA copy of the rearranged
RNA genome placed in the iDNA® infectious clone downstream from the CMV promoter. The key feature of
iDNA infectious clone (and the difference from standard cDNA clone) is that live attenuated virus is launched
from the plasmid, without the need for in vitro transcription. The use of genetically stable iDNA improves
vaccine safety. In preliminary research, the V4020 virus containing rearranged genomic RNA and prepared
from iDNA clone showed safety advantages and protection against VEEV challenges in BALB/c mice and in a
cynomolgus macaque non-human primate (NHP) model.
 Specific Aim 1. Safety of V4020 live-attenuated VEEV vaccine in human subjects. Medigen in collaboration
with U.S. Army Medical Research Institute for Infectious diseases (USAMRIID), to conduct Phase 1a, first-in-
human study evaluating safety of V4020 VEEV vaccine in healthy adults. We propose a double blinded,
placebo controlled, single-dose escalation study in 39 healthy adults, 18-50 years of age. Medigen will
manufacture cGMP lot of V4020 vaccine and communicate with the FDA regarding clinical trial design. Groups
of volunteers (13 subjects/group) will receive a single 104, 105, or 106 PFU dose of V4020 vaccine (10/group),
with 3 subjects from each group randomized to receive placebo. The low dose will be administered first, and
there will be at least 14 days delay before another group will start receiving the higher dose of vaccine. The
study is designed to assess the safety of V4020 vaccine administered by subcutaneous (SC) administration.
 Specific Aim 2....

## Key facts

- **NIH application ID:** 10815801
- **Project number:** 5U01AI155406-03
- **Recipient organization:** MEDIGEN, INC.
- **Principal Investigator:** Peter M. Pushko
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $562,567
- **Award type:** 5
- **Project period:** 2022-03-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10815801

## Citation

> US National Institutes of Health, RePORTER application 10815801, Safety and Immunogenicity of novel, live-attenuated V4020 vaccine for Venezuelan Equine Encephalitis (VEE) in healthy adults (5U01AI155406-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10815801. Licensed CC0.

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