# Mosaic Immunogens as Multivalent Alphavirus Vaccines

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2020 · $474,362

## Abstract

Abstract
 Recent epidemics of chikungunya virus (CHIKV), Ebola virus or Zika virus have shown how viruses
previously considered a low threat can emerge suddenly, destroying lives and economies. Multivalent
treatments or vaccines that are effective against diverse virus strains are needed to deal with emerging threats
before they reach epidemic status. In this proof of concept project, we will use a protein structure- and epitope-
based approach to construct a multivalent vaccine against two quite diverse mosquito borne alphaviruses, both
severely effecting human health and with periodic outbreaks in the Americas, including the US, Venezuelan
equine encephalitis virus (VEEV), which has a high mortality in zoonotic outbreaks in humans, and CHIKV,
which can cause chronic arthralgia. We hypothesize that an optimized attenuated virus, expressing
mosaic envelope proteins projecting epitopes from both CHIKV and VEEV, will induce protective
antibodies against both parent viruses as well as a wide spectrum of alphaviruses. A vaccine
incorporating this would substantially reduce the cost and regulatory burden compared to the current “cocktail”
approach, where individual viruses are combined.
 The envelope E2 proteins will be designed using structural and computational tools, developed by the PI
and his collaborators on projects with measles, flaviviruses, filovirus and alphaviruses, and incorporated into
vaccines developed in Dr. Weaver’s group. Together, we previously showed that a consensus E2 representing
several different VEEV strains could be incorporated into infectious virus. Even without optimization, the
consensus virus vaccine protected mice against a wild type (wt) strain of VEEV nearly as well as those
vaccinated with the same wt strain. Our first aim is to express and characterize multivalent, physicochemical
consensus proteins of the E2 glycoprotein that will represent both CHIKV and VEEV strains. These will be
optimized to bind antibodies against diverse alphaviruses and generate cross protective antibodies in mice. A
concurrent second aim is to introduce epitopes known to be the binding site for neutralizing antibodies into the
wt-E2 proteins of CHIKV and VEEV, expressed in the context of a whole virus, and determine the range of
protection these provide. In a third aim, the optimized E2 proteins will be incorporated into a novel whole virus
vaccine candidate based on the alphavirus Eilat (EILV), which replicates in mosquito but not mammalian cells.
Vaccinated mice will be challenged with diverse strains of CHICV, VEEV, and other alphaviruses. Dr. Weaver’s
group has shown that replacing the E proteins of EILV with those of CHIKV or VEEV can lead to new
diagnostic tools and an EILV/CHIKV vaccine candidate that remains restricted in its growth to insect cells but
generates protection against CHIKV. The anticipated outcome will be an optimized, broadly protective
vaccine against diverse alphavirus strains. The optimized, multivalent E2 protein...

## Key facts

- **NIH application ID:** 9988160
- **Project number:** 5R01AI137332-03
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** WERNER A BRAUN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $474,362
- **Award type:** 5
- **Project period:** 2018-08-21 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988160

## Citation

> US National Institutes of Health, RePORTER application 9988160, Mosaic Immunogens as Multivalent Alphavirus Vaccines (5R01AI137332-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9988160. Licensed CC0.

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