# The DKE-121 strain as a possible new Dengue virus serotype

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2020 · $235,938

## Abstract

Project Summary / Abstract
Dengue virus (DENV) causes dengue fever, the most prevalent arthropod-borne viral illness in humans. The
existing four serotypes of DENV (DENV1, DENV2, DENV3, and DENV4) cause an estimated 390 million
infections and at least 500,000 cases of Severe Dengue per year, which is a vascular leakage syndrome that
can result in hypotension, shock, and death. Currently, no specific therapy is available, and only one vaccine is
approved for use in humans (Dengvaxia®). This vaccine lacks efficacy in naïve individuals and appears to
promote disease in some recipients upon subsequent natural infection. This phenotype may be due in part to
suboptimal serotype responses and the phenomenon of antibody-dependent enhancement (ADE) of DENV
infection, where cross-reactive yet sub-neutralizing levels of antibody can promote virus entry and infection in
myeloid cells expressing activating Fcγ receptors. Accordingly, all of the current DENV vaccines in trials have a
goal of developing balanced and potently inhibitory tetravalent responses against the four serotypes of DENV.
Recently, a new strain of DENV (DKE-121) was isolated in Malaysia from an individual with Severe Dengue, with
up to 38, 37, 38, and 12% amino acid difference between DENV1, DENV2, DENV3, and DENV4 in the envelope
protein. This strain may represent a new DENV serotype (DENV5). The potential emergence of a new DENV
serotype could have major implications for existing tetravalent DENV vaccine platforms, which in theory, might
lack coverage. Given the possible significance of such a strain (and serotype), in this exploratory R21 application,
we propose to evaluate in detail the serological relatedness of DKE-121 to other DENV serotypes using a panel
of existing and newly-generated sera and monoclonal antibodies. In parallel, we will develop a new mouse model
of DKE-121 infection, which will be of utility to the field for assessing antibody activity, antibody cross-reactivity,
and pathogenesis in vivo. We hypothesize that the genetic differences between DKE-121 strain and existing
DENV serotypes will result in sufficient loss of serum cross-neutralization to classify this strain as a new DENV
serotype, which could have significant consequences for existing DENV vaccine platforms and trials if this or
related strains emerged.

## Key facts

- **NIH application ID:** 9861214
- **Project number:** 5R21AI145012-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Michael S Diamond
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $235,938
- **Award type:** 5
- **Project period:** 2019-02-05 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9861214

## Citation

> US National Institutes of Health, RePORTER application 9861214, The DKE-121 strain as a possible new Dengue virus serotype (5R21AI145012-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9861214. Licensed CC0.

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