# Multiplex serological assays to support arbovirus diagnosis, surveillance and vaccines

> **NIH NIH U24** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $413,630

## Abstract

Abstract
At a global level, ongoing ecological, environmental and demographic changes favor the survival and expansion
of several mosquito and tick species that transmit arboviruses. Aedes mosquito species that thrive in urban
environments created by humans are responsible for epidemics of several flaviviruses [dengue virus (DENV)
serotypes 1, 2, 3, 4; Zika virus (ZIKV); yellow fever virus (YFV)] and alphaviruses [chikungunya virus (CHIKV)
and Mayaro virus (MAYV)]. Laboratory-based diagnosis and surveillance for arboviruses is difficult because
most infected individuals are asymptomatic or develop a mild undifferentiated febrile illness. Serological assays
have been developed for the detection of recent or past arboviral infections, but the utility of these assays is
severely limited by antibody cross reactivity between related viruses. For example, when ZIKV emerged in many
regions of the Americas where greater than 80% of the population was dengue-immune, with current serological
assays, it was difficult, if not impossible, to identify infected individuals or monitor the spread of ZIKV at a
population level, and likewise to now detect new DENV infections in areas that experienced intense ZIKV
epidemics. Our studies over the past 10 years demonstrate that people exposed to flavivirus infections reliably
develop antibodies to epitopes that are unique to each flavivirus as well as cross-reactive antibodies. Using our
discoveries about the location of immunodominant virus type-specific epitopes, we have produced novel
recombinant antigens and demonstrated their utility for the type-specific diagnosis of arboviruses. Under
Specific Aim 1 of this proposal, we will build on these discoveries to develop a sample-sparing,
microsphere bead-based multiplex assay for the type-specific and sensitive detection of recent or past
arbovirus infections. Our initial studies will focus on 8 arboviruses transmitted by Aedes aegypti and Aedes
albopictus mosquitos because these viruses share a similar ecology and co-circulate in the same human
populations. At a second stage, we will expand the coverage of the assay to detect infections with other
arboviruses transmitted by other mosquito species and ticks. Several tetravalent DENV and ZIKV vaccines are
currently being evaluated in human clinical trials. While vaccine developers have relied on neutralizing
antibodies as a correlate of protection, recent results from clinical trials demonstrate that neutralizing antibodies
alone are a poor correlate of vaccine safety and efficacy. We have identified flavivirus type- and epitope-specific
antibody responses that are better predictors than neutralizing antibodies of vaccine safety and efficacy. Under
Specific aim 2 of this proposal, we will develop a sample-sparing microsphere-based assay for the
detection of epitope-specific vaccine-induced antibody responses that are correlated with protective
immunity to each of the DENV serotypes and ZIKV. The technological advances a...

## Key facts

- **NIH application ID:** 9986381
- **Project number:** 1U24AI152170-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Aravinda M. DeSilva
- **Activity code:** U24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $413,630
- **Award type:** 1
- **Project period:** 2020-05-11 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986381

## Citation

> US National Institutes of Health, RePORTER application 9986381, Multiplex serological assays to support arbovirus diagnosis, surveillance and vaccines (1U24AI152170-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9986381. Licensed CC0.

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