# Immune responses associated with severe disease in patients with primary dengue infection

> **NIH NIH R01** · EMORY UNIVERSITY · 2024 · $605,852

## Abstract

SUMMARY
Dengue is an emerging global public health threat. Decades of extensive research undertaken primarily in
dengue-endemic regions has resulted in the prevailing consensus that secondary infections and antibody-
dependent enhancement (ADE) are pivotal in the pathogenesis of severe dengue disease. While previous
research showed severe outcomes in naïve populations, our understanding of the mechanisms underpinning
the pathogenesis of the severe disease during primary dengue infections, and how it diverges from secondary
infections, remains limited. Bridging this knowledge gap is vital, given that dengue is spreading to new areas
with substantial naïve population, compounded by lack of vaccines that can generate balanced immune
response or distinct clinical management protocols for primary versus secondary dengue. Hence, the specific
aims outlined below will provide comprehensive studies in India, where we find substantial burden of severe
disease by primary infections, to concurrently scrutinize the disease spectrum in primary and secondary dengue,
to elucidate pathogenesis. Aim 1, Determine the differences in innate immune responses during severe primary
and secondary dengue infection. Aim 2, Evaluate differences in the magnitude, function, and post-translational
modification of dengue-specific antibodies during severe primary and secondary dengue infection. Aim 3,
Determine how dengue specific CD8+ and CD4+ T cell responses differ between severe primary and secondary
dengue infection. The proposed studies encompass in-depth analyses of innate, inflammatory, antibody, and T-
cell responses, alongside virological aspects, and their intricate interplay. Leveraging state-of-the-art tools and
technologies such as viral inclusive s\cRNA seq, Fc glycosylation, and human monoclonals, the research will be
primarily conducted in India utilizing samples from patient cohorts there. The joint ICGEB-Emory Vaccine Center
laboratory in New Delhi, that we developed over several years to enhance human immunology research capacity,
stands as an invaluable and unique resource for this endeavor.

## Key facts

- **NIH application ID:** 11000009
- **Project number:** 1R01AI186371-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** MURALI KRISHNA KAJA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $605,852
- **Award type:** 1
- **Project period:** 2024-09-10 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11000009

## Citation

> US National Institutes of Health, RePORTER application 11000009, Immune responses associated with severe disease in patients with primary dengue infection (1R01AI186371-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11000009. Licensed CC0.

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