A Controlled Human Infection Model of Dengue

Summary

This study aims to conduct a safe human infection challenge using an attenuated serotype DEN3 dengue virus in adult volunteers. The clinical, viral and immune response characteristics of the model will be analysed to understand the pathophysiology of dengue fever. This data will be used to inform future studies, including a planned follow up study (DEN-CHIM-02) which will investigate the efficacy of an investigational dengue vaccine at protecting against DEN3 infection.

Study conditions that result in a safe, reproducible infection in ≥80% of research participants (attack rate) with the DEN3 challenge agent have been identified during studies conducted by our collaborators in the US. This includes the inoculum dose, safety monitoring, and necessary participant pre-screening to exclude prior Orthoflavivrus infection or vaccinations.

Study objectives are to:

1. Establish in seronegative volunteers in Singapore a safe DENV controlled human infection (CHI) model, with an infection rate of ≥80%, suitable for future studies of interventions.
2. Characterise the clinical, haematological and virological response following controlled inoculation of the attenuated DEN3 challenge agent.
3. Conduct deep immunophenotyping to understand the cellular, humoral and innate immune response to dengue infection.
4. Explore the longitudinal immune response in the 3 years after challenge, including following subsequent dengue vaccination.

Conditions

• Dengue

Interventions

OTHER

GMP-produced rDEN3delta30 virus

The challenge virus used in DEN-CHIM-01 study (rDEN3delta30) is produced by the National Institutes of Health (NIH). The rDEN3delta30 strain has been tested in seronegative participants in two challenge studies and with two inoculum doses: 10\^3 and 10\^4 PFU. The wildtype parent (wildtype DEN3 strain) of the rDEN3Δ30 challenge agent was originally obtained from an infected patient in 1978, in Sleman, Yogyakarta, Indonesia. The Sleman/78 strain was a naturally occurring, partially attenuated dengue virus (DENV) suitable for development as a challenge agent. The NIH team made a contiguous 30-nucleotide deletion in the 3' untranslated region of the wildtype DENV genome and produced recombinant DENV via cDNA clone (rDEN3delta30).

Sponsors & Collaborators

• A*Star

  collaborator OTHER

• Duke-NUS Graduate Medical School

  collaborator OTHER

• Lee Kong Chian School of Medicine, Nanyang Technological University

  collaborator UNKNOWN

• Tan Tock Seng Hospital

  lead OTHER

Principal Investigators

• Barnaby E Young, MB BChir, PhD · National Centre for Infectious Diseases (NCID)

Study Design

Allocation

NA

Purpose

OTHER

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

21 Years

Max Age

45 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2026-03-31

Primary Completion

2026-05-31

Completion

2029-04-30

Countries

• Singapore

Study Locations