AI Article Synopsis

  • - The study evaluated the safety and immune response of a low-dose DENV-3 challenge model in nine healthy individuals, following subcutaneous inoculation with an attenuated dengue virus strain.
  • - All participants developed detectable viral RNA within a week, with symptoms like fever, rash, and laboratory abnormalities indicating mild-to-moderate dengue.
  • - Immunological responses, including seroconversion and memory T cell activation, were evident within 14 days, and the severity of clinical symptoms correlated with the peak viral load in each participant.

Article Abstract

Dengue human infection models present an opportunity to explore the potential of a vaccine, anti-viral or immuno-compound for clinical benefit in a controlled setting. Here we report the outcome of a phase 1 open-label assessment of a low-dose dengue virus 3 (DENV-3) challenge model (NCT04298138), in which nine participants received a subcutaneous inoculation with 0.5 ml of a 1.4 × 10 plaque-forming unit per ml suspension of the attenuated DENV-3 strain CH53489. The primary and secondary endpoints of the study were to assess the safety of this DENV-3 strain in healthy flavivirus-seronegative individuals. All participants developed RNAaemia within 7 days after inoculation with peak titre ranging from 3.13 × 10 to 7.02 × 10 genome equivalents per ml. Solicited symptoms such as fever and rash, clinical laboratory abnormalities such as lymphopenia and thrombocytopenia, and self-reported symptoms such as myalgia were consistent with mild-to-moderate dengue in all volunteers. DENV-3-specific seroconversion and memory T cell responses were observed within 14 days after inoculation as assessed by enzyme-linked immunosorbent assay and interferon-gamma-based enzyme-linked immunospot. RNA sequencing and serum cytokine analysis revealed anti-viral responses that overlapped with the period of viraemia. The magnitude and frequency of clinical and immunologic endpoints correlated with an individual's peak viral titre.

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Source
http://dx.doi.org/10.1038/s41564-024-01668-zDOI Listing

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