Quantitative and qualitative differences in anti-Envelope IgG-secreting cells distinguish subclinical and hospitalized dengue in a Cambodian pediatric cohort
10 affiliations
- 1Institut Pasteur, Université Paris Cité, INSERM UMR1222, Antibodies in Therapy and Pathology, Paris, France
- 2Immunology Unit, Institut Pasteur du Cambodge, Pasteur Network, Phnom Penh, Cambodia
- 3Sorbonne University, Paris, France
- 4Epidemiology and Public Health Unit, Institut Pasteur du Cambodge, Pasteur Network, Phnom Penh, Cambodia
- 5Virology Unit, Institut Pasteur du Cambodge, Pasteur Network, Phnom Penh, Cambodia
- 6Institut Pasteur, Université Paris Cité, Bioinformatics and Biostatistics Hub, Paris, France
- 7Moderna, Inc., Cambridge, Massachusetts, United States of America
- 8Institut Pasteur, Université Paris Cité, CNRS UMR3528, Platform of Molecular Biophysics, Paris, France
- 9Institut Pasteur, Université Paris Cité, CNRS UMR 3569, Structural Virology, Paris, France
- 10Institut Pasteur, Université Paris Cité, CNRS UMR 2000, Ecology and Emergence of Arthropod-borne Pathogens, Paris, France
Abstract
Dengue virus (DENV) infection can result in outcomes ranging from subclinical infection to life-threatening illness, yet the antibody features mediating protection in humans remain poorly defined. Dengue virus envelope protein (E) forms homodimers on the virion surface and elicits both neutralizing and non-neutralizing antibodies from IgG-secreting cells (IgG-SC). How the developing antibody response at the monoclonal level contributes to protection is unknown. We profiled single IgG-SC responses in a Cambodian pediatric cohort by measuring affinity and serotype cross-reactivity of secreted antibodies from patients with subclinical or hospitalized dengue during acute DENV1 or DENV2 infection. Using droplet-based microfluidic imaging, we analyzed over 3,300 single IgG-SC. Hospitalized patients exhibited significantly lower numbers of IgG-SC, despite comparable IgG secretion rates and similar frequencies of DENV E-specific antibody-secreting cells relative to subclinical cases. In hospitalized patients, the affinity of IgG-SC for the DENV1 E-dimer was 3-fold lower compared to subclinical cases. Notably, antibodies recognizing quaternary epitopes—binding E-dimers but not monomers—were detected exclusively in subclinical cases, whereas hospitalized patients predominantly produced monomer-reactive antibodies. These findings suggest that dengue severity may be linked to the inefficient generation of sufficient numbers of high-affinity, broadly reactive antigen-specific IgG-SC during post-primary infection. Author summary: Most dengue virus infections cause mild illness or no symptoms, but some individuals progress to severe disease requiring hospitalization. Understanding why these outcomes differ is essential for improving vaccines and treatments. Antibodies play a central role in controlling dengue infection, but not all antibodies are equally protective. We examined antibody-producing cells generated during acute dengue infection in Cambodian children with subclinical infection or hospitalized dengue. Using a high-throughput single-cell microfluidic platform, we analyzed more than 3,300 individual IgG-secreting cells and measured the strength and specificity of the antibodies they produced. Hospitalized children generated similar proportions of dengue-specific antibody-producing cells, but they had fewer of these cells and their antibodies bound the viral envelope protein with lower affinity than those from children with subclinical infection. Importantly, only children with subclinical infection produced antibodies that recognized complex three-dimensional (quaternary) structures on the virus surface, which are thought to be among the most effective at neutralizing dengue virus. Our findings highlight the importance of monitoring antibody responses at the single-cell level and considering antigen structure in dengue vaccine design to promote protective immunity while reducing the risk of disease-associated responses.
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BibTeX
@article{trouchet2026quantitative,
title = {{Quantitative and qualitative differences in anti-Envelope IgG-secreting cells distinguish subclinical and hospitalized dengue in a Cambodian pediatric cohort}},
author = {Amandine Trouchet and Sokchea Lay and Matteo Broketa and Pablo Canales-Herrerias and Angga Perima and Bruno Iannascoli and Sotheary Sann and Borita Heng and Sowath Ly and Veasna Duong and Gaël A. Millot and Laura Walker and Patrick England and Giovanna Barba-Spaeth and Tineke Cantaert and Pierre Bruhns},
journal = {PLOS Pathogens},
year = {2026},
month = oct,
doi = {10.1371/journal.ppat.1014552},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014552},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Quantitative and qualitative differences in anti-Envelope IgG-secreting cells distinguish subclinical and hospitalized dengue in a Cambodian pediatric cohort
AU - Amandine Trouchet
AU - Sokchea Lay
AU - Matteo Broketa
AU - Pablo Canales-Herrerias
AU - Angga Perima
AU - Bruno Iannascoli
AU - Sotheary Sann
AU - Borita Heng
AU - Sowath Ly
AU - Veasna Duong
AU - Gaël A. Millot
AU - Laura Walker
AU - Patrick England
AU - Giovanna Barba-Spaeth
AU - Tineke Cantaert
AU - Pierre Bruhns
PY - 2026
DA - 2026/10/01
JO - PLOS Pathogens
DO - 10.1371/journal.ppat.1014552
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014552
AB - Dengue virus (DENV) infection can result in outcomes ranging from subclinical infection to life-threatening illness, yet the antibody features mediating protection in humans remain poorly defined. Dengue virus envelope protein (E) forms homodimers on the virion surface and elicits both neutralizing and non-neutralizing antibodies from IgG-secreting cells (IgG-SC). How the developing antibody response at the monoclonal level contributes to protection is unknown. We profiled single IgG-SC responses in a Cambodian pediatric cohort by measuring affinity and serotype cross-reactivity of secreted antibodies from patients with subclinical or hospitalized dengue during acute DENV1 or DENV2 infection. Using droplet-based microfluidic imaging, we analyzed over 3,300 single IgG-SC. Hospitalized patients exhibited significantly lower numbers of IgG-SC, despite comparable IgG secretion rates and similar frequencies of DENV E-specific antibody-secreting cells relative to subclinical cases. In hospitalized patients, the affinity of IgG-SC for the DENV1 E-dimer was 3-fold lower compared to subclinical cases. Notably, antibodies recognizing quaternary epitopes—binding E-dimers but not monomers—were detected exclusively in subclinical cases, whereas hospitalized patients predominantly produced monomer-reactive antibodies. These findings suggest that dengue severity may be linked to the inefficient generation of sufficient numbers of high-affinity, broadly reactive antigen-specific IgG-SC during post-primary infection. Author summary: Most dengue virus infections cause mild illness or no symptoms, but some individuals progress to severe disease requiring hospitalization. Understanding why these outcomes differ is essential for improving vaccines and treatments. Antibodies play a central role in controlling dengue infection, but not all antibodies are equally protective. We examined antibody-producing cells generated during acute dengue infection in Cambodian children with subclinical infection or hospitalized dengue. Using a high-throughput single-cell microfluidic platform, we analyzed more than 3,300 individual IgG-secreting cells and measured the strength and specificity of the antibodies they produced. Hospitalized children generated similar proportions of dengue-specific antibody-producing cells, but they had fewer of these cells and their antibodies bound the viral envelope protein with lower affinity than those from children with subclinical infection. Importantly, only children with subclinical infection produced antibodies that recognized complex three-dimensional (quaternary) structures on the virus surface, which are thought to be among the most effective at neutralizing dengue virus. Our findings highlight the importance of monitoring antibody responses at the single-cell level and considering antigen structure in dengue vaccine design to promote protective immunity while reducing the risk of disease-associated responses.
SN - 1553-7374
ER -