Protection against symptomatic dengue infection by neutralizing antibodies varies by infection history and infecting serotype

Protection against symptomatic dengue infection by neutralizing antibodies varies by infection history and infecting serotype

Dengue viruses (DENV1–4) are the most prevalent arboviruses in humans and a major public health concern. Understanding immune mechanisms that modulate DENV infection outcome is critical for vaccine development. Neutralizing antibodies (nAbs) are an essential component of the protective immune respon...

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Published in:Nature communications Vol. 15; no. 1; p. 382
Main Authors: Bos, Sandra, Graber, Aaron L., Cardona-Ospina, Jaime A., Duarte, Elias M., Zambrana, Jose Victor, Ruíz Salinas, Jorge A., Mercado-Hernandez, Reinaldo, Singh, Tulika, Katzelnick, Leah C., de Silva, Aravinda, Kuan, Guillermina, Balmaseda, Angel, Harris, Eva
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 09-01-2024
Nature Publishing Group
Nature Portfolio
Subjects:
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13/1
13/106
13/31
631/250/2152/2153/1291
631/250/255/2514
631/326/596/1413
692/308/3187
Animals
Antibodies
Antibodies, Neutralizing
Antibody response
Child
Chlorocebus aethiops
Cohort Studies
Coinfection
DC-SIGN protein
Dengue - prevention & control
Dengue fever
Humanities and Social Sciences
Humans
Immune response
Immune system
Infections
Maturation
multidisciplinary
Neutralizing
Pediatrics
Public health
Science
Science (multidisciplinary)
Serogroup
Substrates
Vaccine development
Vaccines
Vector-borne diseases
Vero Cells
Virions
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Summary:Dengue viruses (DENV1–4) are the most prevalent arboviruses in humans and a major public health concern. Understanding immune mechanisms that modulate DENV infection outcome is critical for vaccine development. Neutralizing antibodies (nAbs) are an essential component of the protective immune response, yet their measurement often relies on a single cellular substrate and partially mature virions, which does not capture the full breadth of neutralizing activity and may lead to biased estimations of nAb potency. Here, we analyze 125 samples collected after one or more DENV infections but prior to subsequent symptomatic or inapparent DENV1, DENV2, or DENV3 infections from a long-standing pediatric cohort study in Nicaragua. By assessing nAb responses using Vero cells with or without DC-SIGN and with mature or partially mature virions, we find that nAb potency and the protective NT50 cutoff are greatly influenced by cell substrate and virion maturation state. Additionally, the correlation between nAb titer and protection from disease depends on prior infection history and infecting serotype. Finally, we uncover variations in nAb composition that contribute to protection from symptomatic infection differently after primary and secondary prior infection. These findings have important implications for identifying antibody correlates of protection for vaccines and natural infections. There is still a need to improve understanding of dengue-specific immunity. Here, by analyzing the antibody response in a pediatric cohort the authors show that the protective capacity of neutralizing antibodies depends on infection history and serotype, but its estimation varies by assay condition and virion maturation.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-023-44330-8