Dengue NS1 Antibodies Are Associated With Clearance of Viral Nonstructural Protein-1

Author:

Premazzi Papa Michelle1,Mendoza-Torres Evelyn2,Sun Peifang3,Encinales Liliana4,Goulet Joseph5,Defang Gabriel3,Vihasi Jani6,Cheng Ying7,Suchowiecki Karol8,Rosales Wendy2,Amdur Richard9,Porras-Ramirez Alexandra10,Rico-Mendoza Alejandro10,Herrera Gomez Carlos8,Nicholes Samuel1,Zuluaga Ivan11,Halstead Liam8,Halstead Scott12,Simon Gary8,Porter Kevin312,Lynch Rebecca M1ORCID,Chang Aileen Y18

Affiliation:

1. Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University , Washington, District of Columbia , USA

2. Grupo de Investigación Avanzada en Biomedicina, Universidad Libre de Colombia , Barranquilla, Atlántico , Colombia

3. Directorate for Defense Infectious Diseases, Naval Medical Research Center , Silver Spring, Maryland , USA

4. Department of Medicine, Allied Research Society Colombia , Barranquilla, Atlántico , Colombia

5. Department of Emergency Medicine, Yale School of Medicine , West Haven, Connecticut , USA

6. Henry Jackson Foundation , Bethesda, Maryland , USA

7. Leidos , Reston, Virginia , USA

8. Department of Medicine, School of Medicine and Health Sciences, The George Washington University , Washington, District of Columbia , USA

9. Department of Quantitative Intelligence, Institute for Health Systems Science, Feinstein Institutes for Medical Research , Manhasset, New York , USA

10. Grupo de Medicina Comunitaria y Salud Colectiva, Universidad El Bosque , Bogotá , Colombia

11. Clínica Iberoamérica, Universidad Libre de Barranquilla , Barranquilla, Atlántico , Colombia

12. Department of Medicine, Infectious Diseases Division, Uniformed Services University , Bethesda, Maryland , USA

Abstract

Abstract Background Dengue vascular permeability syndrome is the primary cause of death in severe dengue infections. The protective versus potentially pathogenic role of dengue nonstructural protein-1 (NS1) antibodies are not well understood. The main goal of this analysis was to characterize the relationship between free NS1 concentration and NS1 antibody titers in primary and secondary dengue infection to better understand the presence and duration of NS1 antibody complexes in clinical dengue infections. Methods Hospitalized participants with acute dengue infection were recruited from Northern Colombia between 2018 and 2020. Symptom assessment, including dengue signs and symptoms, chart review, and blood collection, was performed. Primary versus secondary dengue was assessed serologically. NS1 titers and anti-NS1 antibodies were measured daily. Results Patients with secondary infection had higher antibody titers than those in primary infection, and there was a negative correlation between anti-NS1 antibody titer and NS1 protein. We demonstrate that in a subset of secondary infection, there were indeed NS1 antigen-antibody complexes on the admission day during the febrile phase that were not detectable by the recovery phase. Furthermore, dengue infection status was associated with higher circulating sialidases. Discussion The negative correlation between antibody and protein suggests that antibodies may play a role in clearing this viral protein.

Funder

National Center for Advancing Translational Sciences

National Institutes of Health

Publisher

Oxford University Press (OUP)

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