title: Preexisting neutralizing antibody responses distinguish clinically inapparent and apparent dengue virus infections in a Sri Lankan pediatric cohort.
abstract: Dengue viruses (DENVs) are mosquito-borne flaviviruses that infect humans. The clinical presentation of DENV infection ranges from inapparent infection to dengue hemorrhagic fever and dengue shock syndrome. We analyzed samples from a pediatric dengue cohort study in Sri Lanka to explore whether antibody responses differentiated clinically apparent infections from clinically inapparent infections. In DENV-naive individuals exposed to primary DENV infections, we observed no difference in the quantity or quality of acquired antibodies between inapparent and apparent infections. Children who experienced primary infections had broad, serotype-cross-neutralizing antibody responses that narrowed in breadth to a single serotype over a 12-month period after infection. In DENV immune children who were experiencing a repeat infection, we observed a strong association between preexisting neutralizing antibodies and clinical outcome. Notably, children with preexisting monospecific neutralizing antibody responses were more likely to develop fever than children with cross-neutralizing responses. Preexisting DENV neutralizing antibodies are correlated with protection from dengue disease.
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill.
authors.forename: Kizzmekia S
authors.initials: KS
authors.lastname: Corbett
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill Centre of Pathogen Evolution, University of Cambridge, United Kingdom.
authors.forename: Leah
authors.initials: L
authors.lastname: Katzelnick
authors.affiliation: Epidemiology Unit, Ministry of Health.
authors.forename: Hasitha
authors.initials: H
authors.lastname: Tissera
authors.affiliation: Epidemiology Unit, Ministry of Health.
authors.forename: Ananda
authors.initials: A
authors.lastname: Amerasinghe
authors.affiliation: Genetech Research Institute, Colombo, Sri Lanka.
authors.forename: Aruna Dharshan
authors.initials: AD
authors.lastname: de Silva
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill.
authors.forename: Aravinda M
authors.initials: AM
authors.lastname: de Silva
mesh_terms: D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology*; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003715:Dengue / Q000145:classification* / Q000453:epidemiology / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D011446:Prospective Studies; D012008:Recurrence; D016036:Seroepidemiologic Studies; D013188:Sri Lanka / Q000453:epidemiology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral
keywords: Sri Lanka; dengue fever; dengue virus; inapparent dengue; neutralizing antibody