title: Dengue virus neutralizing antibody levels associated with protection from infection in thai cluster studies.
abstract: BACKGROUND
  Long-term homologous and temporary heterologous protection from dengue virus (DENV) infection may be mediated by neutralizing antibodies. However, neutralizing antibody titers (NTs) have not been clearly associated with protection from infection.
  
  
  RESULTS
  Data from two geographic cluster studies conducted in Kamphaeng Phet, Thailand were used for this analysis. In the first study (2004-2007), cluster investigations of 100-meter radius were triggered by DENV-infected index cases from a concurrent prospective cohort. Subjects between 6 months and 15 years old were evaluated for DENV infection at days 0 and 15 by DENV PCR and IgM ELISA. In the second study (2009-2012), clusters of 200-meter radius were triggered by DENV-infected index cases admitted to the provincial hospital. Subjects of any age ≥6 months were evaluated for DENV infection at days 0 and 14. In both studies, subjects who were DENV PCR positive at day 14/15 were considered to have been "susceptible" on day 0. Comparison subjects from houses in which someone had documented DENV infection, but the subject remained DENV negative at days 0 and 14/15, were considered "non-susceptible." Day 0 samples were presumed to be from just before virus exposure, and underwent plaque reduction neutralization testing (PRNT). Seventeen "susceptible" (six DENV-1, five DENV-2, and six DENV-4), and 32 "non-susceptible" (13 exposed to DENV-1, 10 DENV-2, and 9 DENV-4) subjects were evaluated. Comparing subjects exposed to the same serotype, receiver operating characteristic (ROC) curves identified homotypic PRNT titers of 11, 323 and 16 for DENV-1, -2 and -4, respectively, to differentiate "susceptible" from "non-susceptible" subjects.
  
  
  CONCLUSIONS
  PRNT titers were associated with protection from infection by DENV-1, -2 and -4. Protective NTs appeared to be serotype-dependent and may be higher for DENV-2 than other serotypes. These findings are relevant for both dengue epidemiology studies and vaccine development efforts.
authors.affiliation: Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: Darunee
authors.initials: D
authors.lastname: Buddhari
authors.affiliation: Department of Geography, University at Buffalo, Buffalo, New York, United States of America.
authors.forename: Jared
authors.initials: J
authors.lastname: Aldstadt
authors.affiliation: Department of Infectious Diseases, State University of New York at Syracuse, Syracuse, New York, United States of America.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Endy
authors.affiliation: Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors.forename: Anon
authors.initials: A
authors.lastname: Srikiatkhachorn
authors.affiliation: Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: Butsaya
authors.initials: B
authors.lastname: Thaisomboonsuk
authors.affiliation: Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: Chonticha
authors.initials: C
authors.lastname: Klungthong
authors.affiliation: Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: Ananda
authors.initials: A
authors.lastname: Nisalak
authors.affiliation: Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: Benjawan
authors.initials: B
authors.lastname: Khuntirat
authors.affiliation: Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Jarman
authors.affiliation: Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: Stefan
authors.initials: S
authors.lastname: Fernandez
authors.affiliation: Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Thomas
authors.affiliation: Department of Entomology and Nematology, University of California at Davis, Davis, California, United States of America; Fogarty International Center, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Scott
authors.affiliation: Institute for Immunology and Informatics, University of Rhode Island, Providence, Rhode Island, United States of America.
authors.forename: Alan L
authors.initials: AL
authors.lastname: Rothman
authors.affiliation: Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Yoon
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood* / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D015331:Cohort Studies; D003715:Dengue / Q000453:epidemiology / Q000276:immunology*; D003716:Dengue Virus / Q000145:classification / Q000276:immunology*; D004198:Disease Susceptibility / Q000276:immunology / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D009500:Neutralization Tests; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D013785:Thailand / Q000453:epidemiology; D010948:Viral Plaque Assay
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral