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Neutralizing antibody titers against dengue virus correlate with protection from symptomatic infection in a longitudinal cohort.
Proc Natl Acad Sci U S A. 2016 Jan 19; 113(3):728-33.PN

Abstract

The four dengue virus serotypes (DENV1-4) are mosquito-borne flaviviruses that infect ∼ 390 million people annually; up to 100 million infections are symptomatic, and 500,000 cases progress to severe disease. Exposure to a heterologous DENV serotype, the specific infecting DENV strains, and the interval of time between infections, as well as age, ethnicity, genetic polymorphisms, and comorbidities of the host, are all risk factors for severe dengue. In contrast, neutralizing antibodies (NAbs) are thought to provide long-lived protection against symptomatic infection and severe dengue. The objective of dengue vaccines is to provide balanced protection against all DENV serotypes simultaneously. However, the association between homotypic and heterotypic NAb titers and protection against symptomatic infection remains poorly understood. Here, we demonstrate that the titer of preinfection cross-reactive NAbs correlates with reduced likelihood of symptomatic secondary infection in a longitudinal pediatric dengue cohort in Nicaragua. The protective effect of NAb titers on infection outcome remained significant when controlled for age, number of years between infections, and epidemic force, as well as with relaxed or more stringent criteria for defining inapparent DENV infections. Further, individuals with higher NAb titers immediately after primary infection had delayed symptomatic infections compared with those with lower titers. However, overall NAb titers increased modestly in magnitude and remained serotype cross-reactive in the years between infections, possibly due to reexposure. These findings establish that anti-DENV NAb titers correlate with reduced probability of symptomatic DENV infection and provide insights into longitudinal characteristics of antibody-mediated immunity to DENV in an endemic setting.

Authors+Show Affiliations

Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, CA 94720-3370; Centre for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, United Kingdom;Centre for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, United Kingdom;Sustainable Sciences Institute, Managua, Nicaragua;Laboratorio Nacional de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, Nicaragua.Centre for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, United Kingdom; eharris@berkeley.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26729879

Citation

Katzelnick, Leah C., et al. "Neutralizing Antibody Titers Against Dengue Virus Correlate With Protection From Symptomatic Infection in a Longitudinal Cohort." Proceedings of the National Academy of Sciences of the United States of America, vol. 113, no. 3, 2016, pp. 728-33.
Katzelnick LC, Montoya M, Gresh L, et al. Neutralizing antibody titers against dengue virus correlate with protection from symptomatic infection in a longitudinal cohort. Proc Natl Acad Sci U S A. 2016;113(3):728-33.
Katzelnick, L. C., Montoya, M., Gresh, L., Balmaseda, A., & Harris, E. (2016). Neutralizing antibody titers against dengue virus correlate with protection from symptomatic infection in a longitudinal cohort. Proceedings of the National Academy of Sciences of the United States of America, 113(3), 728-33. https://doi.org/10.1073/pnas.1522136113
Katzelnick LC, et al. Neutralizing Antibody Titers Against Dengue Virus Correlate With Protection From Symptomatic Infection in a Longitudinal Cohort. Proc Natl Acad Sci U S A. 2016 Jan 19;113(3):728-33. PubMed PMID: 26729879.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neutralizing antibody titers against dengue virus correlate with protection from symptomatic infection in a longitudinal cohort. AU - Katzelnick,Leah C, AU - Montoya,Magelda, AU - Gresh,Lionel, AU - Balmaseda,Angel, AU - Harris,Eva, Y1 - 2016/01/04/ PY - 2016/1/6/entrez PY - 2016/1/6/pubmed PY - 2016/6/15/medline KW - Nicaragua KW - cohort study KW - dengue virus KW - neutralizing antibodies KW - protection SP - 728 EP - 33 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 113 IS - 3 N2 - The four dengue virus serotypes (DENV1-4) are mosquito-borne flaviviruses that infect ∼ 390 million people annually; up to 100 million infections are symptomatic, and 500,000 cases progress to severe disease. Exposure to a heterologous DENV serotype, the specific infecting DENV strains, and the interval of time between infections, as well as age, ethnicity, genetic polymorphisms, and comorbidities of the host, are all risk factors for severe dengue. In contrast, neutralizing antibodies (NAbs) are thought to provide long-lived protection against symptomatic infection and severe dengue. The objective of dengue vaccines is to provide balanced protection against all DENV serotypes simultaneously. However, the association between homotypic and heterotypic NAb titers and protection against symptomatic infection remains poorly understood. Here, we demonstrate that the titer of preinfection cross-reactive NAbs correlates with reduced likelihood of symptomatic secondary infection in a longitudinal pediatric dengue cohort in Nicaragua. The protective effect of NAb titers on infection outcome remained significant when controlled for age, number of years between infections, and epidemic force, as well as with relaxed or more stringent criteria for defining inapparent DENV infections. Further, individuals with higher NAb titers immediately after primary infection had delayed symptomatic infections compared with those with lower titers. However, overall NAb titers increased modestly in magnitude and remained serotype cross-reactive in the years between infections, possibly due to reexposure. These findings establish that anti-DENV NAb titers correlate with reduced probability of symptomatic DENV infection and provide insights into longitudinal characteristics of antibody-mediated immunity to DENV in an endemic setting. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/26729879/Neutralizing_antibody_titers_against_dengue_virus_correlate_with_protection_from_symptomatic_infection_in_a_longitudinal_cohort_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=26729879 DB - PRIME DP - Unbound Medicine ER -