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Dengue virus neutralizing antibody levels associated with protection from infection in thai cluster studies.

Buddhari D, Aldstadt J, Endy TP, Srikiatkhachorn A, Thaisomboonsuk B, Klungthong C, Nisalak A, Khuntirat B, Jarman RG, Fernandez S, Thomas SJ, Scott TW, Rothman AL, Yoon IK - PLoS Negl Trop Dis (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.

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.

Methodology/principal findings: 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/significance: 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.

No MeSH data available.


Related in: MedlinePlus

Pre-exposure neutralizing antibody titers (NTs) in dengue virus serotype 1 (DENV-1) “susceptible” and “non-susceptible subjects.Graphs show: (a) six DENV-1 PCR positive (“susceptible”) subjects; (b) 13 DENV-1 PCR negative (“non-susceptible”) subjects. NTs for each subject are against the reference strains for DENV-1, -2, -3, -4 and Japanese encephalitis virus (JEV) (red, blue, green, purple and orange, respectively).
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pntd-0003230-g001: Pre-exposure neutralizing antibody titers (NTs) in dengue virus serotype 1 (DENV-1) “susceptible” and “non-susceptible subjects.Graphs show: (a) six DENV-1 PCR positive (“susceptible”) subjects; (b) 13 DENV-1 PCR negative (“non-susceptible”) subjects. NTs for each subject are against the reference strains for DENV-1, -2, -3, -4 and Japanese encephalitis virus (JEV) (red, blue, green, purple and orange, respectively).

Mentions: Altogether, 49 subjects were available for analysis: 17 PCR positive “susceptible” subjects (six DENV-1, five DENV-2 and six DENV-4), and 32 PCR negative “non-susceptible” subjects (13 from DENV-1 clusters, 10 DENV-2 and 9 DENV-4). Table 1 lists characteristics of the 49 subjects. Figures 1, 2 and 3 show bar graphs of day 0 NTs for each subject. Seven “susceptible” compared with three “non-susceptible” subjects had DENV naïve NT profiles on day 0 (odds ratio = 6.460 [95% CI 1.198, 46.302]).


Dengue virus neutralizing antibody levels associated with protection from infection in thai cluster studies.

Buddhari D, Aldstadt J, Endy TP, Srikiatkhachorn A, Thaisomboonsuk B, Klungthong C, Nisalak A, Khuntirat B, Jarman RG, Fernandez S, Thomas SJ, Scott TW, Rothman AL, Yoon IK - PLoS Negl Trop Dis (2014)

Pre-exposure neutralizing antibody titers (NTs) in dengue virus serotype 1 (DENV-1) “susceptible” and “non-susceptible subjects.Graphs show: (a) six DENV-1 PCR positive (“susceptible”) subjects; (b) 13 DENV-1 PCR negative (“non-susceptible”) subjects. NTs for each subject are against the reference strains for DENV-1, -2, -3, -4 and Japanese encephalitis virus (JEV) (red, blue, green, purple and orange, respectively).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4199527&req=5

pntd-0003230-g001: Pre-exposure neutralizing antibody titers (NTs) in dengue virus serotype 1 (DENV-1) “susceptible” and “non-susceptible subjects.Graphs show: (a) six DENV-1 PCR positive (“susceptible”) subjects; (b) 13 DENV-1 PCR negative (“non-susceptible”) subjects. NTs for each subject are against the reference strains for DENV-1, -2, -3, -4 and Japanese encephalitis virus (JEV) (red, blue, green, purple and orange, respectively).
Mentions: Altogether, 49 subjects were available for analysis: 17 PCR positive “susceptible” subjects (six DENV-1, five DENV-2 and six DENV-4), and 32 PCR negative “non-susceptible” subjects (13 from DENV-1 clusters, 10 DENV-2 and 9 DENV-4). Table 1 lists characteristics of the 49 subjects. Figures 1, 2 and 3 show bar graphs of day 0 NTs for each subject. Seven “susceptible” compared with three “non-susceptible” subjects had DENV naïve NT profiles on day 0 (odds ratio = 6.460 [95% CI 1.198, 46.302]).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.

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.

Methodology/principal findings: 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/significance: 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.

No MeSH data available.


Related in: MedlinePlus