Detection of Anti-ZIKV NS1 IgA, IgM, and Combined IgA/IgM and Identification of IL-4 and IL-10 as Potential Biomarkers for Early ZIKV and DENV Infections in Hyperendemic Regions, Thailand

Petphong, Vajee; Kosoltanapiwat, Nathamon; Limkittikul, Kriengsak; Maneekan, Pannamas; Chatchen, Supawat; Jittmittraphap, Akanitt; Sriburin, Pimolpachr; Chattanadee, Siriporn; Leaungwutiwong, Pornsawan

doi:10.3390/tropicalmed8050284

Cited by 2 publications

(3 citation statements)

References 70 publications

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“…That role may contribute to avoid potential disease enhancement during a secondary flavivirus exposure, due to generation of wide CR DENV MBC as consequence of a suboptimal priming. In contrast to the total IgG, no animals had detectable anti-ZIKV-NS1 IgG Abs at baseline, indicating that those Abs are very specific, supporting the efforts to use this protein as a diagnostic marker (Castro-Trujillo et al, 2023; Guzman et al, 2010; Petphong et al, 2023; Vazquez et al, 1995), but also considering the antigen as a target for vaccination. However, removing CD4 + T cells prior to primary infection resulted in a significant increase in DENV anti-NS1 Abs durability.…”

Section: Discussionmentioning

confidence: 73%

“…Most humoral immunity epitopes are located within the domains of the DENV envelope (E) protein, while cellular immunity epitopes are located on the NS proteins (Pinheiro et al, 2021; Rothman, 2010). Additionally, the NS1 protein is particularly interesting and unique, as it is a protein produced and secreted during viral replication, which make it highly immunogenic (Zhang et al, 2023) inducing significant levels of anti-NS1 Abs in DENV-and ZIKV-infected individuals (Aquino et al, 2023; Castro-Trujillo et al, 2023; Churdboonchart et al, 1991; Costa et al, 2007; Petphong et al, 2023). It is documented that DENV E and NS1 proteins equally score 4 – out of the 10 proteins – in an immunogenicity score (Weiskopf et al, 2016), and some reports have pointed NS1 as a target antigen for the development of DENV vaccines (Costa et al, 2007; Costa et al, 2006; Henchal et al, 1988; Wan et al, 2014), while others suggest a role for this protein in the pathogenesis (Perera et al, 2024; Shu et al, 2000; Zhang et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

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CD4+ T Cell Depletion Before Primary Dengue and/or Secondary Zika Infection Reveals Mechanistic Correlates of Antibody Functionality in Rhesus Macaques

Serrano-Collazo,

Miranda,

Cruz

et al. 2024

Preprint

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Dengue (DENV) virus and Zika virus (ZIKV) are two flaviviruses of major public health concern. One drawback designing effective vaccines is our limited understanding of the mechanisms ruling protection or harm among DENV serotypes, or between DENV and ZIKV. Here, we depleted rhesus macaques of CD4+T cellsin vivobefore primary DENV infection and/or secondary ZIKV challenge to recreate a sub-optimal priming of the humoral immune response. Our results support that CD4+T cells are needed to induce a quantitative and type-specific effective humoral immune response against primary DENV, but also against secondary ZIKV in DENV-experimented subjects. Our results also indicate a limited contribution of the DENV-Memory B cells to anti-ZIKV response. Furthermore, our results suggest that a suboptimal B cell priming during a primary DENV infection does differentially impact different antibody (Abs) properties. While binding or neutralization of ZIKV or DENV during a subsequent exposure to ZIKV is not affected by the lack of CD4+T - B cells interaction during a primary DENV infection, that interaction is critical to guarantee the Abs specificity. Also, we found that depleting CD4+T cells before DENV primary infection but not before ZIKV challenge significantly increases Abs cross-reactivity against DENV-EDIII domain and DENV-NS1 protein but not against ZIKV-EDIII domain or NS1 protein. Furthermore, there was more cross-reactivity among the DENV-NS1 proteins than against DENV-EDIII domains, suggesting that during a primary DENV infection CD4+T cells have a different weight in the responses against EDIII domain and NS1 protein. The proper Abs binding and neutralization with increased cross-reactivity profile was associated with limited frequency of circulating peripheral T helper cells (pTfh) with T helper 1 phenotype (CD4+/CXCR5+/CXCR3+) and expressing markers related to B cell activation (CXCR5+/CXCR3+/PD-1+/ICOS+) in the group depleted of CD4+T cells only before primary DENV infection. However, memory B cells – but not Antibody Secreting Cells (ASC) activation 7 days after the infection – positively correlate with those two populations of pTfh. Finally, when Abs cross-reactivity values were incorporated in a Principal Component Analysis (PCA), the DENV-CD4+T depleted group separates from the other two groups with similar Abs binding and neutralization profiles. Our result strongly suggests that during a heterologous sequential DENV/ZIKV infections Abs binding, and neutralization, may be regulated by different factors than their specificity. Before, the induction of cross-neutralizing Abs has been described in the context of secondary DENV infection. Here, for the first time, we are reproducing the experimental conditions leading to the generation of such Abs populationin vivo. In summary, we show that suboptimal immune priming during a primary flavivirus infection has functional consequences during a secondary heterologous infection. These results have huge implications understanding the immune response to DENV vaccines (and maybe ZIKV), including why an optimal vaccine or natural-induced neutralizing response not necessarily protects or enhances pathogenesis during a subsequent natural heterologous exposure.

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Section: Discussionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

CD4+ T Cell Depletion Before Primary Dengue and/or Secondary Zika Infection Reveals Mechanistic Correlates of Antibody Functionality in Rhesus Macaques

Serrano-Collazo,

Miranda,

Cruz

et al. 2024

Preprint

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“…A modo de conclusión, es posible indicar que la combinación 11 del estudio comprendía una proteína C reactiva negativa y plaquetopenia fue lo más relevante en el estudio, y presentó mayor validez como posible herramienta para el diagnóstico (20)(21)(22)(23)(24) . Por ello se considera una opción atractiva para el diagnóstico presuntivo de dengue en la sala de urgencias en la que el paciente fue recibido.…”

Section: Comounclassified

Validez de herramientas diagnósticas en pacientes pediátricos hospitalizados con diagnóstico presuntivo de dengue en un Hospital de Referencia de Paraguay

Agüero Echeverría,

Arza Fernández,

Aguilar

et al. 2024

An. Fac. Cienc. Méd. (Asunción)

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Introducción: El dengue es la enfermedad arboviral más común en los seres humanos. Un diagnóstico temprano y preciso del dengue puede respaldar el manejo clínico, la vigilancia y el control de la enfermedad y es fundamental, por ello en el diagnóstico del dengue es importante contar con pautas clínicas y epidemiológicas que permitan la identificación oportuna y una conducta terapéutica adecuada. Objetivos: Evaluar la validez de herramientas diagnósticas en pacientes pediátricos hospitalizados con diagnóstico presuntivo de dengue en un Hospital de Referencia de Paraguay durante los años de 2012 a 2020. Materiales y métodos: Estudio analítico de tipo observacional, retrospectivo correspondientes a pacientes pediátricos (0 a 18 años) internados en el Hospital de Referencia de Paraguay el periodo enero 2012 a julio 2020 con diagnostico presuntivo de dengue al ingreso. Se realizó́ un análisis bivariado relacionando las frecuencias de 20 grupos de criterios diagnósticos combinados y 3 criterios diagnósticos aislados (OMS 2009, nexo epidemiológico y antigenemia NS1 para dengue) con el gold standard de diagnóstico que fue la conversión serológica. Resultados: Participaron del estudio 342 sujetos. EL 44% tenía edad escolar y 70% tenía 5 años o más. El 52,76% (191) fueron masculinos. Se encontraron desnutrición y sobrepeso en el 13% y 2%, respectivamente. La combinación de proteína C reactiva con plaquetopenia se encontró́ en 0.45% de los pacientes sin dengue y en el 6% de los pacientes con diagnóstico final de dengue (p=0.004). Conclusión: Este resultado aporta la alternativa de uso de una combinación sencilla de exámenes de laboratorio que puede replicarse en salas de urgencias como en salas de internación en un primer contacto con pacientes febriles con sospecha de fiebre dengue.

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Detection of Anti-ZIKV NS1 IgA, IgM, and Combined IgA/IgM and Identification of IL-4 and IL-10 as Potential Biomarkers for Early ZIKV and DENV Infections in Hyperendemic Regions, Thailand

Cited by 2 publications

References 70 publications

CD4+ T Cell Depletion Before Primary Dengue and/or Secondary Zika Infection Reveals Mechanistic Correlates of Antibody Functionality in Rhesus Macaques

CD4+ T Cell Depletion Before Primary Dengue and/or Secondary Zika Infection Reveals Mechanistic Correlates of Antibody Functionality in Rhesus Macaques

Validez de herramientas diagnósticas en pacientes pediátricos hospitalizados con diagnóstico presuntivo de dengue en un Hospital de Referencia de Paraguay

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