International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2026
Broadly cross-reactive neutralizing and enhancing antibody responses to dengue, Japanese encephalitis and Zika viruses in sera from Vietnamese pediatric dengue cases.
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Raekiansyah Muhareva, Ngwe Tun Mya Myat, Balingit Jean Claude, Nguyen Thi Thanh Ngan, Nguyen Thanh Vu, Kapandji Merveille, Takamatsu Yuki, Urano Takeshi, Le Thi Quynh Mai, Hasebe Futoshi, Morita Kouichi
Аннотация
OBJECTIVES: Understanding the balance between protective and pathogenic antibody responses is central to dengue immunology and flavivirus vaccine development.
METHODS: Fifty paired acute and convalescent serum samples from pediatric dengue patients in southern Vietnam (2015-2017) were analyzed, including primary and secondary infections across a spectrum of disease severity. Primary and secondary DENV infections were classified using an in-house validated DENV IgG ELISA. Neutralizing antibody (NAb) titers and antibody-dependent enhancement (ADE) activities were evaluated against dengue virus the four serotypes (DENV), Japanese encephalitis virus (JEV) and ZIKA (ZIKV) using single-round infectious particles (SRIPs).
RESULTS: Neutralizing antibody (NAb) responses were detected against all DENV serotypes and were highest against DENV-1. NAb titers increased during convalescence and were generally higher in secondary than primary infections. Higher NAb titers were also observed in convalescent sera from DSS cases compared with other clinical groups. ADE activity was most pronounced against DENV-2 and was lowest against DENV-4, while Peak enhancement titers (PET) were higher in convalescent samples, secondary infections, and DSS cases, and were positively correlated with NAb titers. Additionally, higher enhancement activity was observed in sera from DSS cases than in those from milder disease categories. Cross-reactive neutralizing and enhancing antibodies against JEV and ZIKV were also detected, with stronger enhancement observed against ZIKV.
CONCLUSION: Heightened neutralizing immunity in secondary and severe dengue is accompanied by expanded enhancement potential, indicating an expanded, cross-reactive immune response driven by immune activation upon infection. The coexistence of protective and enhancing antibodies may contribute both to viral control and to immunopathogenesis during subsequent flavivirus infections.
METHODS: Fifty paired acute and convalescent serum samples from pediatric dengue patients in southern Vietnam (2015-2017) were analyzed, including primary and secondary infections across a spectrum of disease severity. Primary and secondary DENV infections were classified using an in-house validated DENV IgG ELISA. Neutralizing antibody (NAb) titers and antibody-dependent enhancement (ADE) activities were evaluated against dengue virus the four serotypes (DENV), Japanese encephalitis virus (JEV) and ZIKA (ZIKV) using single-round infectious particles (SRIPs).
RESULTS: Neutralizing antibody (NAb) responses were detected against all DENV serotypes and were highest against DENV-1. NAb titers increased during convalescence and were generally higher in secondary than primary infections. Higher NAb titers were also observed in convalescent sera from DSS cases compared with other clinical groups. ADE activity was most pronounced against DENV-2 and was lowest against DENV-4, while Peak enhancement titers (PET) were higher in convalescent samples, secondary infections, and DSS cases, and were positively correlated with NAb titers. Additionally, higher enhancement activity was observed in sera from DSS cases than in those from milder disease categories. Cross-reactive neutralizing and enhancing antibodies against JEV and ZIKV were also detected, with stronger enhancement observed against ZIKV.
CONCLUSION: Heightened neutralizing immunity in secondary and severe dengue is accompanied by expanded enhancement potential, indicating an expanded, cross-reactive immune response driven by immune activation upon infection. The coexistence of protective and enhancing antibodies may contribute both to viral control and to immunopathogenesis during subsequent flavivirus infections.