Antibody Responses in Pediatric Dengue Indicate Emergence and Co-Circulation of DENV-3 Genotypes I and III in Myanmar and Orthoflavivirus Cross-Reactivity.

Dengue virus (DENV) remains a major public health concern in Southeast Asia, disproportionately affecting children. In Myanmar, DENV-3 Genotype III predominated before 2017, with Genotype I emerging thereafter. To assess the impact of this emergence on antibody responses, we analyzed paired acute and convalescent serum samples from 38 pediatric dengue patients collected between 2017 and 2019 alongside archived 2004 samples. Neutralization and in vitro antibody-dependent enhancement (ADE) were assessed against DENV-3 Genotypes I and III and other serotypes, with cross-reactivity analysis to Zika and Japanese encephalitis viruses. Samples from 2004 showed reduced neutralization and higher ADE for Genotype I, consistent with its absence at the time. In contrast, 2017-2019 samples exhibited comparable neutralization for both genotypes, with genotype- and year-dependent ADE differences, indicating that Genotype I emergence was associated with evolving functional antibody profiles. Hence, providing immunological evidence for continued co-circulation of DENV-3 Genotypes I and III in Myanmar. Future prospective pediatric cohort studies with continuous surveillance of circulating orthoflaviviruses and their genotypes, are essential to elucidate how pre-existing dengue immunity shapes genotype emergence and cross-orthoflavivirus immunity in endemic regions.