High genomic diversity of dengue virus strains in Latin America and Asia-Pacific: insights from a phase 2 mosnodenvir clinical trial

Despite advances in disease monitoring, genomic surveillance of dengue virus (DENV) strains remains limited and regionally confined. The Phase 2 clinical trial (NCT05201794) of mosnodenvir prophylaxis conducted in endemic regions of Asia-Pacific and Latin America (2023–2024) provided a unique resource to assess genomic diversity of circulating DENVs. The study involved 411 dengue index cases (ICs). DENV serotypes were determined using RT-PCR. Whole-genome sequencing was conducted for a subset of ICs ( n = 150) representing DENV serotypes observed over time at 30 sites across 7 countries. Cocirculation of all four DENV serotypes was observed in both Latin America and Asia-Pacific regions. Overall, DENV-1 was the predominant serotype (51.1%), with significant geographical variations in genotype distribution: DENV-1 genotype V in Latin America versus genotypes I and IV in the Asia-Pacific region. We identified increased circulation of DENV-3 and DENV-4 strains in Latin America during 2023–2024. Time-resolved phylogenetic analyses show that the study captured a broad cross-section of contemporary DENV diversity circulating across Latin America and the Asia-Pacific region during 2023–2024. Our findings stress the importance of genomic surveillance for public health preparedness to mitigate dengue risk, highlighting a mosaic of local lineages and frequent virus (re)-introductions, which may trigger new epidemics.