Genetic diversity of dengue virus circulating in the Philippines (2014-2019) and comparison with dengue vaccine strains.

Dengue virus has four distinct serotypes and the genetic diversity within each of the four serotypes contribute to its complexity. An important aspect of dengue molecular evolutionary studies has been the dissection of the extent and structure of genetic variation among major genotypes within each serotype. It is important to understand the role of dengue genetic variability and its potential role and impact in the effectiveness of the dengue vaccine. Demographic data and blood were collected from patients seen at a tertiary hospital in the Philippines and clinically diagnosed with dengue from 2014-2019. Dengue virus (DENV) RT-PCR was used to confirm infection and positive samples underwent whole genome sequencing. Phylogenetic analysis was performed on 127 samples (25 DENV-1, 19 DENV-2, 70 DENV-3, and 13 DENV-4). We observed a serotype shift in 2014 and 2022. We detected the following genotypes per serotype for the wild-type (WT) DENV sequences: genotype IV (DENV-1), cosmopolitan (DENV-2), genotype I (DENV-3) and genotype IIa (DENV-4). WT DENV belonged to different genotypes versus the QDENGA strains and except for DENV-4, belonged to different genotypes versus the Dengvaxia strains. Comparing Dengvaxia vaccine sequences with WT DENV, we observed 23, 24, 34, and 9 positions with amino acid changes in the entire envelope protein, with 1, 5, 1, and 2 positions with amino acid changes identified among the important human monoclonal antibodies (mAbs) targeted epitope positions. We detected 24, 25, 36 and 12 positions with amino acid changes in the E protein with 0, 5, 1, and 2 positions with amino acid changes among the important mAbs targeted epitope positions for DENV-1, DENV-2, DENV-3, and DENV-4, respectively when comparing QDENGA vaccine sequences with the WT DENV. We showed low genotype complexity, genetically distinct clades and local evolution for DENV circulating in the Philippines.