# The Genetic Evolution of DENV2 in the French Territories of the Americas: A Retrospective Study from the 2000s to the 2024 Epidemic, Including a Comparison of Amino Acid Changes with Vaccine Strains

## TL;DR

This study tracks how dengue virus type 2 evolved in French territories from 2000 to 2024, comparing it to current vaccines to assess potential impacts on vaccine efficacy.

## Contribution

The study provides a detailed genomic analysis of DENV2 evolution in French territories and identifies amino acid changes compared to Dengvaxia® and Qdenga® vaccines.

## Key findings

- DENV2 strains in French territories belong to Asian American and Cosmopolitan genotypes with distinct sublineages.
- Amino acid changes in prM/E regions differ between FTA strains and Dengvaxia® and Qdenga® vaccines.
- Some amino acid substitutions are shared across genotypes, potentially affecting vaccine efficacy.

## Abstract

Background: Dengue virus type 2 (DENV2) is endemic to hyperendemic in the French territories of the Americas (FTAs), including French Guiana, Guadeloupe, Martinique, Saint-Barthelemy, and Saint-Martin. In 2023–2024, French Guiana, Martinique, and Guadeloupe experienced unprecedented dengue epidemics partly associated with this serotype. In response, we conducted a retrospective study of the diversity of DENV2 strains circulating in the FTAs from 2000 to 2024. Methods: To this end, we selected DENV2 samples from the collection at the National Research Center for Arboviruses in French Guiana (NRCA-FG) and sequenced them using Oxford Nanopore Technologies (ONT)-based next-generation sequencing (NGS). Results: Phylogenetic analysis revealed that (i) the 77 DENV2 sequences from the FTAs belong to two distinct genotypes—Asian American and Cosmopolitan; (ii) from the 2000s up to the 2019 epidemic in French Guiana, all sequenced strains belonged to the Asian American genotype; (iii) and from 2019 to 2020, strains circulating in Martinique and Guadeloupe belonged to the Cosmopolitan genotype, specifically the Indian subcontinent sublineage, while (iv) strains from the 2023–2024 outbreak in Martinique, Guadeloupe, and French Guiana fall within a distinct sublineage of the same genotype—Other Cosmopolitan. Additionally, we analyzed amino acid (AA) changes in FTA sequences compared to the Dengvaxia® and Qdenga® vaccines. The analysis of amino acid changes in FTA sequences compared to the vaccines (Dengvaxia® and Qdenga®) identified 42 amino acid changes in the prM/E regions (15 in the prM region and 27 in the E region) relative to CYD-2 Dengvaxia® and 46 amino acid changes in the prM/E regions relative to Qdenga®, including 16 in the prM region and 30 in the E region. Some of these AA changes are shared across multiple genotypes and sublineages, with 8 substitutions in the prM region and 18 in the E region appearing in both analyses. This raises questions about the potential impact of these changes on vaccine efficacy. Conclusion: Overall, these findings provide a current overview of the genomic evolution of DENV2 in the FTA, which is crucial for developing more effective prevention and control strategies and for selecting future vaccines tailored to circulating strains.