DENV-2 Genetic Diversity and Variation in Antibody-Dependent Enhancement in Lao PDR
10 affiliations
- 1Department of Virology, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan
- 2Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan
- 3Program for Nurturing Global Leaders in Tropical and Emerging Communicable Diseases, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan
- 4National Center for Laboratory and Epidemiology, Ministry of Health, Vientiane 01002, Laos
- 5Department of Communicable Diseases Control, Ministry of Health, Vientiane 01002, Laos
- 6School of Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan
- 7Department of Tropical Viral Vaccine Development, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan
- 8Dejima Infectious Disease Research Alliance, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan
- 9Center for Vaccines Disease and Therapeutic Antibodies for Emerging Infectious Diseases, Shimane University, 1060 Nishikawatsucho, Matsue 690-8504, Japan
- 10Vietnam Research Station, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan
Abstract
All four dengue virus serotypes (DENV-1 to DENV-4) can cause severe and potentially fatal disease. Understanding the interplay between host immune responses and viral genetic diversity is particularly crucial in hyperendemic regions, where serotype shifts frequently occur during outbreaks. In this cross-sectional, surveillance-based study, we analyzed 350 patients with confirmed secondary dengue infection in Lao PDR, with samples collected between 2022 and 2023. Of these, 80 were successfully serotyped by RT-PCR and included in the serotype-specific analyses. Viral genotyping was performed using envelope (E) gene sequencing, and neutralizing antibody (nAb) titers and antibody-dependent enhancement (ADE) activities against all four DENV serotypes were assessed using single-round infectious particles in both FcγRIIA-negative and FcγRIIA-positive BHK-21 cells. The nAb titers were highest against DENV-2, followed by DENV-1, DENV-4, and DENV-3. Nevertheless, DENV-2 exhibited the highest ADE activity, suggesting that high nAb titers may not necessarily prevent ADE. We also documented the co-circulation of DENV-2 Cosmopolitan and Asian I genotypes. Our findings highlight the complex interplay between neutralizing and enhancing antibody responses during secondary infection, particularly in the context of DENV-2 infection. Our results emphasize the need to understand the dynamics of DENV transmission in hyperendemic settings and may inform future vaccine development and evaluation strategies.
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BibTeX
@article{xayavong2026denv2,
title = {{DENV-2 Genetic Diversity and Variation in Antibody-Dependent Enhancement in Lao PDR}},
author = {Dalouny Xayavong and Virasack Somoulay and Bouaphanh Khamphaphongphane and Phonepadith Xangxayarath and Hiromu Osako and Kei Yamasato and Motoki Ihara and Jean Claude Balingit and Mya Myat Ngwe Tun and Kouichi Morita and Arata Hidano and Futoshi Hasebe and Yuki Takamatsu},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27198869},
url = {https://www.mdpi.com/1422-0067/27/19/8869},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - DENV-2 Genetic Diversity and Variation in Antibody-Dependent Enhancement in Lao PDR
AU - Dalouny Xayavong
AU - Virasack Somoulay
AU - Bouaphanh Khamphaphongphane
AU - Phonepadith Xangxayarath
AU - Hiromu Osako
AU - Kei Yamasato
AU - Motoki Ihara
AU - Jean Claude Balingit
AU - Mya Myat Ngwe Tun
AU - Kouichi Morita
AU - Arata Hidano
AU - Futoshi Hasebe
AU - Yuki Takamatsu
PY - 2026
DA - 2026/10/05
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27198869
UR - https://www.mdpi.com/1422-0067/27/19/8869
AB - All four dengue virus serotypes (DENV-1 to DENV-4) can cause severe and potentially fatal disease. Understanding the interplay between host immune responses and viral genetic diversity is particularly crucial in hyperendemic regions, where serotype shifts frequently occur during outbreaks. In this cross-sectional, surveillance-based study, we analyzed 350 patients with confirmed secondary dengue infection in Lao PDR, with samples collected between 2022 and 2023. Of these, 80 were successfully serotyped by RT-PCR and included in the serotype-specific analyses. Viral genotyping was performed using envelope (E) gene sequencing, and neutralizing antibody (nAb) titers and antibody-dependent enhancement (ADE) activities against all four DENV serotypes were assessed using single-round infectious particles in both FcγRIIA-negative and FcγRIIA-positive BHK-21 cells. The nAb titers were highest against DENV-2, followed by DENV-1, DENV-4, and DENV-3. Nevertheless, DENV-2 exhibited the highest ADE activity, suggesting that high nAb titers may not necessarily prevent ADE. We also documented the co-circulation of DENV-2 Cosmopolitan and Asian I genotypes. Our findings highlight the complex interplay between neutralizing and enhancing antibody responses during secondary infection, particularly in the context of DENV-2 infection. Our results emphasize the need to understand the dynamics of DENV transmission in hyperendemic settings and may inform future vaccine development and evaluation strategies.
SN - 1422-0067
ER -