Preclinical evaluation of DENV1 mRNA vaccines in mice: Toward improved neutralizing antibody and T cell responses
2
Issued Date
2026-02-01
Resource Type
ISSN
07533322
eISSN
19506007
Scopus ID
2-s2.0-105028436427
Journal Title
Biomedicine and Pharmacotherapy
Volume
195
Rights Holder(s)
SCOPUS
Bibliographic Citation
Biomedicine and Pharmacotherapy Vol.195 (2026)
Suggested Citation
Khawsang C., Prompetchara E., Saithong S., Tharakhet K., Kaewpang P., Yostrerat N., Wangsoontorn P., Pitakpolrat P., Buranapraditkun S., Puttikhunt C., Lam K., Heyes J., Ketloy C., Weissman D., Ruxrungtham K. Preclinical evaluation of DENV1 mRNA vaccines in mice: Toward improved neutralizing antibody and T cell responses. Biomedicine and Pharmacotherapy Vol.195 (2026). doi:10.1016/j.biopha.2026.119037 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/114673
Title
Preclinical evaluation of DENV1 mRNA vaccines in mice: Toward improved neutralizing antibody and T cell responses
Corresponding Author(s)
Other Contributor(s)
Abstract
Dengue virus (DENV) infection represents a significant public health concern in tropical and subtropical areas, with increasing cases in parts of Europe. Currently, licensed vaccines, Dengvaxia® and Qdenga®, rely on live-attenuated platforms but show limited efficacy due to imbalanced immune responses and risks associated with antibody-dependent enhancement (ADE). In this study, we developed and evaluated nucleoside-modified mRNA vaccine encoding the dengue virus serotype 1 (DENV1) pre-membrane and envelope (prME) proteins. To reduce the potential for ADE, we incorporated the F108A mutation in the fusion loop, substituted the pr region with that from Japanese encephalitis virus (JEV), and incorporated a consensus envelope domain III (cEDIII) sequence to broaden neutralizing antibody responses. Immunogenicity was assessed in BALB/C mice immunized twice at three-week intervals with 1, 2.5, or 10 μg doses. The WT prME construct induced the highest DENV1 neutralizing antibody (NtAb) titers in a dose-dependent manner and robust T cell responses, particularly with the 2.5 μg dose. While the F108A and cEDIII modifications modulated antigen expression and broadened cross-reactivity, they also slightly reduced DENV-1-specific neutralizing titers. Among constructs, F108A+cEDIII demonstrated reduced ADE activity with improved cross-neutralization, especially against DENV3. However, the prJEV chimera exhibited low immunogenicity, likely due to prM-E domain incompatibility. Overall, the WT prME construct showed the most favorable balance of immunogenicity and safety, supporting its advancement as a prototype for future tetravalent dengue mRNA vaccine development.