Tetravalent dengue mRNA vaccination orchestrates balanced four-serotype immunity with durable memory and…

Abstract

An effective dengue vaccine must establish durable immunity across four dengue virus (DENV) serotypes, evade antibody-dependent enhancement (ADE), and overcome immune imprinting from prior exposure. Here, we developed TetprM-E mRNA-LNP, a tetravalent vaccine comprising LNP-formulated nucleoside-modified mRNAs encoding DENV1-4 precursor membrane-envelope (prM-E) antigens, and evaluated its immunogenicity, durability, protection and breath across serotype-specific immune backgrounds. Three immunization strategies elicited neutralizing titers greater than 1:1500 against each serotype. Passive transfer of immune sera conferred 100% survival and reduced viremia after lethal DENV2 challenge in immunocompromised mice. Vaccination induced DENV envelope (env)-specific CD8+T cells and CD4-dependent germinal-center responses. DENV env-binding antibodies persisted for 34 weeks alongside DENV env-specific memory B cells. Vaccine-elicited sera showed no measurable in vitro ADE. Although monovalent priming initially biased antibody responses, TetprM-E mRNA-LNP vaccination broadened neutralization across DENV1-4 regardless of priming serotype. Together, TetprM-E mRNA-LNP elicits broad, durable, and protective immunity despite serologic constraints from pre-existing immunity.

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BibTeX RIS

BibTeX

@misc{akther2026tetravalent,
  title = {{Tetravalent dengue mRNA vaccination orchestrates balanced four-serotype immunity with durable memory and protection in mice.}},
  author = {F. Akther and Y. R. Dalben and J. Villalpando and K. Levine and E. Buck and J. Polster and Z. Yin and H. Muramatsu and S. Tiwari and S. Sriram and C. B. Wilen and N. S. Joshi and R. P. McNamara and D. Weiskopf and L. V. Tse and N. Pardi and D. R. Martinez},
  howpublished = {bioRxiv},
  year = {2026},
  month = nov,
  doi = {10.64898/2026.11.09.765416},
  url = {https://www.biorxiv.org/content/10.64898/2026.11.09.765416v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - Tetravalent dengue mRNA vaccination orchestrates balanced four-serotype immunity with durable memory and protection in mice.
AU  - F. Akther
AU  - Y. R. Dalben
AU  - J. Villalpando
AU  - K. Levine
AU  - E. Buck
AU  - J. Polster
AU  - Z. Yin
AU  - H. Muramatsu
AU  - S. Tiwari
AU  - S. Sriram
AU  - C. B. Wilen
AU  - N. S. Joshi
AU  - R. P. McNamara
AU  - D. Weiskopf
AU  - L. V. Tse
AU  - N. Pardi
AU  - D. R. Martinez
PY  - 2026
DA  - 2026/11/09
PB  - bioRxiv
DO  - 10.64898/2026.11.09.765416
UR  - https://www.biorxiv.org/content/10.64898/2026.11.09.765416v1
AB  - An effective dengue vaccine must establish durable immunity across four dengue virus (DENV) serotypes, evade antibody-dependent enhancement (ADE), and overcome immune imprinting from prior exposure. Here, we developed TetprM-E mRNA-LNP, a tetravalent vaccine comprising LNP-formulated nucleoside-modified mRNAs encoding DENV1-4 precursor membrane-envelope (prM-E) antigens, and evaluated its immunogenicity, durability, protection and breath across serotype-specific immune backgrounds. Three immunization strategies elicited neutralizing titers greater than 1:1500 against each serotype. Passive transfer of immune sera conferred 100% survival and reduced viremia after lethal DENV2 challenge in immunocompromised mice. Vaccination induced DENV envelope (env)-specific CD8+T cells and CD4-dependent germinal-center responses. DENV env-binding antibodies persisted for 34 weeks alongside DENV env-specific memory B cells. Vaccine-elicited sera showed no measurable in vitro ADE. Although monovalent priming initially biased antibody responses, TetprM-E mRNA-LNP vaccination broadened neutralization across DENV1-4 regardless of priming serotype. Together, TetprM-E mRNA-LNP elicits broad, durable, and protective immunity despite serologic constraints from pre-existing immunity.
ER  -

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