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Production of E. coli-expressed Self-Assembling Protein Nanoparticles for Vaccines Requiring Trimeric Epitope Presentation

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mRNA-LNP Vaccines Encoding for Dengue Optimized prM/ENV Proteins Induce Protective Immunity without ADE.

Enzo LaMontia-Hankin¹, Clayton J Wollner¹, E Taylor Stone²

¹Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, Illinois, USA.

Biorxiv : the Preprint Server for Biology

|December 3, 2025

Summary

This summary is machine-generated.

A new tetravalent Dengue virus (DENV) vaccine using mRNA-LNP technology was developed. This vaccine protects against all four DENV serotypes and reduces the risk of antibody-dependent enhancement (ADE).

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Published on: November 1, 2011

Area of Science:

Virology
Immunology
Vaccine Development

Background:

Dengue virus (DENV) causes ~400 million infections yearly, with no approved vaccines for naive individuals.
Four DENV serotypes (DENV 1-4) exist, complicating vaccine development due to potential antibody-dependent enhancement (ADE).
Previous work showed a DENV-1 mRNA vaccine lacking the fusion loop (FL) protected against DENV and avoided ADE.

Purpose of the Study:

To develop and evaluate mRNA-LNP vaccines for DENV serotypes 2, 3, and 4.
To create a tetravalent vaccine combining monotypic DENV vaccines.
To assess the immunogenicity, protective efficacy, and ADE potential of the tetravalent vaccine.

Main Methods:

Designed mRNA-LNP vaccines encoding prM-E proteins for DENV 2, 3, and 4, incorporating ΔFL modifications and chimeric E proteins.
Assessed vaccine immunogenicity and protection against lethal homotypic DENV challenge in mice.
Formulated monotypic vaccines into a tetravalent vaccine and evaluated its performance in mice.

Main Results:

Monovalent mRNA-LNP vaccines for DENV 2, 3, and 4 elicited serotype-specific neutralizing antibodies and protected against lethal homotypic challenge.
Fusion loop mutation reduced ADE in vaccinated mouse sera.
The tetravalent vaccine induced neutralizing responses against all DENV serotypes and provided protection against lethal challenges.

Conclusions:

Monovalent DENV mRNA-LNP vaccines generate protective immunity and mitigate ADE risk.
A first-generation ADE-altered tetravalent DENV vaccine has been developed.
This approach offers a promising strategy for a safe and effective pan-Dengue vaccine.