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Coming of age: mRNA vaccines for orthoflaviviruses

Fahima Akther1, Norbert Pardi2, David R Martinez3

  • 1Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.

Trends in Immunology
|November 6, 2025
PubMed

Insights

Messenger RNA (mRNA) vaccines, delivered via lipid nanoparticles (LNPs), represent a promising strategy for combating mosquito- and tick-borne orthoflaviviruses like dengue and Zika, offering rapid development and broad protection.

Area of Science:

  • Virology
  • Immunology
  • Vaccine Technology

Background:

  • Orthoflaviviruses (e.g., dengue, Zika, yellow fever) are significant public health threats transmitted by mosquitoes and ticks.
  • These viruses have pandemic potential, necessitating effective and rapidly deployable countermeasures.
  • Current vaccine strategies face challenges in achieving broad and durable protection against diverse orthoflaviviruses.

Purpose of the Study:

  • To review recent advancements in mRNA vaccine technology for orthoflaviviruses.
  • To examine innovations in antigen design and delivery platforms for improved vaccine efficacy.
  • To assess the potential for mRNA vaccines to provide broad, safe, and durable protection against orthoflavivirus infections.

Main Methods:

  • Review of recent scientific literature on mRNA vaccine development for orthoflaviviruses.
  • Analysis of innovations in lipid nanoparticle (LNP) delivery systems.
  • Evaluation of novel antigen design strategies for eliciting robust immune responses.

Main Results:

  • Lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccines offer a potent platform for delivering viral antigen-encoding mRNAs.
  • These synthetic vaccines simplify the expression of complex viral glycoproteins and allow for rapid, scalable manufacturing.
  • Innovations in antigen design and LNP delivery show promise for broadening vaccine protection against multiple orthoflaviviruses.

Conclusions:

  • mRNA vaccine technology presents a powerful and adaptable platform for developing vaccines against orthoflaviviruses.
  • Advancements in antigen design and LNP delivery are crucial for enhancing vaccine safety, durability, and breadth of protection.
  • This approach holds significant potential for mitigating the impact of orthoflavivirus epidemics and pandemics.
Keywords:
T cell immunityantigenmRNA vaccinesneutralizing antibodyorthoflaviviruses

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