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A bivalent mRNA vaccine against RSV infection in rodent models

Juan Liu1, Hanqing Zhao1, Wenhao Wang1

  • 1Nucleic Acid Medicine Innovation Center, Zhejiang Haichang Biotech Co., Ltd., Hangzhou, Zhejiang, China.

Frontiers in Immunology
|April 8, 2025
PubMed

Insights

New mRNA vaccines targeting Respiratory Syncytial Virus (RSV) fusion protein (F) show promise. These vaccines effectively generated strong immune responses and protected animals against RSV infection without causing adverse effects.

Area of Science:

  • Immunology
  • Vaccinology
  • Virology

Background:

  • Respiratory Syncytial Virus (RSV) poses a significant global health threat, particularly to infants and the elderly.
  • Current vaccine development often targets the RSV fusion (F) protein due to its conserved nature across strains, aiming for broad protection.
  • The prefusion conformation of the F protein (preF) is a key target for eliciting potent neutralizing antibodies.

Purpose of the Study:

  • To evaluate the immunogenicity and protective efficacy of novel chemically modified mRNA vaccines encoding a stabilized RSV prefusion F protein (preF).
  • To assess the safety profile of these mRNA vaccine candidates, specifically looking for Vaccine-Enhanced Respiratory Disease (VERD).
  • To determine the potential of these mRNA vaccines against both RSV A2 and B subtypes.

Main Methods:

  • Screening of two chemically modified mRNA vaccine candidates expressing stabilized RSV preF.
  • Immunization of mice and cotton rats followed by evaluation of humoral (antigen-specific binding and neutralizing antibodies) and cellular (T cell-mediated) immune responses.
  • Post-challenge assessment in cotton rats with live RSV A2 to evaluate vaccine protection (lung pathology, viral load) and safety (VERD).

Main Results:

  • The mRNA vaccine candidates successfully elicited robust antigen-specific binding and neutralizing antibody responses.
  • Vaccination induced Th1-biased T-cell responses in both mouse and cotton rat models.
  • Cotton rats vaccinated with the mRNA vaccine showed significantly reduced lung pathology and infectious viral loads after RSV challenge, with no observed VERD.

Conclusions:

  • The developed mRNA vaccines induce strong humoral and cellular immunity against RSV.
  • These mRNA vaccine candidates provide significant protection against RSV A2 and B subtypes in preclinical models.
  • The promising safety and efficacy data support further evaluation of these mRNA vaccines in human clinical trials.
Keywords:
RSV prefusion proteinimmunitymRNA vaccinesneutralizing antibodyprotection

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