Highly Effective mRNA-LNP Vaccine Against Respiratory Syncytial Virus (RSV) in Multiple Models

Area of Science:

• Virology
• Vaccinology
• Immunology

Background:

• Respiratory syncytial virus (RSV) pathogenesis involves the fusion (F) protein mediating viral entry.
• The prefusion (preF) form of the F protein is a key target for neutralizing antibodies and vaccine development.
• Antibodies targeting preF are crucial for effective RSV neutralization.

Purpose of the Study:

• To design and evaluate an mRNA vaccine (STR-V003) encoding the RSV preF protein.
• To assess the immunogenicity, protective efficacy, and safety of STR-V003 in animal models.
• To determine the potential of STR-V003 as a candidate for RSV prevention.

Main Methods:

• Development of STR-V003, an mRNA vaccine encapsulated in lipid nanoparticles (LNPs).
• Evaluation of immunogenicity, including neutralizing antibodies and preF-specific IgG, in mice and cotton rats.
• Assessment of protection efficacy by measuring viral loads in challenged animals.
• Toxicology studies, including repeated dose and local tolerance, in rats and non-human primates (NHPs).

Main Results:

• STR-V003 induced high levels of neutralizing and preF-specific IgG antibodies in mice and cotton rats.
• Significant reduction in RSV viral loads was observed in the lungs and nasal tissues of vaccinated animals.
• No significant enhancement of lung pathology or vaccine-enhanced disease (VED) was detected.
• Toxicology studies indicated a favorable safety profile for STR-V003.

Conclusions:

• STR-V003 demonstrates robust immunogenicity and protective efficacy against RSV challenge.
• The developed mRNA vaccine exhibits a favorable safety profile in preclinical animal models.
• STR-V003 represents a promising candidate for an effective RSV vaccine.