Intranasal DNA nanocarrier vaccines with surface-patterned antigens enhance efficacy against respiratory syncytial virus.

Summary

A rationally engineered library of DNA nanocarriers displaying patterned RSV pre-F antigens achieved strong and durable systemic and mucosal immunity in mice, matching or surpassing approved trimeric mRNA vaccines in durability. Intranasal delivery outperformed intramuscular mRNA in eliciting respiratory mucosal immunity and conferred robust protection against RSV challenge.

Key Findings

• Engineered DNA nanocarriers organized pre-F monomer antigens into optimized surface patterns to maximize B cell activation.
• Intranasal vaccination induced humoral responses in mice comparable to an approved trimeric mRNA RSV vaccine, with greater durability.
• Intranasal DNA nanovaccine elicited robust respiratory mucosal immunity and provided strong protection against RSV challenge, unlike intramuscular mRNA vaccination.

Clinical Implications

If translated to humans, intranasal DNA nanocarrier vaccines could complement or replace systemic RSV vaccines by providing durable mucosal protection, potentially reducing transmission and severe disease.

Limitations

• Preclinical mouse study; human immunogenicity, safety, and manufacturability remain unproven.
• Long-term durability and breadth across RSV strains and human mucosal compartments are unknown.

Future Directions

Advance to GLP toxicology and phase 1 trials assessing mucosal and systemic immunity, durability, and shedding/transmission endpoints; extend patterning principles to influenza, SARS-CoV-2, and pan-viral antigens.