Mucosal immunity elicited by a human-Fcγ receptor-I targeted intranasal vaccine platform enhances resistance against nasopharyngeal colonization of Streptococcus pneumoniae and induces broadly protective immunity against respiratory pathogens.

Summary

An adjuvant-free, hFcγRI-targeted intranasal vaccine induced stronger lung mucosal IgA/IgG and memory T cell responses than intramuscular dosing, enhancing resistance to Streptococcus pneumoniae nasopharyngeal colonization. Protection against influenza was comparable across routes, while intranasal delivery provided superior protection against lethal Francisella tularensis infection, highlighting pathogen-specific benefits of mucosal delivery.

Key Findings

• Intranasal hFcγRI-targeted PspA-FP elicited higher lung mucosal IgA/IgG and memory T cells than intramuscular administration, with similar systemic IgG.
• Intranasal vaccination improved resistance to Streptococcus pneumoniae nasopharyngeal colonization and outperformed intramuscular PspA-Alum.
• Protection against influenza was equivalent for intranasal and intramuscular routes, whereas intranasal delivery conferred superior protection against lethal Francisella tularensis infection.

Clinical Implications

If translated, intranasal FcγRI-targeted vaccines could improve prevention of nasal colonization and transmission (e.g., pneumococcus) and enhance protection against certain lethal respiratory infections without adjuvants.

Limitations

• Preclinical animal models; human FcγRI targeting may differ in human tissues
• Durability of mucosal responses and transmission effects were not fully characterized

Future Directions

Define durability and breadth of mucosal protection, assess transmission reduction, and initiate phase 1 safety/immunogenicity trials of intranasal FcγRI-targeted vaccines.