Peptide Antigen Modifications Influence the On-Target and Off-Target Antibody Response for an Influenza Subunit...

Area of Science:

• Biomedical Nanotechnology
• Immunology
• Vaccine Development

Background:

• Peptide amphiphile micelles (PAMs) are advanced nanostructures with potential in drug delivery, enhancing cellular interactions and targeting.
• Modifications to peptides for micellization can alter their inherent bioactivity, impacting immune responses.
• Previous studies noted unusual murine antibody responses to PAMs with the M2 antigen, prompting further investigation.

Purpose of the Study:

• To investigate the immunogenicity of M2 antigen when incorporated into PAMs, comparing native protein linkages with non-native micellizing moieties.
• To assess the impact of PAM structure on antibody production, specifically focusing on on-target and off-target responses.

Main Methods:

• Synthesis of PAMs using an elongated M2 antigen (Palm2K-M21-24-(KE)4).
• Characterization of synthesized PAMs.
• Evaluation of PAM immunogenicity in bone marrow-derived dendritic cells and in vivo mouse models.

Main Results:

• The synthesized PAMs were immunogenic, eliciting antibody production.
• PAMs induced a significant level of off-target antibody production when compared to unmodified peptidyl micelles (PMs).

Conclusions:

• While the clinical significance of off-target antibodies from PAM vaccination requires further study, on-target antibodies from both PAM and PM vaccination recognized the M2 antigen in the context of the full M2 protein.
• This suggests that PAM-induced on-target antibodies may be capable of recognizing the influenza virus, offering potential for vaccine applications.