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

Peptide amphiphile micelles (PAMs) are an exciting nanotechnology currently being studied for a variety of biomedical applications, especially for drug delivery. Specifically, PAMs can enhance in vivo trafficking, cell-targeting, and cell interactions/internalization. However, modifying peptides, as is commonly performed to induce micellization, can influence their bioactivity. In our previous work, murine antibody responses to PAMs containing the influenza antigen M2_2-16 were slightly incongruous with prior PAM vaccine studies using other antigens. In this current work, the effect of native protein linkages and non-native micellizing moieties on M2 immunogenicity was studied.

PAMs were synthesized using an elongated M2 antigen (i.e., Palm₂K-M2_1-24-(KE)₄). The PAMs were characterized, then their immunogenicity was evaluated with bone marrow-derived dendritic cells and in mice.

Although the modification scheme yielded immunogenic PAMs, these PAMs induced a substantial amount of off-target antibody production compared to unmodified peptidyl micelles (PMs, M2_1-24 peptide).

While the impact PAM-induced off-target antibodies had on vaccine efficacy remains to be elucidated, on-target antibodies from both PAM- and PM-vaccinated mice were excitingly able to recognize the M2 antigen within the context of the full M2 protein. This provides preliminary evidence that the PAM-induced on-target antibodies will at minimum be able to recognize the influenza virus upon exposure.