Peptide Antigen Modifications Influence the On-Target and Off-Target Antibody Response for an Influenza Subunit Vaccine
Background/Objectives: 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,...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
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| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/13/1/51 |
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| Summary: | Background/Objectives: 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<sub>2–16</sub> 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. Methods: PAMs were synthesized using an elongated M2 antigen (i.e., Palm<sub>2</sub>K-M2<sub>1–24</sub>-(KE)<sub>4</sub>). The PAMs were characterized, then their immunogenicity was evaluated with bone marrow-derived dendritic cells and in mice. Results: 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<sub>1–24</sub> peptide). Conclusions: 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. |
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| ISSN: | 2076-393X |