Peptide-based vaccines: insights in a relationship between the explored administration routes and delivery systems

Peptide-based vaccine platforms always include the association of an immunoadjuvant with the antigen peptide and/or its incorporation into a specific delivery system. This strategy is necessary because, although this type of vaccine might induce immune responses with great potential for personalized immunotherapy and has low cost and ease of manufacture, peptides alone exhibit weak stability, suboptimal immunogenicity, and induce short-term immune responses. In this sense, the incorporation of the peptide antigen into a delivery system enables overcoming this issue, as these systems, in addition to enhancing immunogenicity by themselves, also protect the peptide from degradation. This review highlights how delivery systems tailored to specific administration routes significantly influence peptide-based vaccines' immune response and efficacy. A general overview demonstrated, for example, that for intramuscular administration, the most common one used in general vaccines, many studies use liposomal, polymeric or virus-based delivery systems for peptide delivery associated with respiratory diseases. Considering the subcutaneous route, many studies use nanostructures as vaccine delivery systems, and the antigen peptides most commonly associated with this route are cancer-related. The transdermal and intradermal platforms combine physical methods such as microneedles and iontophoresis with nanoparticles to promote a robust immune response, whereas the intranasal and oral administrations are frequently studied using polymeric systems, for respiratory and systemic diseases, respectively. Therefore, this review demonstrates that searching for a balance between safety and efficacy in using peptide-based vaccines is the greatest challenge, which can be positively impacted by exploring the versatility of delivery systems depending on the proposed administration route.