Improving potency of Nanoliposomal AE36 peptide vaccine by adding CD4+ T cell helper epitope and MPL in TUBO breast cancer mice model

Abstract

Cancer peptide vaccines stimulate the immune system and activate efficient T cell responses towards cancerous cells. Despite this, the scant efficacy of peptide vaccines has led to modest clinical success in most instances. Hence, optimizing cancer peptide vaccines to enhance their effectiveness appeared to be critical to achieving successful treatment. Designing multiepitope peptide formulations using appropriate delivery systems is a promising strategy for increasing peptide vaccines' efficacy and triggering robust immune responses. Therefore, we studied a liposomal-based peptide vaccine composed of AE36 (HER2/neu-derived peptide) and PADRE (Pan HLA-DR peptide) as well as monophosphoryl lipid A (MPL) adjuvant. Then the prophylactic immune response was evaluated in BALB/c mice breast cancer models bearing TUBO tumors. We found that the liposomal form of AE36 peptide plus PADRE resulted in improved activation of CD4+ and CD8+ T cell responses and considerably increased production of IFN-γ. In addition, the presence of PADRE, as a CD4+ T helper epitope could enhance the potency of the liposomal AE36 peptide vaccine. Furthermore, this formulation resulted in a considerable reduction in tumor volume and increased survival in a murine model. Our findings suggest that a liposomal formulation containing the multiepitope peptides AE36, PADRE, and MPL could be a potential prophylactic vaccine candidate that triggers a robust antigen-specific immune response of CD8+ CTLs.