Development of a Virus-Like Particle-Based Anti-HER2 Breast Cancer Vaccine

SIMPLE SUMMARY: Virus-like particles (VLPs) have attracted significant interest as immunotherapy platforms and cancer vaccines for inducing antigen-specific immune responses against tumors. We prepared a human epidermal growth factor receptor-2 (HER2) cancer vaccine, by conjugating the HER2-derived CH401 epitope to the external surface of Physalis mottle virus (PhMV)-like particles via copper-free click chemistry. Another candidate was prepared by loading Toll-like receptor 9 (TLR9) agonists as adjuvant into the interior cavity of PhMV-CH401—although the addition of the adjuvant conferred no additional immune priming. The VLP-based anti-HER2 vaccine candidate was administered subcutaneously, using a prime-boost immunization schedule and BALB/c mice. The vaccine candidate elicited a strong immune response, including high titers of HER2-specific immunoglobulins and increased the toxicity of antisera to DDHER2 tumor cells. DDHER2 tumor challenge studies demonstrated efficacy, as evident from the delayed onset of tumor growth and the prolonged survival of the vaccinated vs. naïve BALB/C mice. ABSTRACT: To develop a human epidermal growth factor receptor-2 (HER2)-specific cancer vaccine, using a plant virus-like particle (VLP) platform. Copper-free click chemistry and infusion encapsulation protocols were developed to prepare VLPs displaying the HER2-derived CH401 peptide epitope, with and without Toll-like receptor 9 (TLR9) agonists loaded into the interior cavity of the VLPs; Physalis mottle virus (PhMV)-based VLPs were used. After prime-boost immunization of BALB/c mice through subcutaneous administration of the vaccine candidates, sera were collected and analyzed by enzyme-linked immunosorbent assay (ELISA) for the CH401-specific antibodies; Th1 vs. Th2 bias was determined by antibody subtyping and splenocyte assay. Efficacy was assessed by tumor challenge using DDHER2 tumor cells. We successful developed two VLP-based anti-HER2 vaccine candidates—PhMV-CH401 vs. CpG-PhMV-CH401; however, the addition of the CpG adjuvant did not confer additional immune priming. Both VLP-based vaccine candidates elicited a strong immune response, including high titers of HER2-specific immunoglobulins and increased toxicity of antisera to DDHER2 tumor cells. DDHER2 tumor growth was delayed, leading to prolonged survival of the vaccinated vs. naïve BALB/C mice. The PhMV-based anti-HER2 vaccine PhMV-CH401, demonstrated efficacy as an anti-HER2 cancer vaccine. Our studies highlight that VLPs derived from PhMV are a promising platform to develop cancer vaccines.