Turning the Old Adjuvant from Gel to Nanoparticles to Amplify CD8⁺ T Cell Responses

Due to its safety and efficacy, aluminum hydroxide is used as an immune adjuvant in human vaccines for over 80 years. Being a Th2 stimulator, the classical gel-like adjuvant, however, fails to generate CD8⁺ T cell responses, which are important for cancer vaccines. Here, aluminum hydroxide is turned from gel into nano-sized vaccine carriers AlO(OH)-polymer nanoparticles (APNs) to promote their lymphatic migration. After actively uptaken via scavenger receptor-A by antigen-presenting cells (APCs) resident in lymph nodes (LNs), APNs destabilize lysosomes resulting in efficient cytosolic delivery and cross-presentation of antigens. It is demonstrated that administration of APNs loaded with ovalbumin (OVA) and CpG led to the codelivery of both cargos into APCs in LNs, leading to their activation and subsequent adaptive immunity. A prime-boost strategy with low doses of OVA (1.5 µg) and CpG (0.45 µg) induces potent CD8⁺ T cell responses and dramatically prolongs the survival of B16-OVA tumor-bearing mice. More impressively, when using B16F10 lysates instead of OVA as antigen, substantial antitumor effects on B16F10 tumor model are observed by using APN-CpG. These results suggest the great potential of APNs as vaccine carriers that activate CD8⁺ T cell responses and the bright prospect of aluminum adjuvant in a nanoparticle formulation.