PLGA particle vaccination elicits resident memory CD8 T cells protecting from tumors and infection

The essential role of tissue-resident memory T cells (T_RM cells) in offering protection from recurring infections and malignant tumors is becoming increasingly clear. Due to their presence in many barrier tissues, T_RM cells are ideally located to rapidly respond to re-encountered pathogens. Moreover, a host of studies has shown that the quantity of T_RM cells correlates with increased survival rates in cancer patients. Therefore, vaccination strategies which induce a strong and sustained T_RM cell response are particularly promising. In this study we show that this response can be induced by employing a prime-boost vaccination strategy using biodegradable poly (D,L-lactide-co-glycolide) microspheres (PLGA MS). A subcutaneous prime immunization followed by an intranasal boost immunization led to a strong T_RM cell response in the lungs of mice 6 days after the boost vaccination. Although numbers subsequently declined, T_RM cells were still detectable 60 days after vaccination. Functionally, we observed that immunized mice were protected from lung metastasis formation and tumor growth in a B16Bl6 melanoma model. Furthermore, the T_RM cells induced by PLGA MS immunization provided protection in an infectious model using a recombinant influenza A virus (IAV). Taken together, these results show that the ability of PLGA MS to induce a strong T_RM cell response further supports their use as a potent vaccine.