An Adjustable Adjuvant STINGsome for Tailoring the Potent and Broad Immunity Against SARS-CoV-2 and Monkeypox Virus via STING and Necroptosis

The pandemics induced by emerging SARS-CoV-2 variants and monkeypox virus infection have triggered the urgent need for broad-spectrum vaccines. Except for "super" antigen designs, pattern recognition receptor (PRR) agonist-based adjuvants might blaze a new trail, through enhancing the immune response of conserved antigen epitopes shared among variants for cross-protection. Ideal adjuvants with proper adjustments could be conveniently applied to different antigens and antigen types in response to new pandemics. However, general strategies for modulating PRR agonist-based adjuvant properties to tailor the optimal immunity remain to be further explored. Here, an adjuvant platform STINGsome is described, composed of a STING agonist and pH-switchable IP9 liposomes, to simulate viral infection via STING activation and necroptosis. STINGsomes function as an efficient adjuvant to elicit broad and potent immune responses against multiple SARS-CoV-2 VOCs (Omicron BA.1, BA.2, BA.3, BA.4/5) and a monkeypox virus. More importantly, the adjuvant properties of STINGsomes can be tuned by simply adjusting the IP9 percentage, owing to distinct kinetics from local release to lymph node stimulation. Thus, this study provides a relatively simple strategy to adapt an adjuvant platform to different pathogenic antigens, ultimately achieving optimal protective responses. Viral infection triggers multiple host defense pathways such as STING and inflammatory cell death to generate inflammation. A biomimetic adjuvant STINGsome, composed of CDNs and IP9 liposomes, is constructed to simulate viral infection via STING activation and necroptosis. STINGsomes elicited broad and potent immune responses against SARS-CoV-2 Omicron subvariants and monkeypox virus, which can be tuned by adjusting IP9 percentage.image