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

Author:

Wu Jun‐Jun1ORCID,Chen Guan‐Jie1,Fan Chen‐Yuan1,Shen Fan23,Yang Yi1,Pang Wei2,Zhao Zhen‐Nan1,Guan Hong‐Xin1,Wu Huan1,Lu Ying23,Fu Ya‐Juan1,Chen Qi1,Zheng Yong‐Tang2,Ouyang Songying1ORCID

Affiliation:

1. Key Laboratory of Microbial Pathogenesis and Interventions of Fujian Province University the Key Laboratory of Innate Immune Biology of Fujian Province Biomedical Research Center of South China Key Laboratory of OptoElectronic Science and Technology for Medicine of the Ministry of Education College of Life Sciences Fujian Normal University 350117 Fuzhou China

2. Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences Center for Biosafety Mega‐Science Kunming Institute of Zoology Chinese Academy of Sciences Kunming Yunnan 650223 China

3. University of Chinese Academy of Sciences 100049 Beijing China

Abstract

AbstractThe 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.

Funder

National Key Research and Development Program of China

National Natural Science Foundation of China

Natural Science Foundation of Fujian Province

Publisher

Wiley

Subject

Electrochemistry,Condensed Matter Physics,Biomaterials,Electronic, Optical and Magnetic Materials

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