Boosting humoral and cellular immunity with enhanced STING activation by hierarchical mesoporous metal-organic framework adjuvants.

J Control Release

Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China; State Key Laboratory of Systems Medicine for Cancer, Institute for Personalized Medicine and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Published: June 2024

AI Article Synopsis

  • Vaccination is key to preventing infectious diseases and reducing death rates, but enhancing immune responses through safe adjuvants is still a challenge in vaccine development.!
  • Researchers created a new nanovaccine (R@M@HM801) that effectively co-delivers a STING agonist and a SARS-CoV-2 antigen using a specialized material, which helps boost immune responses.!
  • The study found that R@M@HM801 induced stronger immune responses (including T and B cell activation and higher antibody production) compared to traditional vaccines, showing its potential for improving vaccine effectiveness against viruses like Delta.

Article Abstract

Vaccination is essential for preventing and controlling infectious diseases, along with reducing mortality. Developing safe and versatile adjuvants to enhance humoral and cellular immune responses to vaccines remains a key challenge in vaccine development. Here, we designed hierarchical mesoporous MOF-801 (HM801) using a Cocamidopropyl betaine (CAPB) and a Pluronics F127 in an aqueous phase system. Meanwhile, we synthesized a novel SARS-CoV-2 nanovaccine (R@M@HM801) with a high loading capacity for both the STING agonist (MSA-2) and the Delta receptor binding domain (Delta-RBD) antigen. R@M@HM801 enhanced MSA-2 and RBD utilization and effectively co-delivered MSA-2 and RBD antigens to antigen-presenting cells in the draining lymph nodes, thereby promoting the activation of both T and B cells. Lymphocyte single-cell analysis showed that R@M@HM801 stimulated robust CD11bCD4 T cells, CXCR5CD4 T follicular helper (T), and durable CD4CD44CD62L, CD8CD44CD62L effector memory T cell (T) immune responses, and promoted the proliferative activation of CD26 B cells in vivo. Meanwhile, R@M@HM801 induced stronger specific antibodies and neutralization of pseudovirus against Delta compared to the RBD + MAS-2 and RBD + MAS-2 + Alum vaccines. Our study demonstrated the efficacy of a hierarchical mesoporous HM801 and its potential immune activation mechanism in enhancing adaptive immune responses against viruses and other diseases.

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Source
http://dx.doi.org/10.1016/j.jconrel.2024.05.010DOI Listing

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