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  2. Metalloparticle-Engineered Pickering Emulsion Displaying AAV-Vectored Vaccine for Enhancing Antigen Expression and Immunogenicity Against Pathogens

Metalloparticle-Engineered Pickering Emulsion Displaying AAV-Vectored Vaccine for Enhancing Antigen Expression and Immunogenicity Against Pathogens

  • Adv Mater. 2025 Jan 19:e2412627. doi: 10.1002/adma.202412627.
Zhaofei Guo 1 Fuhua Wu 1 2 Chenqi Guo 1 Rui Hu 1 Yangsen Ou 1 Yining Zhu 1 Shuang Luo 1 Yuanshuai Song 1 Penghui He 1 Chunting He 1 Yanhua Xu 1 Xue Tang 1 Ming Qin 1 Hairui Wang 1 Guangsheng Du 1 Xun Sun 1
Affiliations

Affiliations

  • 1 Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
  • 2 Sichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, China.
Abstract

Recombinant adeno-associated viruses (rAAVs) have emerged as promising vaccine vectors due to their enduring efficacy with a single dose. However, insufficient cellular immune responses and the random and non-specific distribution of AAVs post-injection may hinder the development of AAV vaccines. Here, a novel Pickering emulsion platform stabilized by biomineralized manganese nanoparticles and aluminum hydroxide, which can rapidly and efficiently load AAVs, is reported. This platform confers AAVs with favorable in vivo distribution kinetics, diversifying AAV endocytic pathways with reduced dependency on the sialic acid receptor-mediated route, and ultimately enhancing AAV Infection efficiency in antigen present cells (APCs). Concurrently, the Pickering emulsion substantially boosts endogenous 2'3'-cGAMP production, further activating the cGAS-STING pathway for stronger immune responses and improving protective efficacy in Bacterial infection models. The STING pathway activation also increases AAV target gene expression, potently augmenting the cross-protective potential of AAV vaccines for COVID-19. These synergistic effects ensure that effective immune responses are induced even at one-fifth of the AAV vaccination dose, while the Pickering emulsion further reduces the accumulation of AAV in the liver, thereby improving their safety. The findings highlight the potential of Pickering emulsions as valuable enhancers for viral vectors, providing insights for their broader clinical applicability.

Keywords

Adeno‐associated virus; Pickering emulsion; cGAS‐STING; vaccine.

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