Viromimetic STING Agonist-Loaded Hollow Polymeric Nanoparticles for Safe and Effective Vaccination against Middle East Respiratory Syndrome Coronavirus

Leon Chien Wei Lin, Chen Yu Huang, Bing Yu Yao, Jung Chen Lin, Anurodh Agrawal, Abdullah Algaissi, Bi Hung Peng, Yu Han Liu, Ping Han Huang, Rong Huay Juang, Yuan Chih Chang, Chien Te Tseng, Hui Wen Chen, Che Ming Jack Hu

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

The continued threat of emerging, highly lethal infectious pathogens such as Middle East respiratory syndrome coronavirus (MERS-CoV) calls for the development of novel vaccine technology that offers safe and effective prophylactic measures. Here, a novel nanoparticle vaccine is developed to deliver subunit viral antigens and STING agonists in a virus-like fashion. STING agonists are first encapsulated into capsid-like hollow polymeric nanoparticles, which show multiple favorable attributes, including a pH-responsive release profile, prominent local immune activation, and reduced systemic reactogenicity. Upon subsequent antigen conjugation, the nanoparticles carry morphological semblance to native virions and facilitate codelivery of antigens and STING agonists to draining lymph nodes and immune cells for immune potentiation. Nanoparticle vaccine effectiveness is supported by the elicitation of potent neutralization antibody and antigen-specific T cell responses in mice immunized with a MERS-CoV nanoparticle vaccine candidate. Using a MERS-CoV-permissive transgenic mouse model, it is shown that mice immunized with this nanoparticle-based MERS-CoV vaccine are protected against a lethal challenge of MERS-CoV without triggering undesirable eosinophilic immunopathology. Together, the biocompatible hollow nanoparticle described herein provides an excellent strategy for delivering both subunit vaccine candidates and novel adjuvants, enabling accelerated development of effective and safe vaccines against emerging viral pathogens.

Original languageEnglish (US)
Article number1807616
JournalAdvanced Functional Materials
Volume29
Issue number28
DOIs
StatePublished - Jul 11 2019

Keywords

  • Middle East respiratory syndrome coronavirus
  • STING
  • cdGMP adjuvant
  • hollow nanoparticle
  • virus mimicry

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics

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  • Cite this

    Lin, L. C. W., Huang, C. Y., Yao, B. Y., Lin, J. C., Agrawal, A., Algaissi, A., Peng, B. H., Liu, Y. H., Huang, P. H., Juang, R. H., Chang, Y. C., Tseng, C. T., Chen, H. W., & Hu, C. M. J. (2019). Viromimetic STING Agonist-Loaded Hollow Polymeric Nanoparticles for Safe and Effective Vaccination against Middle East Respiratory Syndrome Coronavirus. Advanced Functional Materials, 29(28), [1807616]. https://doi.org/10.1002/adfm.201807616