Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 119, Issue 14, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2119093119
Keywords
antiviral vaccines; spherical nucleic acids; rational vaccinology; infectious disease
Categories
Funding
- Northwestern University
- Air Force Office of Scientific Research Award [FA9550-17-10348]
- Polsky Urologic Cancer Institute of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University at Northwestern Memorial Hospital
- National Cancer Institute of NIH [R01CA208783, P50CA221747]
- Northwestern University's Cancer Nanotechnology Training Program - National Cancer Institute of NIH [T32CA186897]
- Edward Bachrach
- Dr. John N. Nicholson Fellowship
- University of Chicago Biological Sciences Division
- NCI Cancer Center Support Grant (CCSG) [P30 CA060553]
- NIH Office of Director [S10OD025194]
- Soft and Hybrid Nanotechnology Experimental Resource [NSF ECCS-2025633]
- State of Illinois
- International Institute for Nanotechnology
- [P41 GM108569]
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This study explores how the presentation of vaccine components in spherical nucleic acids (SNAs) can induce and maximize antiviral response. The SNA vaccine, encapsulating the receptor-binding domain (RBD) subunit and decorated with Toll-like receptor 9 agonist oligonucleotides, shows promising results in inducing immune responses in human cells and mice, outperforming traditional vaccines.
Despite recent efforts demonstrating that organization and presentation of vaccine components are just as important as composition in dictating vaccine efficacy, antiviral vaccines have long focused solely on the identification of the immunological target. Herein, we describe a study aimed at exploring how vaccine component presentation in the context of spherical nucleic acids (SNAs) can be used to elicit and maximize an antiviral response. Using COVID-19 as a topical example of an infectious disease with an urgent need for rapid vaccine development, we designed an antiviral SNA vaccine, encapsulating the receptor-binding domain (RBD) subunit into a liposome and decorating the core with a dense shell of CpG motif toll-like receptor 9 agonist oligonucleotides. This vaccine induces memory B cell formation in human cells, and in vivo administration into mice generates robust binding and neutralizing antibody titers. Moreover, the SNA vaccine outperforms multiple simple mixtures incorporating clinically employed adjuvants. Through modular changes to SNA structure, we uncover key relationships and proteomic insights between adjuvant and antigen ratios, concepts potentially translatable across vaccine platforms and disease models. Importantly, when humanized ACE2 transgenic mice were challenged in vivo against a lethal live virus, only mice that received the SNA vaccine had a 100% survival rate and lungs that were clear of virus by plaque analysis. This work underscores the potential for SNAs to be implemented as an easily adaptable and generalizable platform to fight infectious disease and demonstrates the importance of structure and presentation in the design of next-generation antiviral vaccines.
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