Abstract
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.
| Original language | English (US) |
|---|---|
| Article number | e2119093119 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 119 |
| Issue number | 14 |
| DOIs | |
| State | Published - Apr 5 2022 |
Funding
ACKNOWLEDGMENTS. This work was supported by the following cores at Northwestern University: The Recombinant Protein Production Core, with special thanks to Dr. Sergii Pshenychnyi; the Proteomics Core Facility, with special thanks to Dr. Young Ah Goo; and the Integrated Molecular Structure Education and Research Center (IMSERC) Mass Spectrometry facility. Thanks go to Luise Hassler from the Division of Nephrology and Hypertension for arranging the figures for the lung histopathology presentation. This material is based upon work supported by the Air Force Office of Scientific Research Award FA9550-17-1-0348, the Polsky Urologic Cancer Institute of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University at Northwestern Memorial Hospital, and the National Cancer Institute of NIH under Awards R01CA208783 and P50CA221747. M.H.T. acknowledges support from Northwestern University\u2019s Cancer Nanotechnology Training Program supported by the National Cancer Institute of NIH Award T32CA186897. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. M.H.T. also acknowledges support from Edward Bachrach. M.E. was partially supported by the Dr. John N. Nicholson Fellowship. SARS-CoV-2 research at the Howard T. Ricketts Laboratory is supported by funds from the University of Chicago Biological Sciences Division. The Northwestern Proteomics Core Facility is supported by an NCI Cancer Center Support Grant (CCSG) P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center, Instrumentation Award S10OD025194 from NIH Office of Director, and the National Resource for Translational and Developmental Proteomics supported by Award P41 GM108569. The IMSERC MS facility at Northwestern University has received support from the Soft and Hybrid Nanotechnology Experimental Resource (Grant NSF ECCS-2025633), the State of Illinois, and the International Institute for Nanotechnology. This work was supported by the following cores at Northwestern University: The Recombinant Protein Production Core, with special thanks to Dr. Sergii Pshenychnyi; the Proteomics Core Facility, with special thanks to Dr. Young Ah Goo; and the Integrated Molecular Structure Education and Research Center (IMSERC) Mass Spectrometry facility. Thanks go to Luise Hassler from the Division of Nephrology and Hypertension for arranging the figures for the lung histopathology presentation. This material is based upon work supported by the Air Force Office of Scientific Research Award FA9550-17-1-0348, the Polsky Urologic Cancer Institute of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University at Northwestern Memorial Hospital, and the National Cancer Institute of NIH under Awards R01CA208783 and P50CA221747. M.H.T. acknowledges support from Northwestern University's Cancer Nanotechnology Training Program supported by the National Cancer Institute of NIH Award T32CA186897. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. M.H.T. also acknowledges support from Edward Bachrach. M.E. was partially supported by the Dr. John N. Nicholson Fellowship. SARS-CoV-2 research at the Howard T. Ricketts Laboratory is supported by funds from the University of Chicago Biological Sciences Division. The Northwestern Proteomics Core Facility is supported by an NCI Cancer Center Support Grant (CCSG) P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center, Instrumentation Award S10OD025194 from NIH Office of Director, and the National Resource for Translational and Developmental Proteomics supported by Award P41 GM108569. The IMSERC MS facility at Northwestern University has received support from the Soft and Hybrid Nanotechnology Experimental Resource (Grant NSF ECCS-2025633), the State of Illinois, and the International Institute for Nanotechnology.
Keywords
- antiviral vaccines
- infectious disease
- rational vaccinology
- spherical nucleic acids
ASJC Scopus subject areas
- General
