Spherical nucleic acids as an infectious disease vaccine platform

Abstract

Significance Using SARS-CoV-2 as a relevant case study for infectious disease, we investigate the structure–function relationships that dictate antiviral spherical nucleic acid (SNA) vaccine efficacy. We show that the SNA architecture can be rapidly employed to target COVID-19 through incorporation of the receptor-binding domain, and that the resulting vaccine potently activates human cells in vitro and mice in vivo. Furthermore, when challenged with a lethal viral infection, only mice treated with the SNA vaccine survived. Taken together, this work underscores the importance of rational vaccine design for infectious disease to yield vaccines that elicit more potent immune responses to effectively fight disease.

Rational Vaccinology: Harnessing Nanoscale Chemical Design for Cancer Immunotherapy

“…The physical arrangement of antigens within nanoscale vaccines (Figure , top right) strongly influences antigen delivery and overall vaccine immunogenicity and performance. For instance, a recently developed antiviral SNA encapsulating antigen [the receptor binding domain (RBD) of the full spike protein] against SARS-CoV-2 was found to robustly activate naı̈ve B cells in human peripheral blood mononuclear cells compared to the simple mixture due to the novel multivalent three-dimensional architecture of the SNA and the ability to optimally present both adjuvant and antigen . Another strategy involves presenting the antigen on the nanovaccine surface.…”

“…For instance, a recently developed antiviral SNA encapsulating antigen [the receptor binding domain (RBD) of the full spike protein] against SARS-CoV-2 was found to robustly activate naıve B cells in human peripheral blood mononuclear cells compared to the simple mixture due to the novel multivalent three-dimensional architecture of the SNA and the ability to optimally present both adjuvant and antigen. 101 Another strategy involves presenting the antigen on the nanovaccine surface. This structural arrangement has been found to be highly immunogenic because the multivalent display of peptide epitopes on a nanoparticle surface mimics the multivalent display of protein antigens on viral surfaces.…”

Applications of Functional DNA Materials in Immunomodulatory Therapy

“…SNAs can be efficiently taken up by a variety of cells, thereby effectively delivering drugs and probes to the interior of cells . Recently, Mirkin’s team developed a SARS-CoV-2 subunit vaccine using liposome-based SNAs which could effectively activate the antiviral immune response …”

“…In addition, functional DNA materials can also be used to develop SARS-CoV-2 vaccines. Recently, Teplensky et al designed a SARS-CoV-2 vaccine with spherical nucleic acid as adjuvant . They encapsulated RBD antigens in 80 nm liposome cores prepared from 1,2-dioleoyl- sn -glycero-3-phosphocholine (DOPC) and used CpG motifs as coats outside the liposome, while the authors further explored the optimal ratio between adjuvants and antigens.…”

“…107 Recently, Mirkin's team developed a SARS-CoV-2 subunit vaccine using liposome-based SNAs which could effectively activate the antiviral immune response. 108…”