DNA Origami Presenting the Receptor Binding Domain of SARS-CoV-2 Elicit Robust Protective Immune Response

Abstract

Effective and safe vaccines are invaluable tools in the arsenal to fight infectious diseases. The rapid spreading of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible of the coronavirus disease 2019 pandemic has highlighted the need to develop methods for rapid and efficient vaccine development. DNA origami nanoparticles (DNA-NPs) presenting multiple antigens in prescribed nanoscale patterns have recently emerged as a safe, efficient, and easily scalable alternative for rational design of vaccines. Here, we are leveraging the unique properties of these DNA-NPs and demonstrate that precisely patterning ten copies of a reconstituted trimer of the receptor binding domain (RBD) of SARS-CoV-2 along with CpG adjuvants on the DNA-NPs is able to elicit a robust protective immunity against SARS-CoV-2 in a mouse model. Our results demonstrate the potential of our DNA-NP-based approach for developing safe and effective nanovaccines against infectious diseases.

Innate Immune Stimulation Using 3D Wireframe DNA Origami

“…While nucleic acid nanodevices have been applied to various therapeutic areas, their immunostimulatory properties have been explored to a lesser degree. Such fundamental understanding of NANP immunological properties is important to inform the design of follow-on in vivo studies using CpG overhangs (e.g., Zeng et al, bioRxiv, and Oktay et al, bioRxiv), to further explore prophylactic and therapeutic potential of these nanomaterials. , By establishing a deeper understanding of the baseline immunostimulatory properties of unmodified wireframe NANPs and the relative impacts of various NANP design parameters on DNA nanoparticle-mediated tunable TLR9 activation, we can work toward enabling the design of DNA nanostructures with specific immunostimulatory profiles for targeted biological outcomes.…”

DNA nanostructures as biomolecular scaffolds for antigen display

“…The main role of adjuvants is to stimulate and boost the magnitude and persistence of immune responses (Pulendran et al, 2021). For instance, Oktay et al (2023) used DNA NP to present RBD antigens, along with multiple CpG 1018 adjuvants, which elicited a strong immune response with lower antigen quantities. Moreover, Matrix‐M exists in the form of NPs in vaccines (Bangaru et al, 2020), which also contributes to its adjuvant functions.…”

Functional nucleic acids as potent therapeutics against SARS-CoV-2 infection

“…As well as acting as a blocking module, the nucleic acid framework could also be functionalized as an antigen display platform to elicit robust protective immune response and improve the development of more efficient vaccines against fatal viruses. 55 , 56 , 57 , 58 Zhang et al. developed a DNA origami integrated with RBD binding aptamers to investigate the viral attachment and immune response initiated by the copy number and distribution pattern of SARS-CoV-2 RBDs ( Figure 7 D).…”