Journal Article

Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds

Balazs, Alejandro B., Feldman, Jared, Lam, Evan C., Diamond, Michael S., Lingwood, Daniel, Romanov, Anna, Bathe, Mark, Hauser, Blake M., Knappe, Grant A., Schmidt, Aaron G., Barczak, Amy K., Boucau, Julie, Wamhoff, Eike-Christian, Sanapala, Shilpa, Denis, Kerri J. St, Case, James Brett, Ronsard, Larance

2024

Overview

Protein-based virus-like particles (P-VLPs) are commonly used to spatially organize antigens and enhance humoral immunity through multivalent antigen display. However, P-VLPs are thymus-dependent antigens that are themselves immunogenic and can induce B cell responses that may neutralize the platform. Here, we investigate thymus-independent DNA origami as an alternative material for multivalent antigen display using the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, the primary target of neutralizing antibody responses. Sequential immunization of mice with DNA-based VLPs (DNA-VLPs) elicits protective neutralizing antibodies to SARS-CoV-2 in a manner that depends on the valency of the antigen displayed and on T cell help. Importantly, the immune sera do not contain boosted, class-switched antibodies against the DNA scaffold, in contrast to P-VLPs that elicit strong B cell memory against both the target antigen and the scaffold. Thus, DNA-VLPs enhance target antigen immunogenicity without generating scaffold-directed immunity and thereby offer an important alternative material for particulate vaccine design. Three-dimensional DNA origami constructs can be used to deliver vaccine antigens in a multi-valent form. Here the authors design a DNA origami system for SARS-CoV-2 proteins and characterize in mice the immune response and protective capacity of generated antibodies, finding that the construct itself is not immunogenic.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/1 / 13/106 / 13/31 / 14/34 / 14/35 / 147/143 / 631/250/2152/1566/1571 / 631/250/2152/2153/1291 / 631/250/254 / 631/250/590 / 639/925/926/1050 / 64/110 / 64/60 / 82/29 / 82/80 / 82/83 / Antibodies / Antigens / Antisera / COVID-19 / Deoxyribonucleic acid / DNA / DNA vaccines / DNA viruses / Humanities and Social Sciences / Humoral immunity / Immune response / Immune system / Immunity / Immunization / Immunogenicity / Immunological memory / Lymphocytes / Lymphocytes T / multidisciplinary / Neutralizing / Proteins / Scaffolds / Science / Science (multidisciplinary) / Severe acute respiratory syndrome coronavirus 2 / Spike protein / Thymus / Thymus gland / Vaccines / Valency / Virus-like particles