Enhancing Antibody Responses by Multivalent Antigen Display on Thymus-independent DNA Origami Scaffolds

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Jan 30

PMID 38291019

Authors

Eike-Christian Wamhoff

Larance Ronsard

Jared Feldman

Grant A Knappe

Blake M Hauser

Anna Romanov

James Brett Case

Shilpa Sanapala

Evan C Lam

Kerri J St Denis

Julie Boucau

Amy K Barczak

Alejandro B Balazs

Michael S Diamond

Aaron G Schmidt

Daniel Lingwood

Mark Bathe

Affiliations

Soon will be listed here.

Abstract

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.

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