RESUMEN
Chirality is ubiquitous in biological systems, which is closely related to biological functions, life process, and even pathogenesis of diseases. However, the interface between the chirality of synthetic materials and organisms, particularly the immune system, remains poorly understood. Here, supramolecular chiral polymer micelles (SCPMs) are prepared by complexing antigenic proteins with chiral amino acid modified polyethyleneimine. The introduction of chirality not only reduces the toxicity of cationic polymer, but also benefits cell uptake and antigen presentation. Especially, D-chirality presents the lowest cytotoxicity, while promotes the highest expression level of costimulatory molecules on dendritic cells compared to L-chirality and achirality. The superiority of D-chirality to stimulate dendritic cell maturation is supported by immunization with D-SCPMs, which achieves significant antigen-specific proliferation of T cells in the spleen, lymph nodes and tumor of mice. Chirality-mediated antigen processing and presentation is demonstrated by D-SCPMs self-assembled from chiral alkaline histidine or neutral phenylalanine modified polyethyleneimine and tumor associated ovalbumin or severe acute respiratory syndrome coronavirus 2 spike 1 antigenic protein. Immunoactivation enabled by D-chirality opens a window to prepare potent nanotherapeutics for disease prevention and treatment. This article is protected by copyright. All rights reserved.
RESUMEN
New vaccine technologies are urgently needed to produce safe and effective vaccines in a more timely manner to prevent future infectious disease pandemics. Here, we describe erythrocyte-mediated systemic antiviral immunization, a versatile vaccination strategy that boosts antiviral immune responses by using erythrocytes decorated with virus-mimetic nanoparticles carrying a viral antigen and a Toll-like receptor (TLR) agonist. As a proof of concept, polydopamine nanoparticles were synthesized via a simple in situ polymerization in which the nanoparticles were conjugated with the SARS-CoV-2 spike protein S1 subunit and the TLR7/8 agonist R848. The resulting SARS-CoV-2 virus-mimetic nanoparticles were attached to erythrocytes via catechol groups on the nanoparticle. Erythrocytes naturally home to the spleen and interact with the immune system. Injection of the nanoparticle-decorated erythrocytes into mice resulted in greater maturation and activation of antigen-presenting cells, humoral and cellular immune responses in the spleen, production of S1-specific immunoglobulin G (IgG) antibodies, and systemic antiviral T cell responses than a control group treated with the nanoparticles alone, with no significant negative side effects. These results show that erythrocyte-mediated systemic antiviral immunization using viral antigen- and TLR agonist-presenting polydopamine nanoparticles-a generalizable method applicable to many viral infections-is effective new approach to developing vaccines against severe infectious diseases.