Tailoring biomaterials for vaccine delivery

Abstract

Biomaterials are substances that can be injected, implanted, or applied to the surface of tissues in biomedical applications and have the ability to interact with biological systems to initiate therapeutic responses. Biomaterial-based vaccine delivery systems possess robust packaging capabilities, enabling sustained and localized drug release at the target site. Throughout the vaccine delivery process, they can contribute to protecting, stabilizing, and guiding the immunogen while also serving as adjuvants to enhance vaccine efficacy. In this article, we provide a comprehensive review of the contributions of biomaterials to the advancement of vaccine development. We begin by categorizing biomaterial types and properties, detailing their reprocessing strategies, and exploring several common delivery systems, such as polymeric nanoparticles, lipid nanoparticles, hydrogels, and microneedles. Additionally, we investigated how the physicochemical properties and delivery routes of biomaterials influence immune responses. Notably, we delve into the design considerations of biomaterials as vaccine adjuvants, showcasing their application in vaccine development for cancer, acquired immunodeficiency syndrome, influenza, corona virus disease 2019 (COVID-19), tuberculosis, malaria, and hepatitis B. Throughout this review, we highlight successful instances where biomaterials have enhanced vaccine efficacy and discuss the limitations and future directions of biomaterials in vaccine delivery and immunotherapy. This review aims to offer researchers a comprehensive understanding of the application of biomaterials in vaccine development and stimulate further progress in related fields.

Keywords: Biomaterials; Drug delivery; Vaccine adjuvant; Vaccine delivery.

Fig. 1

Structure of some biological materials. A Self-assembling GPCs systems. Reproduced with permission from Ref. [47], Copyright 2024, Angewandte Chemie International Edition. B Schematic representation of liposome, liposome encapsulating hydrophobic and hydrophilic drugs, immunoliposome functionalized with targeting ligands, and sterically stabilized (“stealth”) liposome functionalized with inert polymers such as PEG. Reproduced with permission from Ref. [49], Copyright 2021, American Chemical Society Nano. C The immunostimulatory complex ISCOMATRIX was observed by electron microscopy after negative staining (Bar = 100 nm.) Reproduced with permission from Ref. [50], Copyright 1995, In Vaccine Design: The Subunit and Adjuvant Approach

Fig. 2

Vaccine delivery system. A Types of polymeric nanocarriers—nanosphere and nanocapsule—are depicted in the diagram. A polymeric shell that regulates the drug’s release profile from the core of the nanocapsule surrounds an oily core, typically where the medication dissolves. Using a continuous polymeric network as its foundation, nanospheres allow the medicine to either be maintained inside or adsorbed onto its surface. Reproduced with permission from Ref. [115], Copyright 2023, Technology in Cancer Research & Treatment. B Vesicle structure of nanoparticles based on liposomes. The polymer of the mashroom regime (low PEG density) consists of independent random coils of number Flory radius RF3 on the surface of the member. The polymer chain of the brush regime more mutually interacts and is densely packed. Reproduced with permission from Ref. [115], Copyright 2023, Technology in Cancer Research & Treatment

Fig. 3

Hydrogel. A Nanocarrier-hydrogel composites for vaccine delivery. Reproduced with permission from Ref. [119], Copyright 2019, Applied Materials Today. B Changes in the contact process of the inhalable bioadhesive hydrogel with the mucus surface. Dry SHIELD particles (grey spheres) are inhaled and they become swollen (blue spheres) once they are in contact with the mucus layer (pink layer). Finally, it forms a layer of hydrogel (blue layer) and adheres to the mucus layer. The process includes inhalation (i), swelling (ii) and adhesion (iii). The representative SEM image showing the morphology of SHIELD particles before swelling. The inset shows a zoomed-in view of one particle. Aerodynamic diameter of SHIELD particles. Data are mean ± s.d.; n = 4 independent experiments. Reproduced with permission from Ref. [143], Copyright 2023, Nature Materials

Fig. 4

Frozen microneedles. A Preparation of frozen microneedles. Reproduced with permission from Ref. [151], Copyright 2021, Nature Biomedical Engineering. B Evaluation of in vivo compatibility and safety of cryoMNs. (i) Assessment of skin recovery following application of frozen MN; (ii) Displaying skin H&E staining images at 30 min and 24 h post MN application, Scale bar, 200 μm; (iii) Showing images of skin stained with TUNEL (green) and Hoechst (blue) after MN application. Reproduced with permission from Ref. [151], Copyright 2021, Nature Biomedical Engineering

Fig. 5

Physicochemical properties of biomaterials affecting immune response. A The influence distribution of NP characteristics. (i) Spherical and larger NPs marginate more easily during circulation, whereas rod-shaped NPs extravasate more readily; (ii) Uncoated or positively charged NPs are cleared more quickly by macrophages. Reproduced with permission from Ref. [158], Copyright 2021, Nature Reviews Drug Discovery. B Pathway and fate of NP uptake. (i) endocytosis of NP: upon interaction with the cell surface, NPs—depending on their surface, size, shape and charge—are taken up by various types of endocytosis or pinocytosis via non-specific interactions, such as membrane wrapping, or specific interactions, such as with cell surface receptors; (ii) Ionizable NPs contribute to endosome escape: responsive NPs—such as ionizable NPs that become charged in low-pH environments-aid in endosomal escape and allow for intracellular delivery whereas unresponsive NPs often remain trapped and are destroyed by lysosome acidity and proteolytic enzymes [158]. C NP surface characteristic design for enhanced delivery. Reproduced with permission from Ref. [158], Copyright 2021, Nature Reviews Drug Discovery

Fig. 6

Inoculation by injection. A In order to investigate the local inflammatory response that occurred in skin and muscle following ID and IM administration routes, hematoxylin and eosin staining was conducted on days 1, 2, 3 and 7 after inoculation. Analysis of histological changes in skin tissue and muscle tissue at different time points following administration. Reproduced with permission from Ref. [169], Copyright 2023, International Journal of Molecular Sciences. B Investigation into the local retention and diffusion dynamics of the model antigen Cy7-OVA after injection into ICR mice via different routes. Reproduced with permission from Ref. [169], Copyright 2023, International Journal of Molecular Sciences

Fig. 7

Percutaneous immunization. A Composition and structure of MN. Reproduced with permission from Ref. [174], Copyright 2023, Small Science. B IPMN-G or IPMN-C facilitates transdermal delivery of gp100 and CCL21. Reproduced with permission from Ref. [174], Copyright 2023, Small Science. C Schematic of Anti-tumor mechanism of IPMN-GC in vivo. Reproduced with permission from Ref. [174], Copyright 2023, Small Science

Fig. 8

Intranasal administration. A IgA levels in serum and the quantity of IgA secreted in lavage solution were evaluated using ELISA. (i) The temporal changes of specific IgA in serum; (ii) Specific secretory IgA in small intestinal lavage fluid were analyzed. Reproduced with permission from Ref. [177], Copyright 2023, Frontiers in Immunology. B The proportion of germinal center (GC) B cells within nasal B cells was assessed using flow cytometry. Reproduced with permission from Ref. [178], Copyright 2023, Frontiers in Immunology. C Histological examination showed pathological changes in the lung tissue of the animals on days 3 and 7 post-attack. Reproduced with permission from Ref. [181], Copyright 2023, Scientific Reports

Fig. 9

Adjuvant enhances vaccine immunogenicity. A Vaccines without adjuvants induce modest production of T helper-polarizing cytokines, antibodies, and activated T cells. Reproduced with permission from Ref. [203], Copyright 2023, Signal Transduction and Targeted Therapy. B In contrast, vaccines with adjuvants promote the maturation of more APCs, increase the interaction between APCs and T cells, promote the production of greater numbers and more types of T helper-polarizing cytokines, multifunctional T cells, and antibodies, leading to broad and durable immunity, as well as dose and antigen savings. Reproduced with permission from Ref. [203], Copyright 2023, Signal Transduction and Targeted Therapy

Fig. 10

Action mechanism diagram of conveying system. A Extending the duration of antigen bioavailability. Reproduced with permission from Ref. [203], Copyright 2023, Signal Transduction and Targeted Therapy. B Targeting the APC antigen. Reproduced with permission from Ref. [203], Copyright 2023, Signal Transduction and Targeted Therapy. C Direct delivery of antigens to lymph nodes. Reproduced with permission from Ref. [203], Copyright 2023, Signal Transduction and Targeted Therapy. D Promoting cross-presentation of antigens. Reproduced with permission from Ref. [203], Copyright 2023, Signal Transduction and Targeted Therapy