Single‐Shot Mesoporous Silica Rods Scaffold for Induction of Humoral Responses Against Small Antigens

Abstract

Vaccines have shown significant promise in eliciting protective and therapeutic responses. However, most effective vaccines require several booster shots, and it is challenging to generate responses against synthetic molecules and peptides often used to increase target specificity and improve vaccine stability. As continuous antigen uptake and processing by antigen‐presenting cells and persistent toll‐like receptor priming can amplify humoral immunity, it is explored whether a single injection of a mesoporous silica micro‐rod (MSR) vaccine containing synthetic molecules and peptides can generate potent and durable humoral immunity. A single injection of the vaccine targeting a gonadotropin‐releasing hormone (GnRH) decapeptide elicits high anti‐GnRH titer for over 12 months and generated higher titers than bolus or alum formulations. Targeting a Her2/neu peptide within the Trastuzumab binding domain causes immunoreactivity to Her2 on tumor cells and, MSR vaccines against nicotine generated long‐term anti‐nicotine antibodies. A single MSR injection induced germinal center (GC) activity for more than 3 weeks, generated memory B cells, and 7 days of immunostimulation by the vaccine is required to generate effective antibody responses. The MSR vaccine represents a promising technology to bypass the need for multiple immunizations and enhance long‐term antibody production in the context of reproductive biology, cancer, and chronic addiction.

Modulation of injectable hydrogel properties for slow co‐delivery of influenza subunit vaccine components enhance the potency of humoral immunity

“…All gel formulations displayed solid‐like properties and robust yield stresses as well as a large dependence of the viscosity on the shear rate. This high degree of shear‐thinning, coupled with rapid recover of the mechanical properties following shear, enable facile injectability 14,15 . These mechanical properties demonstrate that the PNP hydrogels yield under the high pressure delivered by syringe injections and flow smoothly through the needle into the subcutaneous space, where the materials rapidly reforms into a solid‐like depot for extended cargo delivery.…”

Designing spatial and temporal control of vaccine responses

“…These materials provide tools to direct the immune response by attracting endogenous cells to the vaccine site, increasing antigen uptake and providing activation cues locally and rapidly 135 . Various materials have been explored for the formation of a local inflammatory niche to enhance immune responses 136 ; however, the impact of specific niche properties (for example, specific innate cell populations and/or their activation profiles) and the duration of niche persistence on downstream vaccine responses are poorly understood. Studies with self-assembled scaffolds based on silica rods have indicated that the local inflammatory niche must persist for at least 7 days to achieve prolonged antibody titres, compared with a bolus control 136 .…”

“…Various materials have been explored for the formation of a local inflammatory niche to enhance immune responses 136 ; however, the impact of specific niche properties (for example, specific innate cell populations and/or their activation profiles) and the duration of niche persistence on downstream vaccine responses are poorly understood. Studies with self-assembled scaffolds based on silica rods have indicated that the local inflammatory niche must persist for at least 7 days to achieve prolonged antibody titres, compared with a bolus control 136 . By contrast, niches created by injectable hydrogels that persist for about 2–4 weeks lead to a more durable and higher-affinity humoral immune response than a bolus control 66 .…”

Biomaterial-based immunoengineering to fight COVID-19 and infectious diseases

“…72 Among various organic-or inorganic-based biomaterials, mesoporous silica-based vaccines represent a promising and versatile platform to present viral antigens, induce immune cell activation, and promote prolonged antibody production, as exemplified in the elegant work that highlights the development of mesoporous silica rod-based pore-forming platforms for in situ modulation of host immune cells as a vaccine against infectious diseases. 73 Soft biomaterials, including hydrogel scaffolds, can also offer a versatile platform to deliver a wide variety of therapeutics. High levels of biocompatibility, tunable physicochemical properties, controlled release, and tunable degradation profiles are among the promising characteristics of polymer-based hydrogels.…”