Mucosal Vaccination for Influenza Protection Enhanced by Catalytic Immune‐Adjuvant

Abstract

Influenza poses a severe threat to global health. Despite the whole inactivated virus (WIV)‐based nasal vaccine being a promising strategy for influenza protection, the mucosal barrier is still a bottleneck of the nasal vaccine. Here, a catalytic mucosal adjuvant strategy for an influenza WIV nasal vaccine based on chitosan (CS) functionalized iron oxide nanozyme (IONzyme) is developed. The results reveal that CS‐IONzyme increases antigen adhesion to nasal mucosa by 30‐fold compared to H1N1 WIV alone. Next, CS‐IONzyme facilitates H1N1 WIV to enhance CCL20‐driven submucosal dendritic cell (DC) recruitment and transepithelial dendrite(TED) formation for viral uptake via the toll‐like receptor(TLR) 2/4‐dependent pathway. Moreover, IONzyme with enhanced peroxidase (POD)‐like activity by CS modification catalyzes a reactive oxygen species (ROS)‐dependent DC maturation, which further enhances the migration of H1N1 WIV‐loaded DCs into the draining lymph nodes for antigen presentation. Finally, CS‐IONzyme‐based nasal vaccine triggers an 8.9‐fold increase of IgA‐mucosal adaptive immunity in mice, which provides a 100% protection against influenza, while only a 30% protection by H1N1 WIV alone. This work provides an antiviral alternative for designing nasal vaccines based on IONzyme to combat influenza infection.

Astaxanthin Protects Dendritic Cells from Lipopolysaccharide-Induced Immune Dysfunction

“…The chemotaxis of DCs was performed in a 24-well transwell chamber (pore size, 5 μm; Corning) as described previously [ 55 ]. DCs (1 × 10 5 cells) were then seeded onto the upper chambers and CCL19 (200 ng/mL) was added in the lower chamber.…”

A Live Attenuated H9N2 Avian Influenza Vaccine Prevents the Viral Reassortment by Exchanging the HA and NS1 Packaging Signals

“…Most of the live attenuated viruses can induce similar humoral immunity levels compared to inactivated viruses; however, it can effectively induce a stronger mucosal immunity and a broader and faster cellular immune response ( Hoft et al, 2011 ). Intranasal immunization is a great potential strategy based on its needle-free delivery, as well as production of mucosal antibodies at the site of entry for the influenza virus to neutralize and prevent transmission ( Qin et al, 2020 ). Compared with inactivated rTX, rTX-NS1-128 (mut) can remarkably increase the level of IL-6, suggesting that Th-2 immune response can be effectively stimulated.…”

Recent Progress on Biomaterials Fighting against Viruses

“…developed the iron oxide nanozyme based on chitosan, which promoted the antiviral alternative to combat influenza with an 8.9‐fold increase of IgA‐mucosal adaptive immunity in mice. [ 62 ] Zhang et al. described a virus‐mimetic nanovesicles with controlling size and functional polypeptides to adapt the design of vaccines against a wide array of viruses.…”

“…Besides, Qin et al developed the iron oxide nanozyme based on chitosan, which promoted the antiviral alternative to combat influenza with an 8.9-fold increase of IgAmucosal adaptive immunity in mice. [62] Zhang et al described a virus-mimetic nanovesicles with controlling size and functional polypeptides to adapt the design of vaccines against a wide array of viruses. [63] In an HIV vaccine, glycosylated HIV antigens presented in the forms of protein NPs have been shown to promote the antibody response to particulate antigens by concentrating in germinal centers [64] (Figure 10B).…”