Self-Adjuvant Effect by Manipulating the Bionano Interface of Liposome-Based Nanovaccines

Abstract

Nanovaccines are of increasing scrutiny due to their plasticity in size, composition, and surface properties to enhance antigenicity. However, inevitable absorption of plasma proteins affects the in vivo fate of nanovaccines by reshaping biological identity. Herein IgM was validated as a self-adjuvant by regulating antigen-presenting cells recognition of liposome-based nanovaccines. DCDX-modified liposomes with loading of ovalbumin (DCDX-sLip/OVA) heavily absorbed IgM via electrostatic interaction, demonstrating significant splenic B cells targeting. IgM absorbed on DCDX-sLip/OVA enhanced antigen uptake and presentation by both IgM-complement and IgM-FcμR pathways. DCDX-sLip/OVA induced a stronger IgG1 titer than ovalbumin-loaded plain liposomes (sLip/OVA) while maintaining a comparably high level of IgG2a titer with high biosafety, indicating that IgM absorption after DCDX modification could improve the antigenicity by enhancing the Th2-polarized immune response. The present work suggested manipulation of IgM absorption may provide a new impetus to improve in vivo performance of nanovaccines.

Folic Acid Enables Targeting Delivery of Lipodiscs by Circumventing IgM-Mediated Opsonization

“…The in vivo process of targeted delivery systems is extremely complicated. , The formation of protein corona, which alters the synthetic identity to biological one and severely affects in vivo performance of nanocarriers (e.g., targeting ability, pharmacokinetics, immunogenicity), has received increasing attention. − We recently found that natural IgM in blood avidly absorbed on the surface of FA-functionalized liposomes (FA-sLip) to hinder receptor recognition, rapidly activating complement and accelerating blood clearance of liposomes. − Evading IgM absorption-mediated complement activation and downstream cascade is a key point for improving the in vivo performance and achieving FA-enabled targeting.…”

“…However, nearly all FA-enabled targeted therapeutics in clinical trials ended in failure. The delivery process of nanocarriers in vivo is complicated, and the formation of protein coronas is now attracting increasing attention. − Natural IgM is a highly effective opsonin to trigger classic complement activation after absorption on the particle surface, severely affecting the in vivo performance of nanocarriers. , We recently found that natural IgM in blood avidly absorbed on the surface of FA-functionalized liposomes to impair the delivery efficiency. − Evading IgM absorption-mediated complement activation is a key point to improve the in vivo performance.…”

Nanovaccines against Animal Pathogens: The Latest Findings

“…IgM (after spontaneous absorption on the nanosurface) serve as self-adjuvant by regulating antigen-presenting cell recognition and complement activation [106] Carriers consisting of non-encoding RNA complexed with protamine (a cationic protein activating TLR7) naked 1-methylpseudouridine modified mRNA to small-molecule TLR2 and TLR7 agonists [107] Lipid-PLGA nanoparticles Hyaluronic acid (HA)-decorated cationic lipid-poly(lactide-co-glycolide) acid (PLGA) hybrid nanoparticles (HA-DOTAP-PLGA NPs) [108] Nanoemulsions A self-assembled biocompatible cationic-covered with hyper-branched poly(ethyleneimine) nanoemulsion has superior adjuvant activity than the non-cationic and traditional adjuvants in vivo.…”

Facile Separation of PEGylated Liposomes Enabled by Anti-PEG scFv

“…Liposome has been widely used for drug delivery in the medical field, for its good biocompatibility, low toxicity, and high loading capacity. − The introduction of polyethylene glycol (PEG) to liposome extended circulation in blood. PEG forms a brush-like protective layer on the surface to sterically stabilize liposome and to reduce recognition by opsonins and then is subsequent cleared by the mononuclear phagocyte system (MPS). , PEGylated liposomes have been developed such as Doxil, an early approved anticancer nanomedicine by FDA in 1995, with doxorubicin (DOX) encapsulated in the aqueous core of a liposome and used in advanced ovarian cancer, multiple bone marrow cancer, and Kaposi’s sarcoma complicated by HIV .…”