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

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.