3). FcRider functions as a multivalent immunogen displayer and stimulates antigen-specific B cells without any exogenous adjuvant. As an antibody derivative, afucosylated FcRider could be a novel platform combining vaccines and therapeutic antibodies, integrating active and passive immunizations into single-modality hybrid immunization to provide complete and long-lasting protection against infections, and may open new avenues in cancer immunotherapy as well. Keywords:adjuvant, vaccine, Fc, afucosylation, nanoparticle Statement of Significance: Active ABT-239 immunization (vaccination) and passive immunization (transfer of neutralizing antibodies) are both crucial for protection against pathogens, yet administered in mutually unique ways due to lack of compatible adjuvants. We glyco-engineered recombinant Fc nanoparticles, FcRider, with endogenous adjuvant activities ABT-239 and enhanced Fc-mediated effector functions to materialize the concept of hybrid immunization. == Introduction == In immunology, an adjuvant is a substance that increases or modulates the immune response to a vaccine. Currently, only a few adjuvants other than aluminum salts (alum) have been licensed as components of vaccines in the USA. These are 4-monophosphoryl lipid A (MPL), CpG oligonucleotides, MPL and QS-21 mixed in a liposomal formulation, and the oil-in-water emulsion MF59 [1]. While more are being developed in the research pipelines, these adjuvants have mechanisms of action ABT-239 (MOAs) that are either not well defined or mainly centered on various Toll-like receptor (TLR) pathways [2]. All these adjuvants/formulations are intended for intramuscular (i.m.) or subcutaneous (s.c.) injection, as they are often hydrophobic or oil-based, and show toxic side effects or could cause systemic inflammation and cytokine overproduction when applied directly through intravenous (i.v.) or mucosal routes. These side effects, although taken for granted, actually limited our imagination in that immunization, the most genius way of humankind to fight infections, is forced to fall into two mutually unique camps: passive immunization (adoptive transfer of protective antibodies) and active immunization (vaccination). Oftentimes, in order to provide immediate protection, blocking or neutralizing antibodies are injected intravenously in formulated solutions without any adjuvant. For instance, the SARS-CoV-2-neutralizing antibodies REGN-COV2 and Sotrovimab are administered by intravenous infusion. On the other hand, vaccines are co-administered with adjuvants intramuscularly or subcutaneously with a delay in weeks or months for the appearance of induced highly potent antibodies and cellular responses. Can energetic and passive immunizations become mixed in one suitable setting, i.e. providing i.v. or i.m. shot of neutralizing antibodies while at the same time vaccinating the sponsor, to supply even more long-lasting and complete protection? For the very first time, we propose the word hybrid immunization to spell it out this setting of immunization. To probe for such Itgb1 a chance, we centered on developing book adjuvants that enable co-administration of vaccines and restorative antibodies in one modality. Just like TLRs indicated on different antigen-presenting cells (APCs), activating Fc gamma receptors (FcRs) will also be indicated on APCs, including monocytes/macrophages, granulocytes, dendritic cells, and follicular dendritic cells (FDCs) [3]. While TLR agonists are becoming exploited as adjuvants [1,4], very little attention is attracted on interesting FcRs for adjuvanticity. One main obstacle is the fact that such FcR-engagers need to effectively contend with endogenous IgG in huge molar extra in blood flow or tissue, that is at about 10 mg/ml amounts [5] normally. We hypothesize that when creating a recombinant Ag-Fc fusion and using afucosylation technology to improve the binding of IgG Fc with activating FcRs (human being FcRIIIA and mouse FcRIV) [6], possibly the Fc:FcR discussion could transmit solid stimulatory signals to market immunogen catch and demonstration by APCs and features as an intrinsic adjuvant. Alternatively, it is popular that Fc afucosylation enhances the effector features of restorative antibodies by 50100 collapse [7], as well as the dosages for theirin vivoadministration could possibly be decreased considerably, to be able to combine therapeutic vaccines and antibodies in one entity. Out of the reasoning, we manufactured an afucosylated (AF) two-unit tandem hIgG1 Fc became a member of from the trimerization series Foldon [8]. The murine version is arranged like a two-unit tandem mIgG2a Fc joined by Foldon similarly. We name these as FcRider. Herein, we.