Table 3. DC targeted nanoparticle-based vaccines.

Vector	Antigen (Ag)	Target	Targeting moiety	Key Findings	Ref.
Animal in vitro and in vivo
Polymer Particles	Model Ag:
	• OVA	DEC205	Monoclonal Ab	100 fold less adjuvant required, as compared to soluble forms. Reduced serum cytokine storm and related toxicity	[90]
		DC-SIGN	PMAM dendrimers	Robust CD4+ & CD8+ T cell responses when loaded to BMDCs derived from DC-SIGN-transgenic mice	[129]
		Mannose R	Mannan	Enhanced CD4+ and CD8+ T cell responses in vitro and in vivo	[89]
			Mannosylated-alginate	Targeted nanogel delivery induced more efficient Th1 response in vitro	[130]
Liposomes	Model Ag:
	• OVA	DEC205	Monoclonal Ab	Strong Ag-specific CTL response in splenic T cells and marked protection against tumor growth. LPS or IFN-y used as adjuvant.	[131]
		DC-SIGN	Glycans	Only glycan-modified non-PEGylated liposomes could bind to DC-SIGN	[132]
		Mannose R	Glycan ligands	Enhanced cross-presentation and Th1 skewing. Found to be independent of TLR-mediated signaling	[133]
		TLR5	Flagellin-related peptides	Induced DC maturation and Ag-specific CD8 & humoral immunity, which significantly inhibited tumor growth/metastasis &induced complete tumor regression in majority of mice tumor models	[134]
	Infectious Ag:
	• HIV gp120 18IIIB	Mannose R	Oligomannose – neoglycolipid	These coated liposomes were proposed as adjuvants. Induced CD8+ CTL response.	[135]
	• Neisseria PorA	Mannose R	Ligands	On subcutaneous immunization, Increased localization in draining lymph nodes and improved bactericidal Ab response	[136]
	Tumor Ag:
	• ErbB2 p63-71	Mannose R	Mannosylated ligands	Mannose-targeted liposomes had higher anti-tumor therapeutic efficiency allowing use of lesser quantities of both TLR ligands & peptide epitopes. TLR2/6 agonists found to be more efficient than TLR1/2 agonist for tumor eradication	[91]
	• HPV16 E7	Mannose R	Mannan	Coating of DOTAP liposomes with mannan significantly enhanced both preventive & therapeutic anti-tumor effects in vivo	[137]
Viruses /Virus-likeparticles	Model Ag:
	• OVA	DC-SIGN	Engineered Sindbis viral glycoprotein	Specific transduction and maturation of DCs by lentivector. Generated Ag-specific CD8+T cells and significant Ab response. Protected against tumor growth and induced regression of established tumors	[138]
	Tumor Ag:
	• TRP2180-188	CD40	CD40L extracellular domain	Targeted adenovector enhanced both transduction & maturation of DCs. Improved CD8+ T cell immunity and therapeutic efficacy in a melanoma model	[139]
Human in vitro
Polymer Particles	Model Ag:
	• TT	DC-SIGN	Monoclonal Ab	Nanoparticles, but not microparticles improved antigen presentation. No adjuvant used	[88]
	Tumor Ag:
	• gp100	DC-SIGN	Monoclonal Ab / carbohydrate ligands	Targeting antigens and adjuvants within the same particles enhanced CD8+ T cell stimulation potential. Receptor-specific antibodies more effective than carbohydrates	[90,92]
		Clec9A	Monoclonal Ab	Cross-presented by BDCA3+ DCs. Adjuvants R848 & poly IC	[93]
		DEC205, DCIR, BDCA2, FcR CD32	Monoclonal Ab	Delivered to plasmacytoid dendritic cells. Adjuvant R848. Triggered robust Type I IFN response	[94]
Liposomes	Tumor Ag:
	• NY-ESO-1	Fcy-R	Fc fragment from IgG	Co-encapsulated with adjuvants Palm-IL-1 & MAP-IFN-y, generated potent immunological responses	[140]
	•LHRH	Fcy-R	Fc fragment from IgG	Enhanced immune response compared to non-targeted NP & soluble peptides	[141]
Viruses /Virus-like particles	Infectious Ag:
	• Haem-influenza M1	CD40	Monoclonal Ab Fv fragment	Superior ability to activate antigen-specific cytotoxic T lymphocyte response, compared to non-targeted adenoviral vectors	[142]

^*Fcy= constant fragment of IgG, Fv= variable fragment.