Table 2.

Potential strategies to enhance therapeutic HPV DNA vaccine potency

Strategies	Approach	Reference
Strategies to increase the number of HPV antigen-expressing/HPV antigen-loaded DCs
[1] Routes of administration	(a) Intradermal administration via gene gun	[26, 27, 55]
	(b) Intramuscular injection followed by electroporation	[29–33]
	(c) Intradermal injection followed by laser treatment	[36, 37]
	(d) Intramuscular injection of DNA vaccine encapsulated by microparticles	[39, 40]
[2] Increasing intercellular spreading of HPV antigens to DCs	(a) VP22	[48–55]
	(b) MVP22	[56]
	(c) BVP22	[57, 58]
[3] Targeting Ag directly to DCs by linking Ag to DC-binding molecules	(a) Flt3 Ligand	[60, 61]
	(b) HSP70	[63]
[4] Enhancing the release of Ag into the DC milieu	(a) IM-coadministration of DNA encoding xenogenic MHC I with DNA vaccine increases cross-presentation in DCs	[67]
	(b) Enhanced release of HPV antigen from tumor cells pre-treated with chemo-radiotherapy	[69–74]
Improving HPV antigen expression, processing and presentation in dendritic cells
[1] Enhancing the level of antigen expression in transfected DCs	(a) Codon optimization	[32, 76–78]
	(b) Employing demethylating agents	[80, 81]
[2] Enhancing transcription of MHCI and MHC II	Co-administration of DNA encoding CIITA     with HPV DNA	[82]
[3] Enhancing antigen processing through MHC I pathway	(a) Targeting Ag for proteasomal degradation	[84, 85]
	(b) Targeting antigen to endoplasmic reticulum	[87–89]
	(c) Targeting antigen for cross-presentation	[90]
[4] Enhancing antigen processing through MHC II pathway	Linking HPV antigens to LAMP-1 to target     antigen to the endosomal/lysosomal compartment	[93, 94]
[5] Bypassing antigen processing by MHC I pathway	Linking HPV antigens to MHC I single chain     trimer to generate stable antigen presentation in     DC	[95]
Strategies to enhance DC function and interaction with T cells
[1] Prolonging DC and T cell survival to enhance T cell priming and activation	(a) Strategy to prolong DC survival	[96–98]
	(b) Strategy to prolong T cell survival	[99]
[2] Priming CD4+ T helper cells to enhance DC and T cell interaction		[100, 102]
[3] Employing cytokines and co-stimulatory signals to enhance T cell and DC activation		[25, 105]
[4] Promoting DC activation and expansion		[107–109, 111]
[5] Eliminating immunosuppressive Treg to improve T cell priming		[115–117]