Table 1.

Characteristics of current therapeutic HPV vaccines

	Advantages	Disadvantages	Reference
Bacterial vector based	Highly immunogenic Wide range of selection for available vectors Can deliver engineered DNA plasmid or protein to APCs	Potentially toxic / harmful to patients Potential pre-existing immunity Generation of neutralizing antibodies limit the efficacy of repeated administration	[21–31]
Viral vector based	Highly immunogenic Wide range of selection for available vectors Different viral vector possess different immunological properties Can be engineered to include and express costimulatory molecules / cytokines	Potentially toxic / harmful to patients Potential pre-existing immunity Generation of neutralizing antibodies limit the efficacy of repeated administration May elicit immune response mainly targeting viral vector antigens over HPV tumor antigens	[21–22, 32–46]
Peptide based	Stable, safe, easy to produce Can include multiple epitopes Can be modified for better MHC binding	Low immunogenicity Immunogenic epitopes may need to be determined Must match with patient’s MHC class I molecules	[47–50]
Protein based	Stable, safe, easy to produce No MHC Class I restriction	Low immunogenicity Usually better at generating humoral response than cell-mediated response	[47, 49]
DNA based	Stable, safe, easy to produce, store, and transport Capable of repeated administration DNA sequences can be engineered to include targeting and costimulatory genes Multiple delivery methods available Continued expression of antigen from plasmid lead to sustained antigen expression on MHC-peptide complex	Low immunogenicity Potential risk of chromosomal integration Lack intrinsic ability to self amplify and spread to surrounding cells	[51–56]
RNA replicon based	Able to amplify in transfected cells to enhance antigen expression Non-infectious, no risk for chromosomal integration and/or cell cellular transformation Multiple delivery vectors available	Relatively unstable, difficult to store and handle. Stimulate transfected cell to undergo apoptosis; reduced immunogenicity Preparation / production is labor intensive Difficult to prepare in large quantity	[34, 57–63]
DC based	Highly immunogenic Serve as natural adjuvant Multiple methods of antigen loading	Personalized cell processing, labor intensive, costly No standardized quality control and criteria for vaccine preparation	[64–72]
Tumor cell based	Capable of presenting undefined tumor antigen Likely to express relevant tumor antigens	Safety concern for tumor injection in patients Labor intensive preparation Weak antigen presentation Requires autologous tumor cells or availability of tumor cell lines	[8, 73–74]

APCs - antigen presenting cells; MHC - major histocompatibility complex; DC - dendritic cell