Table 1.

Advantages and disadvantages of HPV therapeutic vaccines

Vaccine approach	Advantages	Disadvantages
Viral vector-based	High immunogenicity Wide variety of vectors available Can facilitate intracellular antigen spreading Different immunological properties of viruses	Risk of toxicity in using live viruses Potential pre-existing immunity may inhibit repeated administration Possible dominance of immune response to viral vector rather than HPV antigen
Bacterial vector-based	High immunogenicity Can deliver either engineered plasmids or HPV tumor proteins to APCs Wide variety of vectors available	Risk of toxicity in using live bacteria Potential pre-existing immunity Inhibited repeat immunization
Peptide-based	Easy to produce, stable, safe Can combine multiple epitopes Can engineer peptides for enhanced MHC binding	Low immunogenicity Epitopes must be determined HLA-restriction Difficult to have one-fits-all peptide
Protein-based	Stable, safe, easy to produce No HLA restriction Multiple known adjuvants	Low immunogenicity; requires adjuvant Usually better induction of antibody response than CTL response
DNA-based	Safe, easy to produce, stable for storage and transportation Capacity for repeated administration Easy to prepare at high purity Several delivery methods possible Sustained expression of antigen on MHC-peptide complex Can be engineered to add targeting and/or co-stimulatory genes	No intercellular spreading immunogenicity Risk of integration into genome or cellular transformation
RNA-based	Non-infectious, no risk of genomic integration or cellular transformation Transient Can administer multiple times Enhanced antigen expression Multiple vectors are available	Unstable, difficulty in long-term storage Labor intensive preparation Difficult to prepare large amounts No intercellular spreading
Dendritic cell-based	High immunogenicity; uses the most potent APCs Multiple methods available to load antigen Efficient antigen presentation Potency can be enhanced by gene transduction or cytokine treatment	Labor intensive, expensive, ex vivo, individualized cell processing Variable quality control and a lack of agreed standards for quality of vaccines Difficult to produce on a large scale DCs do not necessarily home to lymph nodes
Tumor cell-based	Useful if tumor antigen unknown Likely to express tumor antigens Potency can be enhanced by cytokine treatment	Safety concerns about injecting tumor cells into patients Labor intensive as it is individualized Costly, difficult to produce on a large scale Requires availability of tumor cell lines or autologous tumor cells