Table 1.

Summary of the advantages and disadvantages of therapeutic vaccines

Therapeutic vaccine	Description	Advantages	Disadvantages	References
Live vector–based	Highly immunogenic attenuated bacterial or viral vectors that carry recombinant DNA encoding the antigen of interest into the host to elicit an immune response. Bacterial vectors such as Listeria monocytogenes and viral vectors such as the vaccinia virus have been shown to generate potent humoral and cellular immune responses in pre-clinical models	• Highly immunogenic • Mimics natural course of infection	• Preexisting immunity against vector • No repeated administration • Safety risks for immunocompromized individuals	15, 33–42
Peptide-/protein-based	Peptide-based vaccines are peptide segments containing epitopes of tumor-associated antigens or other antigenic proteins of interest while protein-based vaccines are the antigenic proteins themselves.	Peptide-based: • Safe • Stable • Easy to produce Protein-based: • Safe • Stable • Easy to produce • No HLA restriction	Peptide-based: • HLA restriction • Low immunogenicity • Requires co-administration of adjuvants Protein-based: • Low immunogenicity • Requires co-administration of adjuvants • Generates antibodies instead of cytotoxic T lymphocytes	15, 43–46
Whole cell–based	Whole cell vaccines involve the adoptive transfer of autologous dendritic or tumor cells that have been prepared to express the target antigens and other costimulatory molecules. In dendritic cell (DC)-based vaccines, DCs are loaded with HPV antigens ex vivo and delivered into the patient. Tumor cell-based vaccines aim to improve the immunogenicity of tumor cells by increasing the expression of immune modulatory proteins, such as IL-2, IL-12, and GM-CSF.	DC-based: • Highly immunogenic Tumor cell-based: • Likely to express tumor antigens	• Expensive • Labor intensive • Safety concerns	47–50
Nucleic acid–based (RNA-based only)	RNA replicon vaccines involve the insertion of an RNA sequence encoding the target antigens into disabled viral vectors derived from RNA viruses such as the Sindbis virus, Venezuelan Equine Encephalitis virus, and Simian Foamy virus.	• Transient infections • Multiple administrations • Sustained antigen expression • No risk of chromosomal integration and cellular transformation	• Difficult to produce and store • Unstable • Labor intensive • No intercellular spreading • Dose-limiting toxicities • Multiple mRNAs cannot be combined in the same formulation • Human safety data for RNA has not been well developed	51–54

GM-CSF, granulocyte-macrophage colony-stimulating factor; HLA, human leukocyte antigen; HPV, human papilloma virus; IL, interleukin.