Dna

Highly immunogenic Can take advantage of the different immunological properties of viruses Wide variety of vectors available (i.e., vaccinia, adv, AAV, alphavirus) Can be engineered to express cytokines of other stimulatory molecules

Highly immunogenic Can deliver either engineered plasmids of HPV tumor proteins to APCs Wide variety of vectors are available (i.e., Listeria, Salmonella, BCG, Lactococcus) Easy to produce, store, and transport Versatility in ability to add targeting and/or costimulatory genes Multiple immunizations possible

Risk of toxicity when using live viruses Potential pre-existing immunity Inhibited repeat immunization Immunodominance of viral vector antigens on HPV tumor antigens

Risk of toxicity when using live bacteria Potential pre-existing immunity Inhibited repeat immunization

Study in patients with early-stage cervical cancer (93), late stage cervical cancer (92) and HPV-positive vaginal or vulvar intraepithelial neoplasia (94,95) to assess the safety and immunological effects of vaccination with TA-HPV, a live recombinant vaccinia virus expressing modified forms of the HPV-16 and -18 E6 and E7 proteins Study in patients with CIN (Grades I—III) to assess the safety and immunogenicity of intrauterine immunization with MVA E2 recombinant vaccinia virus vaccine (96)

Intrinsically weak immunogen Concern of integration or cellular tranformation

Study in subjects with anal HPV-16 infection (97) and high-grade CIN (98) evaluating the safety and immunogencity of ZYC101, an encapsulated plasmid DNA vaccine encoding multiple HLA-A2-restricted epitopes derived from the HPV-16 E7 protein

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Approach

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