Table 2.: Clinical Studies with Therapeutic HPV Vaccines

Type of Vaccine Composition / Adjuvant Via Phase of Study Patients Immune Response Clinical Response Refs.
Peptide vaccines HPV-16 E786-93 peptide conjugated with lipid (palmitic acid) linked to the non-specific PADRE helper peptide ADDIN EN.CITE ADDIN EN.CITE.DATA [65, 66] SC I 12 patients (HLA-A*0201) with refractory cervical or vaginal cancer E7-specific CTL response in 7 patients No clinical response a
Two HPV-16 E7 peptides (E712-20 and E786-93) linked to the non-specific PADRE helper peptide Adjuvant: IFA SC I-II 19 cervical cancer patients (HLA-A*0201) No E7-specific CTL response 2 partial remissions b
E712-20 and E786-93 Peptides linked to the PADRE helper peptide bound to a lipid radicalAdjuvant : IFA SC I 18 patients (HLA-A*0201) with high-grade cervical or vulvar intraepithelial neoplasia E7-specific CTL response in 10 patients 3 complete remissions9 partial remissions c
Protein vaccines Fusion protein containing HPV-16 E7 and HSP-65 ofMycobacterium Bovis BCG SC II 22 anal HSIL patients, of which 14 presented anogenital condiloma Non-determined 3 complete remissions10 partial remissions d
Fusion protein containing HPV-16 L2, E6 and E7(TA-CIN) IM I 40 healthy volunteers E6 and E7-specific CTL responses in 8 patients Not determined e
Three doses ofTA-CIN, followed by one dose of TA-HPV (see below Viral Vector Vaccines)(Prime-boost trial) IM II 29
Fusion protein containing HPV-16 E6 and E7 Adjuvant: ISCOMATRIX® ADDIN EN.CITE ADDIN EN.CITE.DATA IM I 8 CIN I patients10 CIN II patients NIC II13 CIN III patients Specific CTL responses in 5 patientsDelayed type hypersensitivity (DTH)To E6 and E7 in 18 patients 4 complete remissions f
Fusion protein containing an HPV-16 E7 mutant conjugated to the Haemophilus influenzae protein D (PD-E7)Adjuvant : AS02B IM I/II 5 CIN III patients2 CIN I patients Increase of preexisting cellular response to PD-E7 in 5 patients 2 remissions(CIN I patients) g
Dendritic cell vaccines Autologous DCs loaded with recombinant HPV-16 or HPV-18 E7 protein SC I 15 grade IV cervical cancer patients CTL responses in 4 patientsAntibody responses in 3 patients No h
DCs loaded with HPV-16 E7 or HPV-18and human recombinant IL-2 SC I 4 cervical cancer patients (HPV-16+ or HPV-18+) refractory to standard treatment Specific antibody and CD4+ T lymphocytes in 2 patientsIncrease in E7-specific CD8+ T cellsin 4 patients No i
DNA vaccines ZYC101: Zycos 101 plasmid DNA encoding several HLA-A2 epítopes from HPV-16 E7 Encapsulated in microparticles of biodegradable polymer IM I 12 anal dysplasia patients Increasedresponses to E7 epitopes in10 cases 3 partial remissions j
ZYC101 SC / IM I 15 CIN II/III patients 11 HPV-specific CTL responses 5 complete remissions k
Amolimogene/ZYC101a: plasmid DNA encoding fragments from HPV-16 and 18 E6 and E7Encapsulated in microparticles of biopolymer IM II 127 CIN II/III patients(86 under treatment) 80 Increased preexisting specific T cell responses 37 complete remissions l
Viral vector vaccines TA-HPV vaccine: vaccinia virus strain Wyeth encoding a HPV 16 and 18 E6/ E7 fusion protein Dermal scarification I 8 advanced cervical cancer patients (grades Ib-IIIb or recurrent) 3 humoral responses against E6/E7, and 8 anti-vaccinia1 HPV-specific CTL response No m
TA-HPV Dermal scarification I 29 cervical cancer patients (grade Ib o IIa) 8 HPV-specific antibody responses4 HPV-specific CTL responses No n
TA-HPV Dermal scarification II 12 VIN patients 6 CD4+ T lymphocyte responses10 HPV-specific antibody responses 5 partial remissions1 complete remission o
TA-HPV Dermal scarification II 18 high grade VIN patients 8 T cell proliferation responses5 INF-g response1 humoral response 8 partial remissions p
MVA-E2 Intra- uterus I-II 36 CIN I, II or III patients Humoral and cellular responses in all cases 34 complete remissions q
MVA-E2 Intra-uterus II 34 CIN II or III patients Humoral and cellular responses in all cases 20 complete remissions11 partial remissions r
MVA-HPV-IL2: recombinant Modified Vaccinia Virus Ankara (MVA), attenuated vaccinia strain, encoding modified E6 y E7 proteins and IL-2 IM II 31 CIN II/III patients Not reported 5 partial remissions s
MVA-HPV-IL2 SC II 21 CIN II/III patients Not reported 10 partial remissions t

Abbreviations: aa: amino acid; IFA: Incomplete Freund’s Adjuvant; HPV: Human papillomavirus; IL-2: interleukine-2; IM: Intramuscular; HSIL: high grade squamous intraepitelial lesion; CIN: cervical intraepithelial neoplasia; VIN: Vulvar/vaginal intraepitelial neoplasia; SC: subcutaneous.(a) [64].(b) [67,126](c) [68].(d) [69].(e) [75].(f) [80].(g) [82].(h) [87].(i) [88].(j) [91].(k) [92].(l) [93].(m) [98].(n) [99].(o) [100].(p) [101].(q) [102].(r) [103].(s) [108].(t) [115].