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 |