Vaccinia-expressed human papillomavirus 16 and 18 e6 and e7 as a therapeutic vaccination for vulval and vaginal intraepithelial neoplasia.
OBJECTIVE
Anogenital intraepithelial neoplasia is a chronic disorder associated with infection by high-risk human papillomavirus (HPV) types. It is frequently multifocal and recurrence after conventional treatment is high. Boosting HPV-specific cell-mediated immune responses may reduce progression to carcinoma and could lead to disease clearance. We have tested the safety, immunogenicity, and efficacy of a recombinant vaccinia candidate vaccine (TA-HPV) in women with anogenital intraepithelial neoplasia.


METHODS
Twelve women, aged 42-54 years with high-grade HPV-positive vulval or vaginal intraepithelial neoplasia of up to 15 years duration, completed a Phase II study of TA-HPV, a live recombinant vaccinia virus, expressing modified versions of the E6 and E7 open reading frames from HPV-16 and HPV-18.


RESULTS
The vaccine was well tolerated. Five of 12 (42%) patients showed at least a 50% reduction in total lesion diameter over 24 weeks with 1 patient showing complete regression of her lesion. Overall, 83% of women showed some improvement with an average decrease in lesion size of 40%. All cases showed an increased IgG titer and T-cell response to the vaccinia virus. An IFN-gamma enzyme-linked immunospot assay using pooled 22-mer peptides spanning HPV-16 E6 and E7 showed an increased specific T-cell response after vaccination in 6 of the 10 cases available for testing. There was no increase in specific cytotoxic response to selected individual HLA class I-restricted HPV-16 E6/7 peptides.


CONCLUSIONS
The results suggest that the vaccine may have an effect on HPV-positive vulval intraepithelial neoplasia/vaginal intraepithelial neoplasia and that additional studies are warranted to develop an effective therapeutic vaccine.
Baldwin
Peter J
PJ
Department of Gynaecological Oncology, Addenbrooke's National Health Service Trust, Cambridge CB2 2QQ, United Kingdom.
van der Burg
Sjoerd H
SH
Boswell
Christopher M
CM
Offringa
Rienk
R
Hickling
Julian K
JK
Dobson
Jennifer
J
Roberts
John St Clair
JS
Latimer
John A
JA
Moseley
Robin P
RP
Coleman
Nicholas
N
Stanley
Margaret A
MA
Sterling
Jane C
JC
D000293:Adolescent; D000328:Adult; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D002278:Carcinoma in Situ / Q000276:immunology / Q000628:therapy* / Q000821:virology; D004268:DNA-Binding Proteins; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology; D027383:Papillomaviridae / Q000235:genetics* / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000276:immunology / Q000628:therapy* / Q000821:virology; D012097:Repressor Proteins; D012449:Safety; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics*; D014625:Vaginal Neoplasms / Q000276:immunology / Q000628:therapy* / Q000821:virology; D014846:Vulvar Neoplasms / Q000276:immunology / Q000628:therapy* / Q000821:virology
D019496:Cancer Vaccines; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; C052633:E7 protein, Human papillomavirus type 18; D015789:HLA-A2 Antigen; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16