Serological response to an HPV16 E7 based therapeutic vaccine in women with high-grade cervical dysplasia.
OBJECTIVE
Infection with oncogenic human papillomaviruses has been linked to the development of cervical neoplasia and cancer. The exclusive expression of E7, a viral oncogene, in infected cells makes this protein an ideal target for immunotherapy. We recently reported on the results of a trial in women with cervical carcinoma-in-situ using HspE7, a protein vaccine consisting of full length HPV16 E7 linked to a heat shock protein from M. bovis. The stimulating effects of HspE7 on specific cytotoxic T lymphocytes have been demonstrated in vitro and in (pre-)clinical trials. The induction of a B-cell response by HspE7 and its association with clinical outcome is unknown, and is the purpose of this study.


METHODS
We measured the serum IgG levels against HPV16 E7 and HPV16 and -18 VLPs using a multiplexed Luminex based assay in 57 women with CIS who received the HspE7 vaccine.


RESULTS
Vaccination with HspE7 results in a modest, yet maintained increase in HPV16 E7 specific IgG levels. While not significant, increased HPV16 E7 IgG levels appear to be correlated with a positive therapeutic effect. Women who were previously treated for recurrent disease (by LEEP) had significantly higher HPV16 E7 IgG levels compared with subjects without recurrent disease (p=0.01). In women with recurrent disease, higher IgG levels correlated with complete pathological response.


CONCLUSIONS
This study suggests that IgG levels could potentially be used as a marker for response to a therapeutic vaccine. Further translational investigations of the 'priming' of local immune responses using extirpative procedures should be explored.
Van Doorslaer
Koenraad
K
Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. kdoorsla@aecom.yu.edu
Reimers
Laura L
LL
Studentsov
Yevgeniy Y
YY
Einstein
Mark H
MH
Burk
Robert D
RD
D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D018834:Chaperonin 60 / Q000276:immunology; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D009163:Mycobacterium bovis / Q000276:immunology; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000276:immunology / Q000473:pathology; D053918:Papillomavirus Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D002578:Uterine Cervical Dysplasia / Q000276:immunology / Q000628:therapy* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000628:therapy* / Q000821:virology
D000914:Antibodies, Viral; D001426:Bacterial Proteins; D019496:Cancer Vaccines; D018834:Chaperonin 60; D007074:Immunoglobulin G; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; C074119:heat-shock protein 65, Mycobacterium; C059731:oncogene protein E7, Human papillomavirus type 16