Vaccination of healthy volunteers with human papillomavirus type 16 L2E7E6 fusion protein induces serum antibody that neutralizes across papillomavirus species.

2.50
Hdl Handle:
http://hdl.handle.net/10541/72746
Title:
Vaccination of healthy volunteers with human papillomavirus type 16 L2E7E6 fusion protein induces serum antibody that neutralizes across papillomavirus species.
Authors:
Gambhira, Ratish; Gravitt, Patti E; Bossis, Ioannis; Stern, Peter L; Viscidi, Raphael P; Roden, Richard B S
Abstract:
Oncogenic human papillomavirus (HPV) infection is a necessary cause of cervical cancer. Therefore, vaccination to prevent or eliminate HPV infection could reduce the incidence of cervical cancer. A fusion protein comprising HPV16 L2, E6, and E7 is a candidate combination preventive and therapeutic HPV vaccine. The L1- and L2-specific and neutralizing serum antibody titers and peripheral blood mononucleocyte antigen-specific proliferative responses generated by vaccination thrice at monthly intervals with HPV16 L2E7E6 were compared in two studies: a phase I randomized double-blind placebo controlled dose escalation trial in 40 healthy volunteers and a phase II trial of HPV16 L2E7E6 at the maximum dose in 29 women with high-grade anogenital intraepithelial neoplasia (AGIN). Vaccination of healthy volunteers induced L2-specific serum antibodies that were detected 1 month after the final vaccination (P(binomial) < 0.001). There was a significant trend to seroconversion for HPV16 and HPV18 neutralizing antibodies with increasing vaccine dose (P = 0.006 and P = 0.03, respectively). Seroconversion for HPV18 neutralizing antibodies showed a significant positive trend with increasing dose (P = 0.03) and was associated with seroconversion for HPV16 neutralizing antibodies (P(exact) = 0.04). The antigen-specific proliferative response of vaccinated healthy volunteers also showed a significant trend with increasing vaccine dose (P = 0.04). However, AGIN patients responded less effectively to vaccination than healthy patients for induction of HPV16 L2-specific antibody (P < 0.001) and proliferative responses (P < 0.001). Vaccination of healthy volunteers thrice with 533-mug HPV16 L2E7E6 at monthly intervals induced L2-specific serum antibodies that neutralized across papillomavirus species. Responses in AGIN patients were infrequent.
Affiliation:
Department of Pathology, The Johns Hopkins University, Baltimore, Maryland 21231, USA.
Citation:
Vaccination of healthy volunteers with human papillomavirus type 16 L2E7E6 fusion protein induces serum antibody that neutralizes across papillomavirus species. 2006, 66 (23):11120-4 Cancer Res.
Journal:
Cancer Research
Issue Date:
1-Dec-2006
URI:
http://hdl.handle.net/10541/72746
DOI:
10.1158/0008-5472.CAN-06-2560
PubMed ID:
17145854
Type:
Article
Language:
en
ISSN:
0008-5472
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorGambhira, Ratish-
dc.contributor.authorGravitt, Patti E-
dc.contributor.authorBossis, Ioannis-
dc.contributor.authorStern, Peter L-
dc.contributor.authorViscidi, Raphael P-
dc.contributor.authorRoden, Richard B S-
dc.date.accessioned2009-07-07T11:57:37Z-
dc.date.available2009-07-07T11:57:37Z-
dc.date.issued2006-12-01-
dc.identifier.citationVaccination of healthy volunteers with human papillomavirus type 16 L2E7E6 fusion protein induces serum antibody that neutralizes across papillomavirus species. 2006, 66 (23):11120-4 Cancer Res.en
dc.identifier.issn0008-5472-
dc.identifier.pmid17145854-
dc.identifier.doi10.1158/0008-5472.CAN-06-2560-
dc.identifier.urihttp://hdl.handle.net/10541/72746-
dc.description.abstractOncogenic human papillomavirus (HPV) infection is a necessary cause of cervical cancer. Therefore, vaccination to prevent or eliminate HPV infection could reduce the incidence of cervical cancer. A fusion protein comprising HPV16 L2, E6, and E7 is a candidate combination preventive and therapeutic HPV vaccine. The L1- and L2-specific and neutralizing serum antibody titers and peripheral blood mononucleocyte antigen-specific proliferative responses generated by vaccination thrice at monthly intervals with HPV16 L2E7E6 were compared in two studies: a phase I randomized double-blind placebo controlled dose escalation trial in 40 healthy volunteers and a phase II trial of HPV16 L2E7E6 at the maximum dose in 29 women with high-grade anogenital intraepithelial neoplasia (AGIN). Vaccination of healthy volunteers induced L2-specific serum antibodies that were detected 1 month after the final vaccination (P(binomial) < 0.001). There was a significant trend to seroconversion for HPV16 and HPV18 neutralizing antibodies with increasing vaccine dose (P = 0.006 and P = 0.03, respectively). Seroconversion for HPV18 neutralizing antibodies showed a significant positive trend with increasing dose (P = 0.03) and was associated with seroconversion for HPV16 neutralizing antibodies (P(exact) = 0.04). The antigen-specific proliferative response of vaccinated healthy volunteers also showed a significant trend with increasing vaccine dose (P = 0.04). However, AGIN patients responded less effectively to vaccination than healthy patients for induction of HPV16 L2-specific antibody (P < 0.001) and proliferative responses (P < 0.001). Vaccination of healthy volunteers thrice with 533-mug HPV16 L2E7E6 at monthly intervals induced L2-specific serum antibodies that neutralized across papillomavirus species. Responses in AGIN patients were infrequent.en
dc.language.isoenen
dc.subjectAnus Cancer-
dc.subjectFemale Genital Cancer-
dc.subject.meshAdult-
dc.subject.meshAntibodies, Viral-
dc.subject.meshAnus Neoplasms-
dc.subject.meshCapsid Proteins-
dc.subject.meshClinical Trials, Phase I as Topic-
dc.subject.meshClinical Trials, Phase II as Topic-
dc.subject.meshCross Reactions-
dc.subject.meshDouble-Blind Method-
dc.subject.meshEnzyme-Linked Immunosorbent Assay-
dc.subject.meshFemale-
dc.subject.meshGenital Neoplasms, Female-
dc.subject.meshHuman papillomavirus 16-
dc.subject.meshHuman papillomavirus 18-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshNeutralization Tests-
dc.subject.meshOncogene Proteins, Viral-
dc.subject.meshPapillomavirus Infections-
dc.subject.meshPapillomavirus Vaccines-
dc.subject.meshRandomized Controlled Trials as Topic-
dc.subject.meshRecombinant Fusion Proteins-
dc.subject.meshRepressor Proteins-
dc.subject.meshTime Factors-
dc.subject.meshVaccination-
dc.titleVaccination of healthy volunteers with human papillomavirus type 16 L2E7E6 fusion protein induces serum antibody that neutralizes across papillomavirus species.en
dc.typeArticleen
dc.contributor.departmentDepartment of Pathology, The Johns Hopkins University, Baltimore, Maryland 21231, USA.en
dc.identifier.journalCancer Researchen

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