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

Ratish Gambhira, Patti E. Gravitt, Ioannis Bossis, Peter L. Stern, Raphael P. Viscidi, Richard B S Roden

    Research output: Contribution to journalArticlepeer-review

    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 (Pbinomial <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 (Pexact = 0.04). The antigen-specific proliferative response of vaccinated healthy volunteers also showed a significant trend with increasing vaccine dose (P = 0.04). However, AGTN 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-μg HPV16 L2E7E6 at monthly intervals induced L2-specific serum antibodies that neutralized across papillomavirus species. Responses in AGIN patients were infrequent. ©2006 American Association for Cancer Research.
    Original languageEnglish
    Pages (from-to)11120-11124
    Number of pages4
    JournalCancer Research
    Volume66
    Issue number23
    DOIs
    Publication statusPublished - 1 Dec 2006

    Keywords

    • Adult
    • blood: Antibodies, Viral
    • blood: Anus Neoplasms
    • genetics: Capsid Proteins
    • Clinical Trials, Phase I
    • Clinical Trials, Phase II
    • immunology: Cross Reactions
    • Double-Blind Method
    • Enzyme-Linked Immunosorbent Assay
    • Female
    • blood: Genital Neoplasms, Female
    • immunology: Human papillomavirus 16
    • immunology: Human papillomavirus 18
    • Humans
    • Male
    • Middle Aged
    • Neutralization Tests
    • genetics: Oncogene Proteins, Viral
    • blood: Papillomavirus Infections
    • administration & dosage: Papillomavirus Vaccines
    • Randomized Controlled Trials
    • immunology: Recombinant Fusion Proteins
    • genetics: Repressor Proteins
    • Time Factors
    • methods: Vaccination

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