Vaccination of healthy volunteers with human papillomavirus type 16 L2E7E6 fusion protein induces serum antibody that neutralizes across papillomavirus species.
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.
Gambhira
Ratish
R
Department of Pathology, The Johns Hopkins University, Baltimore, Maryland 21231, USA.
Gravitt
Patti E
PE
Bossis
Ioannis
I
Stern
Peter L
PL
Viscidi
Raphael P
RP
Roden
Richard B S
RB
D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D001005:Anus Neoplasms / Q000097:blood / Q000276:immunology / Q000517:prevention & control; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003429:Cross Reactions / Q000276:immunology; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005833:Genital Neoplasms, Female / Q000097:blood / Q000276:immunology / Q000517:prevention & control; D052162:Human papillomavirus 16 / Q000276:immunology; D052161:Human papillomavirus 18 / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000097:blood / Q000276:immunology / Q000517:prevention & control; D053918:Papillomavirus Vaccines / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology*; D013997:Time Factors; D014611:Vaccination / Q000379:methods
D000914:Antibodies, Viral; D036022:Capsid Proteins; C068651:E6 protein, Human papillomavirus type 16; C063316:L2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16