TY - JOUR
T1 - Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 vaccine and HPV-6/11/16/18 vaccine
T2 - Follow-up from months 12-24 in a phase III randomized study of healthy women aged 18-45 y
AU - Einstein, Mark H.
AU - Baron, Mira
AU - Levin, Myron J.
AU - Chatterjee, Archana
AU - Fox, Bradley
AU - Scholar, Sofia
AU - Rosen, Jeffrey
AU - Chakhtoura, Nahida
AU - Meric, Dorothée
AU - Dessy, Francis J.
AU - Datta, Sanjoy K.
AU - Descamps, Dominique
AU - Dubin, Gary
N1 - Funding Information:
All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf and declare: The submitted work got financial support from GlaxoSmithKline Biologicals.
Funding Information:
A.C., J.R., G.D. received support for travel to meetings for the study. A.C., J.R., M.J.L., N.C. received grants for their institutions. A.C. received financial support for board membership.
Funding Information:
We thank all study participants and their families. This study was sponsored by GlaxoSmithKline Biologicals, Belgium. The team from GlaxoSmithKline Biologicals, US, included Kevin Carrick (Senior Study Manager), J. Ann Jones (Field Monitor), and Joan Adler (Local Medical Monitor). Jesse C. Lepage (Cincinnati Children’s Hospital, Cincinnati, Ohio, United States) provided technical expertise in the preparation of samples for the evaluation of B-cell responses. B-cell assays were performed by the Human Cellular Immunity Team at GlaxoSmithKline Biologicals, Belgium (Olivier Jauniaux, Sarah Charpentier, Valerie Mohy, Dinis Fernandez-Ferreira, Samira Hadiy, Michael P. Mestre, Murielle Carton, Pierre Libert and Luc Franssen). Philippe Moris (GlaxoSmithKline Biologicals, Belgium) led the memory B-cell analysis. Pseudovirion-based neutralization assays and enzyme-linked immunosorbent assays were performed by the Global Vaccine Clinical Laboratories Development Unit (GVCL DU) team at GlaxoSmithKline Biologicals, Belgium (Rudy Crudenaire, Stephanie Abderhamane, Rita Dereymaeker, France Dufranne, Benjamin Mathieu, Marie Gangarossa, Lieve Lauwers, Jeremy Leurquin, Mailys Pringels, Laurence Torset, Jessica Vanderhaegen, Laurence Luyten, Vinciane Lelivre). Sylviane Poncelet (GlaxoSmithKline Biologicals, Belgium) led the enzyme-linked immunosorbent assay analysis of cervicovaginal secretions. Testing of HPV-16 and HPV-18 antibodies in serum was performed by the Global Vaccine Clinical Laboratories Clinical Immunology and Applied Microbiology (GVCL CI&AM) team at GlaxoSmithKline Biologicals, Belgium (Laetitia Gérard, Valérie Smuga, Natacha Casaert, Cathy Hosselet, Aurore Bernis, Gaby Eckstein, Françoise Stevens and Bénédicte Brasseur). Valérie Xhenseval (GlaxoSmithKline Biologicals, Belgium) led the enzyme-linked immunosorbent assay analysis of sera.
PY - 2011/12
Y1 - 2011/12
N2 - In this observer-blind study (NCT00423046), women (N = 1,106), stratified by age (18-26, 27-35, 36-45 y), were randomized (1:1) to receive the HPV-16/18 vaccine (Cervarix® , GlaxoSmithKline Biologicals, Months 0, 1, 6) or the HPV-6/11/16/18 vaccine (Gardasil® Merck and Co., Inc., Months 0, 2, 6). Month 7 results were previously reported; we now report Month 24 results. In the according-to-protocol cohort for immunogenicity (seronegative and DNA-negative at baseline for HPV type analyzed), seropositivity rates of neutralizing antibodies (nAbs) [pseudovirion-based neutralization assay] were, across all age strata, 100% (HPV-16/18 vaccine) and 97.5-100% (HPV-6/11/16/18 vaccine) for HPV-16, and 99.0-100% (HPV-16/18 vaccine) and 72.3-84.4% (HPV-6/11/16/18 vaccine) for HPV-18. Corresponding geometric mean titers (GMTs) were 2.4-5.8-fold higher for HPV-16 and 7.7-9.4-fold higher for HPV-18 with the HPV-16/18 vaccine vs. the HPV-6/11/16/18 vaccine; HPV-16 and HPV-18 GMTs were significantly higher with the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine (p < 0.0001) in the total vaccinated cohort (received ≥1 vaccine dose, irrespective of baseline sero/DNA-status). Similar results were obtained using enzyme-linked immunosorbent assay (ELISA ). Positivity rates and GMTs of antigen-specific IgG antibodies in cervicovaginal secretions (ELISA ) were not significantly different between vaccines. At Month 24, CD4 + T-cell responses for HPV-16 and HPV-18 were higher with the HPV-16/18 vaccine; memory B-cell response was higher for HPV-18 with the HPV-16/18 vaccine and similar between vaccines for HPV-16. Both vaccines were generally well tolerated. Although an immunological correlate of protection has not been defined, differences in the magnitude of immune response between vaccines may represent determinants of duration of protection.
AB - In this observer-blind study (NCT00423046), women (N = 1,106), stratified by age (18-26, 27-35, 36-45 y), were randomized (1:1) to receive the HPV-16/18 vaccine (Cervarix® , GlaxoSmithKline Biologicals, Months 0, 1, 6) or the HPV-6/11/16/18 vaccine (Gardasil® Merck and Co., Inc., Months 0, 2, 6). Month 7 results were previously reported; we now report Month 24 results. In the according-to-protocol cohort for immunogenicity (seronegative and DNA-negative at baseline for HPV type analyzed), seropositivity rates of neutralizing antibodies (nAbs) [pseudovirion-based neutralization assay] were, across all age strata, 100% (HPV-16/18 vaccine) and 97.5-100% (HPV-6/11/16/18 vaccine) for HPV-16, and 99.0-100% (HPV-16/18 vaccine) and 72.3-84.4% (HPV-6/11/16/18 vaccine) for HPV-18. Corresponding geometric mean titers (GMTs) were 2.4-5.8-fold higher for HPV-16 and 7.7-9.4-fold higher for HPV-18 with the HPV-16/18 vaccine vs. the HPV-6/11/16/18 vaccine; HPV-16 and HPV-18 GMTs were significantly higher with the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine (p < 0.0001) in the total vaccinated cohort (received ≥1 vaccine dose, irrespective of baseline sero/DNA-status). Similar results were obtained using enzyme-linked immunosorbent assay (ELISA ). Positivity rates and GMTs of antigen-specific IgG antibodies in cervicovaginal secretions (ELISA ) were not significantly different between vaccines. At Month 24, CD4 + T-cell responses for HPV-16 and HPV-18 were higher with the HPV-16/18 vaccine; memory B-cell response was higher for HPV-18 with the HPV-16/18 vaccine and similar between vaccines for HPV-16. Both vaccines were generally well tolerated. Although an immunological correlate of protection has not been defined, differences in the magnitude of immune response between vaccines may represent determinants of duration of protection.
KW - Cervarix®
KW - Gardasil®
KW - Human papillomavirus
KW - Immunogenicity
KW - Safety
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U2 - 10.4161/hv.7.12.18281
DO - 10.4161/hv.7.12.18281
M3 - Article
C2 - 22048173
AN - SCOPUS:84855181757
VL - 7
SP - 1343
EP - 1358
JO - Human Vaccines
JF - Human Vaccines
SN - 1554-8600
IS - 12
ER -