Effects of varying antigens and adjuvant systems on the immunogenicity and safety of investigational tetravalent human oncogenic papillomavirus vaccines: Results from two randomized trials |
| |
Authors: | Pierre Van Damme Geert Leroux-Roels Philippe Simon Jean-Michel Foidart Gilbert Donders Karel Hoppenbrouwers Myron Levin Fabian Tibaldi Sylviane Poncelet Philippe Moris Francis Dessy Sandra L Giannini Dominique Descamps Gary Dubin |
| |
Institution: | 1. Universiteit Antwerpen, Vaccine & Infectious Disease Institute, Centre for the Evaluation of Vaccination, Building R, 2nd Floor, Universiteitsplein 1, 2610 Antwerpen, Belgium;2. Center for Vaccinology, Ghent University and Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium;3. Service de Gynécologie Obstétrique, Hôpital Erasme, Route de Lennik 808, 1070 Bruxelles, Belgium;4. CHR Citadelle, Service de Gynécologie Obstétrique, Boulevard du 12ieme de Ligne 1, 4000 Liège, Belgium;5. Gynaecologie, Heilig Hartziekenhuis, Kliniekstraat 45, 3300 Tienen, Belgium;6. KULeuven, Jeugdgezondheidszorg, Kapucijnvoer 35/1, 3000 Leuven, Belgium;g University of Colorado School of Medicine, Building 401, 1784 Racine St., Aurora, CO 80045, USA;h GlaxoSmithKline Vaccines, Rue de l’Institut 89, 1330 Rixensart, Belgium;i GlaxoSmithKline Vaccines, Avenue Fleming 20, 1300 Wavre, Belgium;j GlaxoSmithKline SA, 2301 Renaissance Boulevard, RN0220, King of Prussia, PA 19406, USA |
| |
Abstract: | BackgroundA prophylactic human papillomavirus (HPV) vaccine targeting oncogenic HPV types in addition to HPV-16 and -18 may broaden protection against cervical cancer. Two Phase I/II, randomized, controlled studies were conducted to compare the immunogenicity and safety of investigational tetravalent HPV L1 virus-like particle (VLP) vaccines, containing VLPs from two additional oncogenic genotypes, with the licensed HPV-16/18 AS04-adjuvanted vaccine (control) in healthy 18–25 year-old women.MethodsIn one trial (NCT00231413), subjects received control or one of 6 tetravalent HPV-16/18/31/45 AS04 vaccine formulations at months (M) 0,1,6. In a second trial (NCT00478621), subjects received control or one of 5 tetravalent HPV-16/18/33/58 vaccines formulated with different adjuvant systems (AS04, AS01 or AS02), administered on different schedules (M0,1,6 or M0,3 or M0,6).ResultsOne month after the third injection (Month 7), there was a consistent trend for lower anti-HPV-16 and -18 geometric mean antibody titers (GMTs) for tetravalent AS04-adjuvanted vaccines compared with control. GMTs were statistically significantly lower for an HPV-16/18/31/45 AS04 vaccine containing 20/20/10/10 μg VLPs for both anti-HPV-16 and anti-HPV-18 antibodies, and for an HPV-16/18/33/58 AS04 vaccine containing 20/20/20/20 μg VLPs for anti-HPV-16 antibodies. There was also a trend for lower HPV-16 and -18-specific memory B-cell responses for tetravalent AS04 vaccines versus control. No such trends were observed for CD4+ T-cell responses. Immune interference could not always be overcome by increasing the dose of HPV-16/18 L1 VLPs or by using a different adjuvant system. All formulations had acceptable reactogenicity and safety profiles. Reactogenicity in the 7-day post-vaccination period tended to increase with the introduction of additional VLPs, especially for formulations containing AS01.ConclusionsHPV-16 and -18 antibody responses were lower when additional HPV L1 VLPs were added to the HPV-16/18 AS04-adjuvanted vaccine. Immune interference is a complex phenomenon that cannot always be overcome by changing the antigen dose or adjuvant system. |
| |
Keywords: | AE adverse event ANOVA analysis of variance ATP according-to-protocol CD40L CD40 ligand CI confidence interval CIN cervical intraepithelial neoplasia Ctrl control ELISA enzyme-linked immunosorbent assay EU ELISA units GMT geometric mean antibody titer HPV human papillomavirus IFN interferon IL interleukin LU Luminex units M months MLIA multiplex Luminex immunoassay MPL 3-O-desacyl-4&prime -monophosphoryl lipid A No number PBNA pseudovirion-based neutralization assay PCR polymerase chain reaction QS21 Quillaja saponaria Molina fraction 21 SAE serious adverse event TNF tumor necrosis factor VLP virus-like particle |
本文献已被 ScienceDirect 等数据库收录! |
|