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Effects of varying antigens and adjuvant systems on the immunogenicity and safety of investigational tetravalent human oncogenic papillomavirus vaccines: results from two randomized trials.
- Source :
-
Vaccine [Vaccine] 2014 Jun 17; Vol. 32 (29), pp. 3694-705. Date of Electronic Publication: 2014 Mar 25. - Publication Year :
- 2014
-
Abstract
- Background: A 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.<br />Methods: In 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).<br />Results: One 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.<br />Conclusions: HPV-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.<br /> (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Subjects :
- Adolescent
Adult
Antibodies, Viral blood
Antigens, Viral immunology
B-Lymphocytes immunology
Belgium
Dose-Response Relationship, Immunologic
Double-Blind Method
Drugs, Investigational therapeutic use
Female
Human papillomavirus 16
Human papillomavirus 18
Humans
Immunologic Memory
Papillomavirus Vaccines immunology
United States
Uterine Cervical Neoplasms prevention & control
Uterine Cervical Neoplasms virology
Vaccines, Virus-Like Particle immunology
Vaccines, Virus-Like Particle therapeutic use
Young Adult
Adjuvants, Immunologic administration & dosage
Antibody Formation
Papillomavirus Infections prevention & control
Papillomavirus Vaccines therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2518
- Volume :
- 32
- Issue :
- 29
- Database :
- MEDLINE
- Journal :
- Vaccine
- Publication Type :
- Academic Journal
- Accession number :
- 24674663
- Full Text :
- https://doi.org/10.1016/j.vaccine.2014.03.040