title: Durable antibody responses following one dose of the bivalent human papillomavirus L1 virus-like particle vaccine in the Costa Rica Vaccine Trial.
abstract: The Costa Rica HPV16/18 Vaccine Trial (CVT) showed that four-year vaccine efficacy against 12-month HPV16/18 persistent infection was similarly high among women who received one, two, or the recommended three doses of the bivalent HPV16/18 L1 virus-like particle (VLP) vaccine. Live-attenuated viral vaccines, but not simple-subunit vaccines, usually induce durable lifelong antibody responses after a single dose. It is unclear whether noninfectious VLP vaccines behave more like live-virus or simple-subunit vaccines in this regard. To explore the likelihood that efficacy will persist longer term, we investigated the magnitude and durability of antibodies to this vaccine by measuring HPV16- and HPV18-specific antibodies by VLP-ELISA using serum from enrollment, vaccination, and annual visits through four years in four vaccinated groups; one-dose (n = 78), two-doses separated by one month (n = 140), two doses separated by six months (n = 52), and three scheduled doses (n = 120, randomly selected). We also tested enrollment sera from n = 113 HPV16- or HPV18 L1-seropositive women prevaccination, presumably from natural infection. At four years, 100% of women in all groups remained HPV16/18 seropositive; both HPV16/18 geometric mean titers (GMT) among the extended two-dose group were non-inferior to the three-dose group, and ELISA titers were highly correlated with neutralization titers in all groups. Compared with the natural infection group, HPV16/18 GMTs were, respectively, at least 24 and 14 times higher among the two-dose and 9 and 5 times higher among one-dose vaccinees. Antibody levels following one-dose remained stable from month 6 through month 48. Results raise the possibility that even a single dose of HPV VLPs will induce long-term protection.
authors.affiliation: Division of Cancer Epidemiology and Genetics, Infections and Immunoepidemiology Branch, National Cancer Institute, 9609 Medical Center Drive, Rm 6-E224, MSC 9767, Bethesda, MD 20892. safaeianm@mail.nih.gov.
authors.forename: Mahboobeh
authors.initials: M
authors.lastname: Safaeian
authors.forename: Carolina
authors.initials: C
authors.lastname: Porras
authors.forename: Yuanji
authors.initials: Y
authors.lastname: Pan
authors.forename: Aimee
authors.initials: A
authors.lastname: Kreimer
authors.forename: John T
authors.initials: JT
authors.lastname: Schiller
authors.forename: Paula
authors.initials: P
authors.lastname: Gonzalez
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Lowy
authors.forename: Sholom
authors.initials: S
authors.lastname: Wacholder
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.forename: Ana C
authors.initials: AC
authors.lastname: Rodriguez
authors.forename: Rolando
authors.initials: R
authors.lastname: Herrero
authors.forename: Troy
authors.initials: T
authors.lastname: Kemp
authors.forename: Gloriana
authors.initials: G
authors.lastname: Shelton
authors.forename: Wim
authors.initials: W
authors.lastname: Quint
authors.forename: Leen-Jan
authors.initials: LJ
authors.lastname: van Doorn
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.forename: Ligia A
authors.initials: LA
authors.lastname: Pinto
mesh_terms: D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D000917:Antibody Formation; D003364:Costa Rica; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D027383:Papillomaviridae / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D053918:Papillomavirus Vaccines / Q000627:therapeutic use*; D058425:Vaccines, Virus-Like Particle / Q000627:therapeutic use*
chemical_list: D000914:Antibodies, Viral; D053918:Papillomavirus Vaccines; D058425:Vaccines, Virus-Like Particle