title: Sustained Antibody Responses 6 Years Following 1, 2, or 3 Doses of Quadrivalent Human Papillomavirus (HPV) Vaccine in Adolescent Fijian Girls, and Subsequent Responses to a Single Dose of Bivalent HPV Vaccine: A Prospective Cohort Study.
abstract: BACKGROUND
  The duration of antibody response following reduced human papillomavirus (HPV) vaccine doses has not been determined. We compared the antibody responses in girls previously vaccinated with zero, 1, 2, or 3 doses of quadrivalent HPV vaccine (4vHPV; Gardasil, Merck) 6 years previously.
  
  
  METHODS
  A prospective cohort study was undertaken in 200 Fijian girls 15-19 years of age. Approximately equal numbers of girls from 2 main ethnic groups (Fijians of Indian descent [FID] and Indigenous Fijians [iTaukei]) in Fiji were recruited for each dosage groups. Blood was drawn before and 28 days following a single dose of bivalent HPV vaccine (2vHPV; Cervarix, GlaxoSmithKline). We measured neutralizing antibodies (NAb) against HPV-6, -11, -16, and -18 using the pseudovirion-based neutralization assay.
  
  
  RESULTS
  After 6 years (before a dose of 2vHPV was given), the geometric mean NAb titers for all 4 HPV types were not statistically different between 2-dose (2D) and 3-dose (3D) recipients: HPV-6 (3D: 2216 [95% confidence interval {CI},1695-2896]; 2D: 1476 [95% CI, 1019-2137]; P = .07), HPV-11 (3D: 4431 [95% CI, 3396-5783]; 2D: 2951 [95% CI, 1984-4390]; P = .09), HPV-16 (3D: 3373 [95% CI, 2511-4530]; 2D: 3275 [95% CI, 2452-4373]; P = .89); HPV-18 (3D: 628 [95% CI: 445-888]; 2D: 606 [95% CI, 462-862]; P = .89), and were higher in FID than iTaukei girls. Although 1-dose recipients had significantly lower NAb titers than 2-/3-dose recipients, their NAb titers were 5- to 30-fold higher than unvaccinated girls. Post-2vHPV NAb titers against HPV-16 and -18 were not statistically different between girls who received 1, 2, or 3 doses of 4vHPV previously.
  
  
  CONCLUSIONS
  Two doses of 4vHPV provide similar NAb titers as 3 doses for 6 years, although the clinical significance is unknown. A single dose of 4vHPV elicits antibodies that persisted for at least 6 years, and induced immune memory, suggesting possible protection against HPV vaccine types after a single dose of 4vHPV.
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, and.
authors.forename: Zheng Quan
authors.initials: ZQ
authors.lastname: Toh
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, and.|Centre for International Child Health, Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Russell
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, and.
authors.forename: Rita
authors.initials: R
authors.lastname: Reyburn
authors.affiliation: Ministry of Health and Medical Services, Suva, Fiji.
authors.forename: James
authors.initials: J
authors.lastname: Fong
authors.affiliation: Ministry of Health and Medical Services, Suva, Fiji.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Tuivaga
authors.affiliation: Ministry of Health and Medical Services, Suva, Fiji.
authors.forename: Tupou
authors.initials: T
authors.lastname: Ratu
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, and.
authors.forename: Cattram D
authors.initials: CD
authors.lastname: Nguyen
authors.affiliation: Ministry of Health and Medical Services, Suva, Fiji.
authors.forename: Rachel
authors.initials: R
authors.lastname: Devi
authors.affiliation: Ministry of Health and Medical Services, Suva, Fiji.
authors.forename: Mike
authors.initials: M
authors.lastname: Kama
authors.affiliation: Ministry of Health and Medical Services, Suva, Fiji.
authors.forename: Silivia
authors.initials: S
authors.lastname: Matanitobua
authors.affiliation: Department of Obstetrics and Gynecology, University of Melbourne, Royal Women's Hospital and Murdoch Childrens Research Institute, and.|Department of Microbiology and Infectious Disease, Royal Women's Hospital Regional World Health Organization HPV Reference Laboratory, Parkville, Victoria, and.
authors.forename: Sepehr N
authors.initials: SN
authors.lastname: Tabrizi
authors.affiliation: Department of Obstetrics and Gynecology, University of Melbourne, Royal Women's Hospital and Murdoch Childrens Research Institute, and.|Department of Microbiology and Infectious Disease, Royal Women's Hospital Regional World Health Organization HPV Reference Laboratory, Parkville, Victoria, and.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Garland
authors.affiliation: University of Queensland Diamantina Institute, Brisbane,Australia.
authors.forename: Rohit
authors.initials: R
authors.lastname: Sinha
authors.affiliation: University of Queensland Diamantina Institute, Brisbane,Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: Frazer
authors.affiliation: Ministry of Health and Medical Services, Suva, Fiji.
authors.forename: Lisi
authors.initials: L
authors.lastname: Tikoduadua
authors.affiliation: Ministry of Health and Medical Services, Suva, Fiji.
authors.forename: Joseph
authors.initials: J
authors.lastname: Kado
authors.affiliation: Ministry of Health and Medical Services, Suva, Fiji.
authors.forename: Eric
authors.initials: E
authors.lastname: Rafai
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, and.|London School of Hygiene and Tropical Medicine, United Kingdom; and.|Department of Child Health, Menzies School of Health Research, Darwin, Northern Territory, Australia.
authors.forename: Edward K
authors.initials: EK
authors.lastname: Mulholland
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, and.|Centre for International Child Health, Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Paul V
authors.initials: PV
authors.lastname: Licciardi
mesh_terms: D000293:Adolescent; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D002648:Child; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005367:Fiji / Q000453:epidemiology; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18 / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D027383:Papillomaviridae / Q000276:immunology*; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D011446:Prospective Studies; D012959:Socioeconomic Factors
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D053918:Papillomavirus Vaccines; C510352:human papillomavirus vaccine, L1 type 16, 18
keywords: adolescents; human papillomavirus vaccine; immune memory; neutralizing antibodies; reduced doses