title: Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle (VLP) vaccine.
abstract: BACKGROUND
  The duration of protection afforded by vaccines represents a critical test of their utility as public health interventions. Some vaccines induce long-term immunity, while others require booster doses. Vaccines that induce long-term protection are usually characterized by the generation of immune memory. Recent trials of a quadrivalent (types 6, 11, 16, 18) human papillomavirus (HPV) vaccine have demonstrated high efficacy through 5 years of follow-up. We evaluated the extent to which the vaccine is able to generate HPV type-specific immune memory.
  
  
  METHODS
  A total of 552, 16-23-year-old women were enrolled in a double-blind, placebo-controlled study. At enrollment, subjects were randomized in a 1:1 ratio to receive three-dose regimens of quadrivalent HPV vaccine or placebo with 3 years' follow-up. A subset of 241 subjects (n=114 in the quadrivalent HPV vaccine group and n=127 in the placebo group) underwent 2 further years of follow-up. All extension subjects received quadrivalent HPV vaccine at month 60 to examine the extent of immune memory in response to the primary vaccination series.
  
  
  RESULTS
  Serum anti-HPV levels declined post-vaccination, but reached a plateau at month 24 that remained stable through month 60. Administration of a challenge dose of vaccine induced a classic anamnestic response, with anti-HPV levels 1 week post-challenge reaching levels observed 1 month following the completion of the three-dose primary series. At 1 month post-challenge, anti-HPV responses were higher than those observed 1-month post-dose 3.
  
  
  CONCLUSIONS
  A three-dose regimen of quadrivalent HPV vaccine induces high efficacy and stable anti-HPV levels for at least 5 years. Vaccination also induces robust immune memory. These findings suggest that the efficacy of this vaccine will be long lasting.
authors.affiliation: Karolinska Institute at Danderyds Hospital, SE-182 88 Danderyd, Sweden. sven-eric.olsson@ds.se
authors.forename: Sven-Eric
authors.initials: SE
authors.lastname: Olsson
authors.forename: Luisa L
authors.initials: LL
authors.lastname: Villa
authors.forename: Ronaldo L R
authors.initials: RL
authors.lastname: Costa
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Petta
authors.forename: Rosires P
authors.initials: RP
authors.lastname: Andrade
authors.forename: Christian
authors.initials: C
authors.lastname: Malm
authors.forename: Ole-Erik
authors.initials: OE
authors.lastname: Iversen
authors.forename: John
authors.initials: J
authors.lastname: Høye
authors.forename: Margareta
authors.initials: M
authors.lastname: Steinwall
authors.forename: Grete
authors.initials: G
authors.lastname: Riis-Johannessen
authors.forename: Agneta
authors.initials: A
authors.lastname: Andersson-Ellstrom
authors.forename: Kristina
authors.initials: K
authors.lastname: Elfgren
authors.forename: Geo
authors.initials: G
authors.lastname: von Krogh
authors.forename: Matti
authors.initials: M
authors.lastname: Lehtinen
authors.forename: Jorma
authors.initials: J
authors.lastname: Paavonen
authors.forename: Gretchen M
authors.initials: GM
authors.lastname: Tamms
authors.forename: Katherine
authors.initials: K
authors.lastname: Giacoletti
authors.forename: Lisa
authors.initials: L
authors.lastname: Lupinacci
authors.forename: Mark T
authors.initials: MT
authors.lastname: Esser
authors.forename: Scott C
authors.initials: SC
authors.lastname: Vuocolo
authors.forename: Alfred J
authors.initials: AJ
authors.lastname: Saah
authors.forename: Eliav
authors.initials: E
authors.lastname: Barr
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005500:Follow-Up Studies; D052140:Human papillomavirus 11 / Q000276:immunology; D052162:Human papillomavirus 16 / Q000276:immunology; D052161:Human papillomavirus 18 / Q000276:immunology; D006801:Humans; D007115:Immunization Schedule; D007156:Immunologic Memory / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology* / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D053918:Papillomavirus Vaccines