title: Cross-protective vaccine efficacy of the bivalent HPV vaccine against HPV31 is associated with humoral immune responses: results from the Costa Rica Vaccine Trial.
abstract: BACKGROUND
  We investigated the role of antibody responses as potential mechanism for the cross-protective vaccine-efficacies (VE) observed from randomized clinical trials of the HPV16/18 bivalent vaccine. Results HPV31 cases had lower HPV16 antibody levels than controls (OR 4th quartile compared with 1st quartile = 0.63; 95%CI: 0.36-1.08; p-trend = 0.03). HPV31 cases were also less likely to have detectable HPV31 neutralization, and HPV16 avidity than controls. No statistically significant differences by HPV18 antibody or HPV45 neutralization were observed among HPV45 cases and controls. Protection against HPV58 was not associated with any of the markers, confirming the specificity of our findings.
  
  
  METHODS
  Samples are from three-dose HPV vaccine recipients from the Costa Rica HPV16/18 vaccine trial. Women with a new HPV31, HPV45, or HPV58 infections over four years of follow-up were compared with randomly selected control women--with no new infection with HPV31/45/58--with respect to HPV16 and HPV18 antibody, HPV31, HPV45, and HPV58 neutralization, and HPV16 avidity.
  
  
  CONCLUSIONS
  High HPV16 levels and avidity, and the ability to neutralize HPV31 were associated with protection against newly detected HPV31 infections, suggesting that the partial VE demonstrated for HPV31 is likely to be mediated at least in part through antibodies induced by HPV16/18 vaccination.
authors.affiliation: National Cancer Institute; National Institutes of Health; Bethesda, MD USA.
authors.forename: Mahboobeh
authors.initials: M
authors.lastname: Safaeian
authors.forename: Troy J
authors.initials: TJ
authors.lastname: Kemp
authors.forename: David Yuanji
authors.initials: DY
authors.lastname: Pan
authors.forename: Carolina
authors.initials: C
authors.lastname: Porras
authors.forename: Ana Cecilia
authors.initials: AC
authors.lastname: Rodriguez
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.forename: Bernal
authors.initials: B
authors.lastname: Cortes
authors.forename: Hormuzd
authors.initials: H
authors.lastname: Katki
authors.forename: Sholom
authors.initials: S
authors.lastname: Wacholder
authors.forename: John T
authors.initials: JT
authors.lastname: Schiller
authors.forename: Paula
authors.initials: P
authors.lastname: Gonzalez
authors.forename: Kerri
authors.initials: K
authors.lastname: Penrose
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Lowy
authors.forename: Wim
authors.initials: W
authors.lastname: Quint
authors.forename: Leen-Jan
authors.initials: LJ
authors.lastname: van Doorn
authors.forename: Rolando
authors.initials: R
authors.lastname: Herrero
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.forename: Ligia A
authors.initials: LA
authors.lastname: Pinto
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation / Q000276:immunology; D016022:Case-Control Studies; D003364:Costa Rica; D056738:Cross Protection / Q000276:immunology; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology*; D052161:Human papillomavirus 18 / Q000276:immunology*; D058952:Human papillomavirus 31 / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral; D030361:Papillomavirus Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D053918:Papillomavirus Vaccines / Q000276:immunology* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D053918:Papillomavirus Vaccines
keywords: HPV vaccine; cross-protection; humoral; immune response; mechanisms for protection