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

Clin Infect Dis. 2017 Apr 1;64(7):852-859. doi: 10.1093/cid/ciw865.

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.

Keywords: adolescents; human papillomavirus vaccine; immune memory; neutralizing antibodies; reduced doses.

MeSH terms

  • Adolescent
  • Antibodies, Neutralizing
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology*
  • Child
  • Dose-Response Relationship, Immunologic
  • Female
  • Fiji / epidemiology
  • Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18 / administration & dosage
  • Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18 / immunology*
  • Humans
  • Immunization, Secondary
  • Papillomaviridae / immunology*
  • Papillomavirus Infections / epidemiology
  • Papillomavirus Infections / prevention & control*
  • Papillomavirus Vaccines / administration & dosage
  • Papillomavirus Vaccines / immunology*
  • Prospective Studies
  • Socioeconomic Factors

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18
  • Papillomavirus Vaccines
  • human papillomavirus vaccine, L1 type 16, 18