Comparison of long-term immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine in healthy women aged 18-45 years: End-of-study analysis of a Phase III randomized trial

Mark H. Einstein, Peter Takacs, Archana Chatterjee, Rhoda S. Sperling, Nahida Chakhtoura, Mark M. Blatter, Jacob Lalezari, Marie Pierre David, Lan Lin, Frank Struyf, Gary Dubin

Research output: Contribution to journalArticle

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Abstract

The observer-blind, randomized, age-stratified, head-to-head study (NCT00423046) comparing immunogenicity and safety of HPV-16/18 and HPV-6/11/16/18 vaccines in healthy women aged 18-45 y was completed. Five y after vaccination, in subjects from the Month 60 according-to-protocol cohort (seronegative and DNA negative for HPV type analyzed at baseline), serum neutralizing antibody (nAb) responses induced by HPV-16/18 vaccine remained 7.8-fold (18-26-y stratum), 5.6-fold (27-35-y stratum) and 2.3-fold (36-45-y stratum) higher than those induced by HPV-6/11/16/18 vaccine for HPV-16. For HPV-18, the fold differences were 12.1, 13.0 and 7.8, respectively. At Month 60, all (100%) subjects in HPV-16/18 vaccine group and the majority (95.7%-97.5%) in HPV-6/11/16/18 vaccine group were seropositive for HPV-16. For HPV-18, the majority (98.1%-100%) of subjects in HPV-16/18 vaccine group were seropositive; however, seropositivity rates in HPV-6/11/16/18 vaccine group decreased considerably (61.1%-76.9%) across the 3 age strata. In the total vaccinated cohort (received ≥ 1 dose regardless of baseline HPV serostatus and DNA status), geometric mean titers for anti-HPV-16 and anti-HPV-18 nAb were higher in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. Based on the 5-y data, piece-wise and modified power-law models predicted a longer durability of nAb response for HPV-16/18 vaccine compared to HPV-6/11/16/18 vaccine. Beyond the differences apparent between the vaccines in terms of immunogenicity and modeled persistence of antibody responses, comparative studies including clinical endpoints would be needed to determine whether differences exist in duration of vaccine-induced protection.

Original languageEnglish (US)
Pages (from-to)3435-3445
Number of pages11
JournalHuman Vaccines and Immunotherapeutics
Volume10
Issue number12
DOIs
StatePublished - Dec 1 2014

Fingerprint

Human papillomavirus 11
Human papillomavirus 6
Human papillomavirus 18
Human papillomavirus 16
Vaccines
Safety
Neutralizing Antibodies
Antibody Formation
DNA

Keywords

  • Antibodies
  • Cervarix®
  • Gardasil®
  • Human papillomavirus
  • Immunogenicity
  • Models
  • Neutralizing
  • Safety
  • Statistical

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

Comparison of long-term immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine in healthy women aged 18-45 years : End-of-study analysis of a Phase III randomized trial. / Einstein, Mark H.; Takacs, Peter; Chatterjee, Archana; Sperling, Rhoda S.; Chakhtoura, Nahida; Blatter, Mark M.; Lalezari, Jacob; David, Marie Pierre; Lin, Lan; Struyf, Frank; Dubin, Gary.

In: Human Vaccines and Immunotherapeutics, Vol. 10, No. 12, 01.12.2014, p. 3435-3445.

Research output: Contribution to journalArticle

Einstein, Mark H. ; Takacs, Peter ; Chatterjee, Archana ; Sperling, Rhoda S. ; Chakhtoura, Nahida ; Blatter, Mark M. ; Lalezari, Jacob ; David, Marie Pierre ; Lin, Lan ; Struyf, Frank ; Dubin, Gary. / Comparison of long-term immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine in healthy women aged 18-45 years : End-of-study analysis of a Phase III randomized trial. In: Human Vaccines and Immunotherapeutics. 2014 ; Vol. 10, No. 12. pp. 3435-3445.
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abstract = "The observer-blind, randomized, age-stratified, head-to-head study (NCT00423046) comparing immunogenicity and safety of HPV-16/18 and HPV-6/11/16/18 vaccines in healthy women aged 18-45 y was completed. Five y after vaccination, in subjects from the Month 60 according-to-protocol cohort (seronegative and DNA negative for HPV type analyzed at baseline), serum neutralizing antibody (nAb) responses induced by HPV-16/18 vaccine remained 7.8-fold (18-26-y stratum), 5.6-fold (27-35-y stratum) and 2.3-fold (36-45-y stratum) higher than those induced by HPV-6/11/16/18 vaccine for HPV-16. For HPV-18, the fold differences were 12.1, 13.0 and 7.8, respectively. At Month 60, all (100{\%}) subjects in HPV-16/18 vaccine group and the majority (95.7{\%}-97.5{\%}) in HPV-6/11/16/18 vaccine group were seropositive for HPV-16. For HPV-18, the majority (98.1{\%}-100{\%}) of subjects in HPV-16/18 vaccine group were seropositive; however, seropositivity rates in HPV-6/11/16/18 vaccine group decreased considerably (61.1{\%}-76.9{\%}) across the 3 age strata. In the total vaccinated cohort (received ≥ 1 dose regardless of baseline HPV serostatus and DNA status), geometric mean titers for anti-HPV-16 and anti-HPV-18 nAb were higher in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. Based on the 5-y data, piece-wise and modified power-law models predicted a longer durability of nAb response for HPV-16/18 vaccine compared to HPV-6/11/16/18 vaccine. Beyond the differences apparent between the vaccines in terms of immunogenicity and modeled persistence of antibody responses, comparative studies including clinical endpoints would be needed to determine whether differences exist in duration of vaccine-induced protection.",
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