Immunogenicity and safety of an E. coli-produced bivalent human papillomavirus (type 16 and 18) vaccine: A randomized controlled phase 2 clinical trial

Vaccine. 2015 Jul 31;33(32):3940-6. doi: 10.1016/j.vaccine.2015.06.052. Epub 2015 Jun 19.

Abstract

Background: This study aimed to investigate the dosage, immunogenicity and safety profile of a novel human papillomavirus (HPV) types 16 and 18 bivalent vaccine produced by E. coli.

Methods: This randomized, double-blinded, controlled phase 2 trial enrolled women aged 18-25 years in China. Totally 1600 eligible participants were randomized to receive 90μg, 60μg, or 30μg of the recombinant HPV 16/18 bivalent vaccine or the control hepatitis B vaccine on a 0, 1 and 6 month schedule. The designated doses are the combined micrograms of HPV16 and 18 VLPs with dose ratio of 2:1. The immunogenicity of the vaccines was assessed by measuring anti-HPV 16 and 18 neutralizing antibodies and total IgG antibodies. Safety of the vaccine was assessed.

Results: All but one of the seronegative participants who received 3 doses of the HPV vaccines seroconverted at month 7 for anti-HPV 16/18 neutralizing antibodies and IgG antibodies. For HPV 16, the geometric mean titers (GMTs) of the neutralizing antibodies were similar between the 60μg (GMT=10,548) and 90μg (GMT=12,505) HPV vaccine groups and were significantly higher than those in the 30μg (GMT=7596) group. For HPV 18, the GMTs of the neutralizing antibodies were similar among the 3 groups. The HPV vaccine was well tolerated. No vaccine-associated serious adverse events were identified.

Conclusion: The prokaryotic-expressed HPV vaccine is safe and immunogenic in women aged 18-25 years. The 60μg dosage formulation was selected for further investigation for efficacy.

Clinical trials registration: NCT01356823.

Keywords: Human papillomavirus; Immunogenicity; Randomized controlled clinical trial; Safety; Vaccine.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Neutralizing / blood*
  • Antibodies, Viral / blood*
  • China
  • Double-Blind Method
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Escherichia coli / genetics
  • Female
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / immunology*
  • Human papillomavirus 18 / genetics
  • Human papillomavirus 18 / immunology*
  • Humans
  • Immunoglobulin G / blood
  • Papillomavirus Vaccines / administration & dosage
  • Papillomavirus Vaccines / adverse effects*
  • Papillomavirus Vaccines / immunology*
  • Treatment Outcome
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / adverse effects
  • Vaccines, Synthetic / immunology
  • Young Adult

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immunoglobulin G
  • Papillomavirus Vaccines
  • Vaccines, Synthetic

Associated data

  • ClinicalTrials.gov/NCT01356823