Safety and efficacy of a cytomegalovirus glycoprotein B (gB) vaccine in adolescent girls: A randomized clinical trial

Vaccine. 2016 Jan 12;34(3):313-9. doi: 10.1016/j.vaccine.2015.11.056. Epub 2015 Dec 2.

Abstract

Background: Cytomegalovirus (CMV) is a leading cause of congenital infection and an important target for vaccine development.

Methods: CMV seronegative girls between 12 and 17 years of age received CMV glycoprotein B (gB) vaccine with MF59 or saline placebo at 0, 1 and 6 months. Blood and urine were collected throughout the study for evidence of CMV infection based on PCR and/or seroconversion to non-vaccine CMV antigens.

Results: 402 CMV seronegative subjects were vaccinated (195 vaccine, 207 placebo). The vaccine was generally well tolerated, although local and systemic adverse events were significantly more common in the vaccine group. The vaccine induced gB antibody in all vaccine recipients with a gB geometric mean titer of 13,400 EU; 95%CI 11,436, 15,700, after 3 doses. Overall, 48 CMV infections were detected (21 vaccine, 27 placebo). In the per protocol population (124 vaccine, 125 placebo) vaccine efficacy was 43%; 95%CI: -36; 76, p=0.20. The most significant difference was after 2 doses, administered as per protocol; vaccine efficacy 45%, 95%CI: -9; 72, p=0.08.

Conclusion: The vaccine was safe and immunogenic. Although the efficacy did not reach conventional levels of significance, the results are consistent with a previous study in adult women (Pass et al. N Engl J Med 2009;360:1191) using the same formulation.

Keywords: Adolescent; CMV gB; Cytomegalovirus; Vaccine.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / adverse effects
  • Adolescent
  • Antibodies, Viral / blood
  • Antigens, Viral / analysis
  • Blood / virology
  • Child
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / prevention & control*
  • Cytomegalovirus Vaccines / administration & dosage
  • Cytomegalovirus Vaccines / adverse effects*
  • Cytomegalovirus Vaccines / genetics
  • Cytomegalovirus Vaccines / immunology*
  • DNA, Viral / analysis
  • DNA, Viral / genetics
  • Double-Blind Method
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Female
  • Humans
  • Immunization Schedule
  • Placebos / administration & dosage
  • Polymerase Chain Reaction
  • Polysorbates / administration & dosage
  • Polysorbates / adverse effects
  • Squalene / administration & dosage
  • Squalene / adverse effects
  • Urine / virology
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / adverse effects
  • Vaccines, Subunit / genetics
  • Vaccines, Subunit / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / adverse effects
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Antigens, Viral
  • Cytomegalovirus Vaccines
  • DNA, Viral
  • MF59 oil emulsion
  • Placebos
  • Polysorbates
  • Vaccines, Subunit
  • Vaccines, Synthetic
  • Viral Envelope Proteins
  • glycoprotein B, Simplexvirus
  • Squalene