Serological Correlates of Protection against a GII.4 Norovirus

Clin Vaccine Immunol. 2015 Aug;22(8):923-9. doi: 10.1128/CVI.00196-15. Epub 2015 Jun 3.

Abstract

Noroviruses are the leading cause of acute gastroenteritis worldwide, and norovirus vaccine prevention strategies are under evaluation. The immunogenicity of two doses of bivalent genogroup 1 genotype 1 (GI.1)/GII.4 (50 μg of virus-like particles [VLPs] of each strain adjuvanted with aluminum hydroxide and 3-O-desacyl-4'monophosphoryl lipid A [MPL]) norovirus vaccine administered to healthy adults in a phase 1/2 double-blind placebo-controlled trial was determined using virus-specific serum total antibody enzyme-linked immunosorbent assay (ELISA), IgG, IgA, and histoblood group antigen (HBGA)-blocking assays. Trial participants subsequently received an oral live virus challenge with a GII.4 strain, and the vaccine efficacy results were reported previously (D. I. Bernstein et al., J Infect Dis 211:870-878, 2014, doi:10.1093/infdis/jiu497). This report assesses the impact of prechallenge serum antibody levels on infection and illness outcomes. Serum antibody responses were observed in vaccine recipients by all antibody assays, with first-dose seroresponse frequencies ranging from 88 to 100% for the GI.1 antigen and from 69 to 84% for the GII.4 antigen. There was little increase in antibody levels after the second vaccine dose. Among the subjects receiving the placebo, higher prechallenge serum anti-GII.4 HBGA-blocking and IgA antibody levels, but not IgG or total antibody levels, were associated with a lower frequency of virus infection and associated illness. Notably, some placebo subjects without measurable serum antibody levels prechallenge did not become infected after norovirus challenge. In vaccinees, anti-GII.4 HBGA-blocking antibody levels of >1:500 were associated with a lower frequency of moderate-to-severe vomiting or diarrheal illness. In this study, prechallenge serum HBGA antibody titers correlated with protection in subjects receiving the placebo; however, other factors may impact the likelihood of infection and illness after virus exposure. (This study is registered at ClinicalTrials.gov under registration number NCT1609257.).

Trial registration: ClinicalTrials.gov NCT01609257.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / blood*
  • Biomarkers / blood*
  • Caliciviridae Infections / immunology
  • Caliciviridae Infections / prevention & control*
  • Double-Blind Method
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin G / blood
  • Male
  • Middle Aged
  • Norovirus / immunology*
  • Placebos / administration & dosage
  • Vaccines, Virus-Like Particle / administration & dosage
  • Vaccines, Virus-Like Particle / immunology*
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / immunology*
  • Young Adult

Substances

  • Antibodies, Viral
  • Biomarkers
  • Immunoglobulin A
  • Immunoglobulin G
  • Placebos
  • Vaccines, Virus-Like Particle
  • Viral Vaccines

Associated data

  • ClinicalTrials.gov/NCT01609257