title: Serological Correlates of Protection against a GII.4 Norovirus.
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.).
authors.affiliation: Baylor College of Medicine, Houston, Texas, USA ratmar@bcm.edu.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Atmar
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: David I
authors.initials: DI
authors.lastname: Bernstein
authors.affiliation: Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: G Marshall
authors.initials: GM
authors.lastname: Lyon
authors.affiliation: University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Treanor
authors.affiliation: Shin Nippon Biomedical Laboratories, Baltimore, Maryland, USA.
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Al-Ibrahim
authors.affiliation: Baylor College of Medicine, Houston, Texas, USA Michael E. DeBakey VAMC, Houston, Texas, USA.
authors.forename: David Y
authors.initials: DY
authors.lastname: Graham
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Vinjé
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Gregoricus
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Frenck
authors.affiliation: Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Moe
authors.affiliation: University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Wilbur H
authors.initials: WH
authors.lastname: Chen
authors.affiliation: The EMMES Corp., Rockville, Maryland, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ferreira
authors.affiliation: The EMMES Corp., Rockville, Maryland, USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Barrett
authors.affiliation: Baylor College of Medicine, Houston, Texas, USA Michael E. DeBakey VAMC, Houston, Texas, USA.
authors.forename: Antone R
authors.initials: AR
authors.lastname: Opekun
authors.affiliation: Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Estes
authors.affiliation: Takeda Vaccines, Inc., Deerfield, Illinois, USA.
authors.forename: Astrid
authors.initials: A
authors.lastname: Borkowski
authors.affiliation: Takeda Vaccines, Inc., Deerfield, Illinois, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Baehner
authors.affiliation: Takeda Vaccines, Inc., Deerfield, Illinois, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Goodwin
authors.affiliation: Takeda Vaccines, Inc., Deerfield, Illinois, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Edmonds
authors.affiliation: Takeda Vaccines, Inc., Deerfield, Illinois, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Mendelman
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D017250:Caliciviridae Infections / Q000276:immunology / Q000517:prevention & control*; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D029322:Norovirus / Q000276:immunology*; D010919:Placebos / Q000008:administration & dosage; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D010919:Placebos; D058425:Vaccines, Virus-Like Particle; D014765:Viral Vaccines