학술논문
Serological Correlates of Protection against a GII.4 Norovirus
Document Type
Article
Author
Atmar, Robert L.; Bernstein, David I.; Lyon, G. Marshall; Treanor, John J.; Al-Ibrahim, Mohamed S.; Graham, David Y.; Vinjé, Jan; Jiang, Xi; Gregoricus, Nicole; Frenck, Robert W.; Moe, Christine L.; Chen, Wilbur H.; Ferreira, Jennifer; Barrett, Jill; Opekun, Antone R.; Estes, Mary K.; Borkowski, Astrid; Baehner, Frank; Goodwin, Robert; Edmonds, Anthony; Mendelman, Paul M.
Source
Clinical and Vaccine Immunology (formerly CDLI); June 2015, Vol. 22 Issue: 8 p923-929, 7p
Subject
Language
ISSN
15566811; 1556679X
Abstract
ABSTRACTNoroviruses 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.)