Serological Correlates of Protection against a GII.4 Norovirus

American Society for Microbiology - Tập 22 Số 8 - Trang 923-929 - 2015
Robert L. Atmar1, David I. Bernstein2, G. Marshall Lyon3, John J. Treanor4, Mohamed S. Al-Ibrahim5, David Y. Graham6,7, Jan Vinjé8, Xi Jiang2, Nicole Gregoricus8, Robert W. Frenck2, Christine L. Moe9, Wilbur H. Chen10, Jennifer Ferreira11, Jill Barrett11, Antone R. Opekun6,7, Mary K. Estes1, Astrid Borkowski12, Frank Baehner12, Robert R. Goodwin12, Anthony Edmonds12, Paul M. Mendelman12
1Baylor College of Medicine, Houston, Texas - USA
2Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA.
3Emory University School of Medicine, Atlanta, Georgia USA
4University of Rochester Medical Center , Rochester, New York, USA
5Shin Nippon Biomedical Laboratories, Baltimore, Maryland, USA.
6Michael E. DeBakey VAMC, Houston, Texas, USA
7aBaylor College of Medicine, Houston, Texas, USA
8Centers for Disease Control and Prevention, Atlanta, Georgia, USA
9Rollins School of Public Health Emory University, Atlanta, Georgia, USA
10University of Maryland School of Medicine, Baltimore, Maryland, USA.
11The EMMES Corp., Rockville, Maryland, USA.
12Takeda Vaccines, Inc., Deerfield, Illinois, USA

Tóm tắt

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.)

Từ khóa


Tài liệu tham khảo

10.1097/MOG.0000000000000022

10.3201/eid1908.130465

10.1056/NEJMsa1206589

10.1016/j.vaccine.2012.09.040

Green KY. 2013. Caliciviridae: The noroviruses, p 582–608. In Knipe DM, Howley PM (ed), Fields virology. Lippincott Williams & Wilkins, Philadelphia, PA.

10.1007/s00705-013-1708-5

10.1086/605127

10.1093/cid/cis372

10.1128/JVI.00674-07

10.1093/infdis/jit370

10.1086/656364

10.1056/NEJMoa1101245

10.1128/CVI.05592-11

10.1093/infdis/jiu497

10.1016/j.vaccine.2012.03.050

10.1093/infdis/170.1.34

10.1093/infdis/jiu337

10.1128/CVI.00039-11

10.1208/aapsj0902029

10.1016/j.tim.2004.04.005

10.1371/journal.ppat.1000983

10.1002/rmv.1757

10.1038/nm860

10.1002/jmv.20423

10.1128/JVI.79.24.15351-15355.2005

10.1007/s12560-010-9038-1

10.1093/infdis/jis514

10.1099/vir.0.19478-0

Herbst-Kralovetz MM, Radtke AL, Lay MK, Hjelm BE, Bolick AN, Sarker SS, Atmar RL, Kingsley DH, Arntzen CJ, Estes MK, Nickerson CA. 2013. Lack of norovirus replication and histo-blood group antigen expression in 3-dimensional intestinal epithelial cells. Emerg Infect Dis 19:421–428.

10.1016/j.virol.2010.07.001

10.1128/JVI.79.11.6714-6722.2005

10.1128/JVI.00802-08

10.1016/j.vaccine.2006.03.080

10.1086/522428

10.1093/infdis/jir661

10.1111/j.1472-765X.2005.01775.x

10.1093/infdis/jiv053

Thông tin
Thông tin xuất bản

American Society for Microbiology

Tập 22 Số 8

923-929

Thông tin tác giả