Antigenic Relatedness of Norovirus GII.4 Variants Determined by Human Challenge Sera.
The GII.4 noroviruses (NoVs) are a single genotype that is responsible for over 50% of NoV gastroenteritis epidemics worldwide. However, GII.4 NoVs have been found to undergo antigenic drifts, likely selected by host herd immunity, which raises an issue for vaccine strategies against NoVs. We previously characterized GII.4 NoV antigenic variations and found significant levels of antigenic relatedness among different GII.4 variants. Further characterization of the genetic and antigenic relatedness of recent GII.4 variants (2008b and 2010 cluster) was performed in this study. The amino acid sequences of the receptor binding interfaces were highly conserved among all GII.4 variants from the past two decades. Using serum samples from patients enrolled in a GII.4 virus challenge study, significant cross-reactivity between major GII.4 variants from 1998 to 2012 was observed using enzyme-linked immunosorbent assays and HBGA receptor blocking assays. The overall abilities of GII.4 NoVs to bind to the A/B/H HBGAs were maintained while their binding affinities to individual ABH antigens varied. These results highlight the importance of human HBGAs in NoV evolution and how conserved antigenic types impact vaccine development against GII.4 variants.
Department of Epidemiology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, China; Divisions of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
Ying-Chun
YC
Dai
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China; Divisions of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
Xu-Fu
XF
Zhang
Divisions of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
Ming
M
Xia
Divisions of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.
Ming
M
Tan
Divisions of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
Christina
C
Quigley
Divisions of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
Wen
W
Lei
Divisions of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
Hao
H
Fang
Divisions of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
Weiming
W
Zhong
Provincial Laboratory for Public Health (ProvLab), Edmonton, Alberta, Canada; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton,Alberta, Canada.
Bonita
B
Lee
Provincial Laboratory for Public Health (ProvLab), Edmonton, Alberta, Canada; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton,Alberta, Canada.
Xiaoli
X
Pang
Department of Epidemiology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, China.
Jun
J
Nie
Divisions of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.
Xi
X
Jiang
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001789:Blood Group Antigens / Q000737:chemistry / Q000378:metabolism*; D017250:Caliciviridae Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005759:Gastroenteritis / Q000097:blood / Q000276:immunology* / Q000821:virology; D014644:Genetic Variation; D006801:Humans; D007106:Immune Sera / Q000378:metabolism*; D051379:Mice; D029322:Norovirus / Q000145:classification / Q000235:genetics / Q000276:immunology*
D000956:Antigens, Viral; D001789:Blood Group Antigens; D007106:Immune Sera