Feasibility of Polyclonal Avian Immunoglobulins (IgY) as Prophylaxis against Human Norovirus Infection

Background: Human norovirus (HuNoV) is the leading viral cause of diarrhea, with GII.4 as the predominant genotype of HuNoV outbreaks globally. However, new genogroup variants emerge periodically, complicating the development of anti-HuNoV vaccines; other prophylactic or therapeutic medications spec...

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Main Authors: Chad Artman, Nnebuefe Idegwu, Kyle D. Brumfield, Ken Lai, Shirley Hauta, Darryl Falzarano, Viviana Parreño, Lijuan Yuan, James D. Geyer, Julius G. Goepp
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/14/11/2371
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author Chad Artman
Nnebuefe Idegwu
Kyle D. Brumfield
Ken Lai
Shirley Hauta
Darryl Falzarano
Viviana Parreño
Lijuan Yuan
James D. Geyer
Julius G. Goepp
author_facet Chad Artman
Nnebuefe Idegwu
Kyle D. Brumfield
Ken Lai
Shirley Hauta
Darryl Falzarano
Viviana Parreño
Lijuan Yuan
James D. Geyer
Julius G. Goepp
author_sort Chad Artman
collection DOAJ
description Background: Human norovirus (HuNoV) is the leading viral cause of diarrhea, with GII.4 as the predominant genotype of HuNoV outbreaks globally. However, new genogroup variants emerge periodically, complicating the development of anti-HuNoV vaccines; other prophylactic or therapeutic medications specifically for HuNoV disease are lacking. Passive immunization using oral anti-HuNoV antibodies may be a rational alternative. Here, we explore the feasibility of using avian immunoglobulins (IgY) for preventing HuNoV infection in vitro in a human intestinal enteroid (HIE) model. Methods: Hens were immunized with virus-like particles (VLP) of a GII.4 HuNoV strain (GII.4/CHDC2094/1974/US) by intramuscular injection. The resulting IgY was evaluated for inhibition of binding to histo-blood group antigens (HBGA) and viral neutralization against representative GII.4 and GII.6 clinical isolates, using an HIE model. Results: IgY titers were detected by three weeks following initial immunization, persisting at levels of 1:2<sup>21</sup> (1:2,097,152) from 9 weeks to 23 weeks. Anti-HuNoV IgY significantly (<i>p</i> < 0.05) blocked VLP adhesion to HBGA up to 1:12,048 dilution (0.005 mg/mL), and significantly (<i>p</i> < 0.05) inhibited replication of HuNoV GII.4[P16] Sydney 2012 in HIEs up to 1:128 dilution (0.08 mg/mL). Neutralization was not detected against genotype GII.6. Conclusions: We demonstrate the feasibility of IgY for preventing infection of HIE by HuNoV GII.4. Clinical preparations should cover multiple circulating HuNoV genotypes for comprehensive effects. Plans for animal studies are underway.
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spelling doaj.art-8e5598578c484bbe84e126d38e9dc0842023-11-24T07:16:08ZengMDPI AGViruses1999-49152022-10-011411237110.3390/v14112371Feasibility of Polyclonal Avian Immunoglobulins (IgY) as Prophylaxis against Human Norovirus InfectionChad Artman0Nnebuefe Idegwu1Kyle D. Brumfield2Ken Lai3Shirley Hauta4Darryl Falzarano5Viviana Parreño6Lijuan Yuan7James D. Geyer8Julius G. Goepp9Scaled Microbiomics, LLC, Hagerstown, MD 21740, USAScaled Microbiomics, LLC, Hagerstown, MD 21740, USAMaryland Pathogen Research Institute, University of Maryland, College Park Campus, College Park, MD 20742, USAVaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK S7N 5E3, CanadaVaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK S7N 5E3, CanadaVaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK S7N 5E3, CanadaDepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USADepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USAInstitute for Rural Health Research, College of Community Health Science, University of Alabama, Tuscaloosa, AL 35487, USAScaled Microbiomics, LLC, Hagerstown, MD 21740, USABackground: Human norovirus (HuNoV) is the leading viral cause of diarrhea, with GII.4 as the predominant genotype of HuNoV outbreaks globally. However, new genogroup variants emerge periodically, complicating the development of anti-HuNoV vaccines; other prophylactic or therapeutic medications specifically for HuNoV disease are lacking. Passive immunization using oral anti-HuNoV antibodies may be a rational alternative. Here, we explore the feasibility of using avian immunoglobulins (IgY) for preventing HuNoV infection in vitro in a human intestinal enteroid (HIE) model. Methods: Hens were immunized with virus-like particles (VLP) of a GII.4 HuNoV strain (GII.4/CHDC2094/1974/US) by intramuscular injection. The resulting IgY was evaluated for inhibition of binding to histo-blood group antigens (HBGA) and viral neutralization against representative GII.4 and GII.6 clinical isolates, using an HIE model. Results: IgY titers were detected by three weeks following initial immunization, persisting at levels of 1:2<sup>21</sup> (1:2,097,152) from 9 weeks to 23 weeks. Anti-HuNoV IgY significantly (<i>p</i> < 0.05) blocked VLP adhesion to HBGA up to 1:12,048 dilution (0.005 mg/mL), and significantly (<i>p</i> < 0.05) inhibited replication of HuNoV GII.4[P16] Sydney 2012 in HIEs up to 1:128 dilution (0.08 mg/mL). Neutralization was not detected against genotype GII.6. Conclusions: We demonstrate the feasibility of IgY for preventing infection of HIE by HuNoV GII.4. Clinical preparations should cover multiple circulating HuNoV genotypes for comprehensive effects. Plans for animal studies are underway.https://www.mdpi.com/1999-4915/14/11/2371outbreak prevention and controlnoroviruscalicivirusfoodborne diseasegastroenteritis outbreaksIgY
spellingShingle Chad Artman
Nnebuefe Idegwu
Kyle D. Brumfield
Ken Lai
Shirley Hauta
Darryl Falzarano
Viviana Parreño
Lijuan Yuan
James D. Geyer
Julius G. Goepp
Feasibility of Polyclonal Avian Immunoglobulins (IgY) as Prophylaxis against Human Norovirus Infection
Viruses
outbreak prevention and control
norovirus
calicivirus
foodborne disease
gastroenteritis outbreaks
IgY
title Feasibility of Polyclonal Avian Immunoglobulins (IgY) as Prophylaxis against Human Norovirus Infection
title_full Feasibility of Polyclonal Avian Immunoglobulins (IgY) as Prophylaxis against Human Norovirus Infection
title_fullStr Feasibility of Polyclonal Avian Immunoglobulins (IgY) as Prophylaxis against Human Norovirus Infection
title_full_unstemmed Feasibility of Polyclonal Avian Immunoglobulins (IgY) as Prophylaxis against Human Norovirus Infection
title_short Feasibility of Polyclonal Avian Immunoglobulins (IgY) as Prophylaxis against Human Norovirus Infection
title_sort feasibility of polyclonal avian immunoglobulins igy as prophylaxis against human norovirus infection
topic outbreak prevention and control
norovirus
calicivirus
foodborne disease
gastroenteritis outbreaks
IgY
url https://www.mdpi.com/1999-4915/14/11/2371
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