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. 2022 Oct 27;14(11):2371.
doi: 10.3390/v14112371.

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

Chad Artman  1 , Nnebuefe Idegwu  1 , Kyle D Brumfield  2   3 , Ken Lai  4 , Shirley Hauta  4 , Darryl Falzarano  4   5 , Viviana Parreño  6   7 , Lijuan Yuan  6 , James D Geyer  8 , Julius G Goepp  1
Affiliations

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

Chad Artman et al. Viruses. .

Abstract

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 1:221 (1:2,097,152) from 9 weeks to 23 weeks. Anti-HuNoV IgY significantly (p < 0.05) blocked VLP adhesion to HBGA up to 1:12,048 dilution (0.005 mg/mL), and significantly (p < 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.

Keywords: IgY; calicivirus; foodborne disease; gastroenteritis outbreaks; norovirus; outbreak prevention and control; passive immunotherapy.

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Conflict of interest statement

With the exception of the contractual support furnished by the US National Institute for Allergy and Infectious Diseases (NIAID; Contract No. HHSN-2722017-00038I), this project was funded entirely by Scaled Microbiomics, LLC, which holds a pending patent on the use of IgY in the prophylaxis and treatment of Human Norovirus and Enterotoxigenic E. coli infection. Authors CA, NI, and JG were employees of Scaled Microbiomics at the time this work was carried out. The authors and Scaled Microbiomics declare that they have no competing interests.

Figures

Figure 1
Figure 1
Box and whisker plots of inhibition of HuNoVLP adhesion to HBGA antigens in a cell-free system. Boxes represent interquartile range (IQR) with median, shown as center bar of each sample group (N = 3 replicates per group). Whiskers represent 1.5 times the IQR. p-value, by two-sample t-test method, and 95% confidence interval (CI) was calculated using R software package EnvStats (v.2.3.1) [28]. (ns), not significant, p > 0.05; (**), p ≤ 0.01; (***), p ≤ 0.001; (****), p ≤ 0.0001.
Figure 2
Figure 2
Comparison of neutralization activities of immunized (HuNoVLP IgY) and unimmunized IgY against two isolates (A) AB2 and (B) 3241SK of HuNoV GII.4 in J2 HIE cells (geometric mean with 95% confidence intervals) showing pooled results of two independent experiments (N = 8 total replicates per treatment condition). Antibodies were prepared in serial 2-fold dilutions. 2-CMC (2′-C-methylcytidine), a small-molecule viral polymerase inhibitor [39] was used as a positive drug control and tested at a concentration of 200 µM. NTC: Non-treatment control for virus growth in the cells (medium alone + virus). Dashed line indicates RT-qPCR limit of detection (2 × 102 genome copies per reaction).
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