Chicken Egg Yolk Antibodies (IgYs) block the binding of multiple SARS-CoV-2 spike protein variants to human ACE2

Wei, Shitong; Duan, Suqing; Liu, Xiaomei; Wang, Hongmei; Ding, Shaohua; Chen, Yezhou; Xie, Jinxing; Tian, Jingjing; Yu, N. T.; Ge, Pingju; Zhang, xinglin; Chen, Xiaohong; Li, Yong; Meng, Qinglin

doi:10.1016/j.intimp.2020.107172

Cited by 29 publications

(17 citation statements)

References 10 publications

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“…Although the great potential of chicken IgY for COVID‐19 has been proposed by several labs (Lu et al, 2020 ; Shen et al, 2021 ; Wei et al, 2021 ), to our knowledge, the affinity of IgY to antigens has not been reported yet. Most current anti‐SARS‐CoV‐2 antibodies neutralize viruses by binding to epitopes on the S protein of SARS‐CoV‐2 (Tai et al, 2020 ; Tian et al, 2020 ).…”

Section: Discussionmentioning

confidence: 90%

“…Till now, several studies have been carried out on the potential anti‐SARS‐CoV‐2 effect of IgY (Lu et al, 2020 ; Shen et al, 2021 ; Wei et al, 2021 ). IgY targeting the full‐length S protein, S1 subunit or RBD were produced, and all studies showed a high titer and variable neutralizing activity against SARS‐CoV‐2.…”

Section: Discussionmentioning

confidence: 99%

“…Compared with the previously reported monoclonal antibodies (IC 50 ranged from 0.03 to 50 μg ml −1 ; Brouwer et al, 2020 ; Chi et al, 2020 ; Ju et al, 2020 ), the IC 50 value of S1‐IgY in our study was relatively high (IC 50 : 0.99 mg ml −1 ), which may be attributed to the fact that the specific IgY only accounts for 1%–10% of the total IgY antibodies (Michael et al, 2010 ). Interestingly, IgY targeting the S1 protein has been previously found to be able to competitively bind to six SARS‐CoV‐2 spike protein mutants (Wei et al, 2021 ). Moreover, epitope mapping revealed that two of five linear epitopes of IgY‐S (IgY targeting S protein) in SARS‐CoV‐2 S were cross‐reactive with SARS‐CoV S (Lu et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

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Egg yolk immunoglobulin (IgY) targeting SARS-CoV-2 S1 as potential virus entry blocker

Bao

Zhang

Lyu

et al. 2022

Journal of Applied Microbiology

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Aims COVID‐19 pandemic caused by SARS‐CoV‐2 has become a public health crisis worldwide. In this study, we aimed at demonstrating the neutralizing potential of the IgY produced after immunizing chicken with a recombinant SARS‐CoV‐2 spike protein S1 subunit. Methods and Results E . coli BL21 carrying plasmid p ET28a‐S1 was induced with IPTG for the expression of SARS‐CoV‐2 S1 protein. The recombinant His‐tagged S1 was purified and verified by SDS‐PAGE, Western blot and biolayer interferometry (BLI) assay. Then S1 protein emulsified with Freund's adjuvant was used to immunize layer chickens. Specific IgY against S1 (S1‐IgY) produced from egg yolks of these chickens exhibited a high titer (1:25,600) and a strong binding affinity to S1 ( K D = 318 nmol L −1 ). The neutralizing ability of S1‐IgY was quantified by a SARS‐CoV‐2 pseudotyped virus‐based neutralization assay with an IC 50 value of 0.99 mg ml −1 . In addition, S1‐IgY exhibited a strong ability in blocking the binding of SARS‐CoV‐2 S1 to hACE2, and it could partially compete with hACE2 for the binding sites on S1 by BLI assays. Conclusions We demonstrated here that after immunization of chickens with our recombinant S1 protein, IgY neutralizing antibodies were generated against the SARS‐CoV‐2 spike protein S1 subunit; therefore, showing the potential use of IgY to block the entry of this virus. Significance and Impact of the Study IgY targeting S1 subunit of SARS‐CoV‐2 could be a promising candidate for pre‐ and post‐exposure prophylaxis or treatment of COVID‐19. Administration of IgY‐based oral preparation, oral or nasal spray may have profound implications for blocking SARS‐CoV‐2.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Egg yolk immunoglobulin (IgY) targeting SARS-CoV-2 S1 as potential virus entry blocker

Bao

Zhang

Lyu

et al. 2022

Journal of Applied Microbiology

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“…Intranasal antibody prophylaxis is an especially effective means against multiple viral pathogens ( 29 – 32 ). Further, key characteristics of the mechanism of action of anti-SARS- CoV-2 IgY may be ideal for effective transient immunization while awaiting global COVID-19 vaccination: a) anti-spike-S1 IgY can neutralize or bind SARS-CoV-2 in vitro ( 33 – 35 ), b) superficially administered anti-SARS-CoV-2 IgY may bind to the spike protein on the surface of the virus, competing with the binding of the viral spike protein to the human angiotensin-converting enzyme 2 receptor to prevent cell entry and infection, c) anti-SARS-CoV-2 IgY may also agglutinate SARS-CoV-2 on the surface of the mucosa, thus preventing viral lateral motility and entry across the mucosa, and d) intranasal administration can deliver anti-SARS-CoV-2 IgY to the nasal passage and throat mucosa (through mucociliary clearance), the main routes of viral entry and replication. This approach may be especially valuable for immediate and short-lived protection in health care and other at-risk service workers in regions where new variants of SARS-CoV-2 may evade immunity produced by vaccines or where COVID-19 vaccination is unavailable.…”

Section: Diagnosis and Treatment Of Viral Infectionsmentioning

confidence: 99%

Immunoglobulin Y for Potential Diagnostic and Therapeutic Applications in Infectious Diseases

et al. 2021

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Antiviral, antibacterial, and antiparasitic drugs and vaccines are essential to maintaining the health of humans and animals. Yet, their production can be slow and expensive, and efficacy lost once pathogens mount resistance. Chicken immunoglobulin Y (IgY) is a highly conserved homolog of human immunoglobulin G (IgG) that has shown benefits and a favorable safety profile, primarily in animal models of human infectious diseases. IgY is fast-acting, easy to produce, and low cost. IgY antibodies can readily be generated in large quantities with minimal environmental harm or infrastructure investment by using egg-laying hens. We summarize a variety of IgY uses, focusing on their potential for the detection, prevention, and treatment of human and animal infections.

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“…It is currently used as an antigen for serological test kits, and as an immunogen. RBD could be used to produce neutralizing antibodies at large scale in animal systems such as egg yolk (IgY) 13,14 or in horses 15 .…”

Section: Introductionmentioning

confidence: 99%

Production of a Highly Immunogenic Antigen from SARS-CoV-2 by Covalent Coupling of the Receptor Binding Domain of Spike Protein to a Multimeric Carrier

Berguer¹,

Blaustein²,

Bredeston³

et al. 2021

Preprint

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Since the discovery of SARS-CoV-2, several antigens have been proposed to be part of COVID-19 vaccines. The receptor binding domain (RBD) of Spike protein is one of the promising candidates to develop effective vaccines since it can induce potent neutralizing antibodies. We previously reported the production of RBD in Pichia pastoris and showed it is structurally identical to the protein produced in mammalian HEK-293T cells. In this work we designed an RBD multimer construct with the purpose of increasing RBD immunogenicity. We produced multimeric particles by a transpeptidation reaction between the RBD expressed in P. pastoris and Lumazine Synthase from Brucella abortus (BLS), which is a highly immunogenic and very stable decameric protein of 170 kDa. We vaccinated mice with two doses 30 days apart, and then we measured humoral immune response. When the number of RBD copies coupled to BLS was high (6-7 RBD molecules per BLS decamer, in average), the immune response was significantly better than that elicited by RBD alone or even by RBD-BLS comprising low number of RBD copies (1-2 RBD molecules per BLS decamer). Remarkably, the construct with high number of RBD copies induced high IgG titers with high neutralizing capacity. Furthermore, a superior immune response was observed when Al(OH)3 adjuvant was added to this formulation, exhibiting a higher titer of neutralizing antibodies. Altogether our results suggest that RBD covalent coupled to BLS forming a multimer-particle shows an advantageous architecture to the antigen-presentation to the immune system which enhances immune responses. This new antigen should be considered a potent candidate for a protein-based vaccine.

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Chicken Egg Yolk Antibodies (IgYs) block the binding of multiple SARS-CoV-2 spike protein variants to human ACE2

Cited by 29 publications

References 10 publications

Egg yolk immunoglobulin (IgY) targeting SARS-CoV-2 S1 as potential virus entry blocker

Egg yolk immunoglobulin (IgY) targeting SARS-CoV-2 S1 as potential virus entry blocker

Immunoglobulin Y for Potential Diagnostic and Therapeutic Applications in Infectious Diseases

Production of a Highly Immunogenic Antigen from SARS-CoV-2 by Covalent Coupling of the Receptor Binding Domain of Spike Protein to a Multimeric Carrier

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