Preclinical Evaluation of Chicken Egg Yolk Antibody (IgY) Anti-RBD Spike SARS-CoV-2—A Candidate for Passive Immunization against COVID-19

Abstract

The coronavirus disease 2019 (COVID-19) has become a substantial threat to the international health sector and the global economy. As of 26 December 2021, the number of mortalities resulting from COVID-19 exceeded 5.3 million worldwide. The absence of an effective non-vaccine treatment has prompted the quest for prophylactic agents that can be used to combat COVID-19. This study presents the feasibility of chicken egg yolk antibody (IgY) anti-receptor-binding domain (RBD) spike SARS-CoV-2 as a strong candidate to neutralize the virus for application in passive immunization. For the purpose of preclinical studies, we radiolabeled IgY anti-RBD spike SARS-CoV-2 with radionuclide iodine-131. This allowed us to evaluate several biological characteristics of IgY in vitro, in vivo, and ex vivo. The preclinical data suggest that IgY anti-RBD spike SARS-CoV-2 could specifically bind to the SARS-CoV-2 antigens; however, little uptake was observed in normal cells (MRC-5) (<2%). Furthermore, the ex vivo biodistribution study revealed that IgY predominantly accumulated in the trachea of normal mice compared to other organs. We also found that IgY possessed a good safety profile when used as an intranasal agent. Taken together, we propose that IgY anti-RBD spike SARS-CoV-2 has the potential for application in passive immunization against COVID-19.

Novel extraction technologies and potential applications of egg yolk proteins

“…And IgY antibodies exhibited a protective efficacy in prophylaxis and post-infection treatment for SARS-CoV-2. Moreover, the efficiency of specific IgY against SARS-CoV-2 were also reported in other studies (Bao et al, 2022 ; Hakalehto, 2021 ; Lyu et al, 2021 ; Shen et al, 2021 ; Wongso et al, 2022 ). Besides these, Specific IgY antibodies also exhibited an inhibition effect against other virus infections, such as rotavirus (Skrobarczyk et al, 2022 ), influenza (Saczynska et al, 2022 ), human norovirus (Zhu et al, 2019 ), Zika virus (Magalhaes et al, 2022 ) and Ebola virus (Zhang et al, 2021 ), etc.…”

Preclinical Assessment of IgY Antibodies Against Recombinant SARS-CoV-2 RBD Protein for Prophylaxis and Post-Infection Treatment of COVID-19

“…Previous studies have proposed chicken-IgY antibodies as a possible therapeutic agent against COVID-19 disease ( 26 , 36 – 38 ), wherein in vitro and in vivo studies producing IgY against inactivated virus ( 39 ), Spike protein ( 40 – 43 ), or subunit S1 ( 44 ) have demonstrated promising results, using 50 µg of antigen in a three-dose immunization scheme and isolating IgY following the PEG method ( 45 ).…”

Are Hamsters a Suitable Model for Evaluating the Immunogenicity of RBD-Based Anti-COVID-19 Subunit Vaccines?

“…Chickens are not susceptible to Betacoronaviruses, and therefore they can only be used to test the immunogenicity, but not the protective efficacy of the vaccines [ 18 , 40 ]. It was previously reported that the immunization of chickens with inactivated SARS-CoV-2 or S-protein induces specific and neutralizing IgY antibodies with therapeutic potential [ 41 , 42 , 43 ]. The use of chickens to assess the immunogenicity of the RBD is apparently not entirely appropriate.…”