Egg Yolk Antibody IgY for COVID-19

This article discusses the potential use of IgY antibodies from chicken eggs to prevent and treat COVID-19.

Human mothers protect their infants from infections by giving them antibodies thru breast milk. Chickens protect their future chicks by producing antibodies in the eggs’ yolk.

In 1893, Emil Klemperer reported that egg yolk antibodies could neutralize tetanus antitoxin. For almost 100 years, no advancement was made with IgY until the 1980s, when the use of reagents to process IgY was developed.

IgY has several advantages over IgG from other animals. The amount of antibodies a hen can produce is comparable to much larger animals like a goat or sheep. Another reason is the cheaper maintenance cost of chickens than mice and rabbits.[7]

IgY is more resistant to degradation and fragmentation. The half-life of IgY is of months, and it can retain activity for up to six months at room temperature and one month at 37ºC. In certain forms, it can last up to five years at 4ºC.

Compare that to the Pfizer mRNA shot that has to be stored between -90°C and -60°C (-130°F and -76°F) until the expiration date.

Animal and Human uses of IgY

In China, IgY has been approved to treat goose plague, duck plague, and other diseases, according to the China Veterinary Pharmacopoeia.[2]

A study from Argentina showed that Egg yolk IgY effectively prevented rotavirus-induced diarrhea in newborn calves.

IgY has been used in Middle East respiratory syndrome (MERS), rotavirus,influenza, Zika, dengue, Ebola, and the SARS virus.

Passive vs. Active Immunity

IgY is used for passive immunity. In contrast to active immunity, where the vaccinee makes the immune response or antibodies, passive immunity introduces antibodies to the recipient.

IgY and COVID-19

As early as Nov 2020, Wei et al. showed that anti-spike Egg Yolk Antibodies (IgY) could prevent the attachment of SARS-CoV-2 spike proteins with different mutations to human ACE2 receptors.

The study was significant because it showed that the IgY could be effective against other variants of concern.

Their study was verified by Frumkin et al., who inoculated chickens with the ancestral SARS-CoV-2 variant. To their surprise, the IgY produced by the chickens neutralized the other variants, namely the D614G, Alpha, Beta, Delta, and Omicron, using in vitro studies.

IgY for different parts of the SARS-CoV-2

SARS-CoV-2 has two main parts. The nucleocapsid is in the middle, and the spike proteins stick out. The spike protein is divided into the S1, the S1-Receptor-Binding Domain (RBD), and the S2 protein.

Ravlo et al. injected hens twice 14 days apart with a purified segment of the SARS-CoV-2 RBD. They found that the IgY neutralized the viral RBD of the Wuhan and Omicron variants.

The IgY also decreased the SARS-CoV-2 replication in the lungs of Syrian Golden Hamsters. Syrian golden hamsters are the nearest animals that can mimic the human response to SARS-CoV-2.

Additionally, the IgY did not hamper the development of an adaptive immune system to the virus.[2]

In contrast, Paxlovid prevents the development of the adaptive immune response against SARS-CoV-2.— Paxlovid blunts adaptive immune response to SARS-CoV-2

This explains the result of The Paxlovid Rebound Study.

IgY Human clinical trials

A double-blind, randomized, placebo-controlled phase 1 study was done by Frumkin et al. in 48 healthy adults.[3]

Phase 1 studies assessed the safety, tolerability, and pharmacokinetics of the anti-SARS-CoV-2 IgY and were not designed to evaluate efficacy. Pharmacokinetics is the study of how the body interacts with a substance.

The study introduced IgY into the nose of human subjects. The most frequent treatment-emergent adverse event was a headache, with similar rates between placebo (17%) and anti-SARS-CoV-2 RBD IgY (14%).

All adverse events were mild in severity. There was no nasal irritation or congestion.

The Phase 1 results are encouraging. The IgY did not enter the nose lining, and the human subjects did not develop anti-IgY antibodies.

No participant receiving intranasal anti-SARS-CoV-2 IgY in the multiple-dose phase had measurable levels of anti-SARS-CoV-2 RBD IgY in their sera, reflecting the absence of systemic absorption of topically administered IgY following intranasal application.

We also found no evidence of a systemic inflammatory immune response triggered by the topical treatment with anti-SARS-CoV-2 RBD IgY in humans, and no detectable increase in 80 sera cytokines.

In the study by Frumkin et al., they did not successfully prevent diseases in Syrian golden hamsters using their IgY. Their reason was that the SARS-CoV-2 dose was too high, and some viruses probably escaped the IgY and went into the lungs.[3]

In the study published by Yeh et al. in November 2022. They showed that the IgY effectively prevented disease in the golden hamsters before or after a SARS-CoV-2 infection. Moreover, the IgY could neutralize the S1, S1-RBD, and S2 protein subunits.[5]

Saputri et al. showed that the IgY could neutralize the SARS-CoV-2 nucleocapsid antigen on top of the S1 and RBD.[9]

Who can benefit from Passive IgY Immunity in Humans?

Since IgY can bind to the S1, S1-RBD, S2, and nucleocapsid of the SARS-CoV-2, it can neutralize the virus and prevent COVID-19.

Egg IgY does not produce antibody-dependent enhancement.[4] That’s because IgY does not activate the complement system.[8]

Immune imprinting is when the immune system generates an immune response against the original virus strain it encountered. For example, COVID shots given to the elderly develop antibodies effective against the endemic coronaviruses they met before the Wuhan strain. That is why older people can still get COVID even though they are “vaccinated.”

What is Immune Imprinting and why it is good to know

IgY may be helpful for the elderly since the IgY will block the entry of SARS-CoV-2 into the cells and prevent infection.

People who are immune compromised, like those with diabetes, and take immune suppressant drugs may not generate the right amount of antibodies and T cells when vaccinated.

IgY does not attach to the rheumatoid factor in humans and makes autoimmunity far less likely.[8] This makes IgY ideal for the younger age group and women since they are prone to autoantibody formation. For example, younger people are more prone to myocarditis after the COVID shots.

Autoimmune conditions after COVID-19 and its injections

IgY is inexpensive to produce

Another advantage of using IgY is its cheap production. IgY generation is inexpensive and fast; one egg of an SPF hen produces 20-80 daily doses (at 6 mg/dose) within three weeks from the first injection (1 week after the first boost).[3]. SPF hens are specially bred chickens that are free of pathogens.

Saputri et al. used Hy-Line Brown hens in their study.[9]

Carrie Chen and her group from Stanford University developed a method to extract and purify IgY antibodies from egg yolks of hens immunized against viral pathogens.[6]

They used a home food processor with a 3D-printed adapter to enable IgY precipitation. Gel electrophoresis and Western blot analyses confirmed that the method produced highly enriched IgY preparation. Each commercial egg produced ~ 90 mg of IgY.

The kit that they produce costs them US$584.36. The cost of 100 hens plus housing was US$826.00. Total kit + non-disposable + hens = US$1656.95.

The cost per dose (/2500) was US$0.66. Those were 2022 UD dollars.

It does sound exciting. Chen et al. said chickens could be immunized by injection in poultry farms with recombinant viruses so they are not infectious.

Chickens are not susceptible to SARS-CoV-2. A study by Schlottau et al. proved that.[10]

Using IgYs in aerosol or spray formulations on the respiratory tract, the oral cavity, and even the digestive tract may be a worthwhile strategy to prevent SARS-CoV-2 and coming pandemics.[1]

It is curious to know if the potential of egg yolk IgY to prevent COVID-19 and other viral infections has something to do with several poultry farms getting burned since 2021.

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References:

Wei S, Duan S, Liu X, Wang H, Ding S, Chen Y, Xie J, Tian J, Yu N, Ge P, Zhang X, Chen X, Li Y, Meng Q. Chicken Egg Yolk Antibodies (IgYs) block the binding of multiple SARS-CoV-2 spike protein variants to human ACE2. Int Immunopharmacol. 2021 Jan;90:107172. doi: 10.1016/j.intimp.2020.107172. Epub 2020 Nov 3. PMID: 33191178; PMCID: PMC7608017.
Ravlo E, Evensen L, Sanson G, Hildonen S, Ianevski A, Skjervold PO, Ji P, Wang W, Kaarbø M, Kaynova GD, Kainov DE, Bjørås M. Antiviral Immunoglobulins of Chicken Egg Yolk for Potential Prevention of SARS-CoV-2 Infection. Viruses. 2022 Sep 26;14(10):2121. doi: 10.3390/v14102121. PMID: 36298676; PMCID: PMC9609661.
Frumkin L.R., Lucas M., Scribner C.L., Ortega-Heinly N., Rogers J., Yin G., Hallam T.J., Yam A., Bedard K., Begley R., et al. Egg-Derived Anti-SARS-CoV-2 Immunoglobulin Y (IgY) With Broad Variant Activity as Intranasal Prophylaxis Against COVID-19. Front. Immunol. 2022;13:899617. doi: 10.3389/fimmu.2022.899617.
Carlander D., Stalberg J., Larsson A. Chicken antibodies: A clinical chemistry perspective. Ups. J. Med. Sci. 1999;104:179–189. doi: 10.3109/03009739909178961.
Yeh CT, Lee CY, Ho YJ, Chen SA, Chen LY, Liu PC, Chin YF, Chen AY, Hsieh PS, Hung YJ, Chen CC, Wang YC, Lee GC. Immunoglobulin Y Specific for SARS-CoV-2 Spike Protein Subunits Effectively Neutralizes SARS-CoV-2 Infectivity and Ameliorates Disease Manifestations In Vivo. Biomedicines. 2022 Nov 1;10(11):2774. doi: 10.3390/biomedicines10112774. PMID: 36359294; PMCID: PMC9687769.
Chen CJ, Hudson AF, Jia AS, Kunchur CR, Song AJ, Tran E, Fisher CJ, Zanchi D, Lee L, Kargotich S, Romeo M, Koperniku A, Pamnani RD, Mochly-Rosen D. Affordable IgY-based antiviral prophylaxis for resource-limited settings to address epidemic and pandemic risks. J Glob Health. 2022 Feb 26;12:05009. doi: 10.7189/jogh.12.05009. PMID: 35265332; PMCID: PMC8877785.
Pereira EPV, van Tilburg MF, Florean EOPT, Guedes MIF. Egg yolk antibodies (IgY) and their applications in human and veterinary health: A review. Int Immunopharmacol. 2019 Aug;73:293-303. doi: 10.1016/j.intimp.2019.05.015. Epub 2019 May 22. PMID: 31128529; PMCID: PMC7106195.
León-Núñez D, Vizcaíno-López MF, Escorcia M, Correa D, Pérez-Hernández E, Gómez-Chávez F. IgY Antibodies as Biotherapeutics in Biomedicine. Antibodies (Basel). 2022 Sep 29;11(4):62. doi: 10.3390/antib11040062. PMID: 36278615; PMCID: PMC9590010.
Eka Saputri M, Aisyah Rahmalia Effendi S, Nadila R, Azzam Fajar S, Damajanti Soejoedono R, Handharyani E, Nadia Poetri O. Immunoglobulin yolk targeting spike 1, receptor binding domain of spike glycoprotein and nucleocapsid of SARS-CoV-2 blocking RBD-ACE2 binding interaction. Int Immunopharmacol. 2022 Nov;112:109280. doi: 10.1016/j.intimp.2022.109280. Epub 2022 Sep 28. PMID: 36183680; PMCID: PMC9515349.
Schlottau K, Rissmann M, Graaf A, Schön J, Sehl J, Wylezich C, Höper D, Mettenleiter TC, Balkema-Buschmann A, Harder T, Grund C, Hoffmann D, Breithaupt A, Beer M. SARS-CoV-2 in fruit bats, ferrets, pigs, and chickens: an experimental transmission study. Lancet Microbe. 2020 Sep;1(5):e218-e225. doi: 10.1016/S2666-5247(20)30089-6. Epub 2020 Jul 7. PMID: 32838346; PMCID: PMC7340389.

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