TY - JOUR
T1 - Egg-Derived Anti-SARS-CoV-2 Immunoglobulin Y (IgY) With Broad Variant Activity as Intranasal Prophylaxis Against COVID-19
AU - Frumkin, Lyn R.
AU - Lucas, Michaela
AU - Scribner, Curtis L.
AU - Ortega-Heinly, Nastassja
AU - Rogers, Jayden
AU - Yin, Gang
AU - Hallam, Trevor J.
AU - Yam, Alice
AU - Bedard, Kristin
AU - Begley, Rebecca
AU - Cohen, Courtney A.
AU - Badger, Catherine V.
AU - Abbasi, Shawn A.
AU - Dye, John M.
AU - McMillan, Brian
AU - Wallach, Michael
AU - Bricker, Traci L.
AU - Joshi, Astha
AU - Boon, Adrianus C.M.
AU - Pokhrel, Suman
AU - Kraemer, Benjamin R.
AU - Lee, Lucia
AU - Kargotich, Stephen
AU - Agochiya, Mahima
AU - John, Tom St
AU - Mochly-Rosen, Daria
N1 - Publisher Copyright:
Copyright © 2022 Frumkin, Lucas, Scribner, Ortega-Heinly, Rogers, Yin, Hallam, Yam, Bedard, Begley, Cohen, Badger, Abbasi, Dye, McMillan, Wallach, Bricker, Joshi, Boon, Pokhrel, Kraemer, Lee, Kargotich, Agochiya, John and Mochly-Rosen.
PY - 2022/6/1
Y1 - 2022/6/1
N2 - COVID-19 emergency use authorizations and approvals for vaccines were achieved in record time. However, there remains a need to develop additional safe, effective, easy-to-produce, and inexpensive prevention to reduce the risk of acquiring SARS-CoV-2 infection. This need is due to difficulties in vaccine manufacturing and distribution, vaccine hesitancy, and, critically, the increased prevalence of SARS-CoV-2 variants with greater contagiousness or reduced sensitivity to immunity. Antibodies from eggs of hens (immunoglobulin Y; IgY) that were administered the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein were developed for use as nasal drops to capture the virus on the nasal mucosa. Although initially raised against the 2019 novel coronavirus index strain (2019-nCoV), these anti-SARS-CoV-2 RBD IgY surprisingly had indistinguishable enzyme-linked immunosorbent assay binding against variants of concern that have emerged, including Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529). This is different from sera of immunized or convalescent patients. Culture neutralization titers against available Alpha, Beta, and Delta were also indistinguishable from the index SARS-CoV-2 strain. Efforts to develop these IgY for clinical use demonstrated that the intranasal anti-SARS-CoV-2 RBD IgY preparation showed no binding (cross-reactivity) to a variety of human tissues and had an excellent safety profile in rats following 28-day intranasal delivery of the formulated IgY. A double-blind, randomized, placebo-controlled phase 1 study evaluating single-ascending and multiple doses of anti-SARS-CoV-2 RBD IgY administered intranasally for 14 days in 48 healthy adults also demonstrated an excellent safety and tolerability profile, and no evidence of systemic absorption. As these antiviral IgY have broad selectivity against many variants of concern, are fast to produce, and are a low-cost product, their use as prophylaxis to reduce SARS-CoV-2 viral transmission warrants further evaluation. Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/show/NCT04567810, identifier NCT04567810.
AB - COVID-19 emergency use authorizations and approvals for vaccines were achieved in record time. However, there remains a need to develop additional safe, effective, easy-to-produce, and inexpensive prevention to reduce the risk of acquiring SARS-CoV-2 infection. This need is due to difficulties in vaccine manufacturing and distribution, vaccine hesitancy, and, critically, the increased prevalence of SARS-CoV-2 variants with greater contagiousness or reduced sensitivity to immunity. Antibodies from eggs of hens (immunoglobulin Y; IgY) that were administered the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein were developed for use as nasal drops to capture the virus on the nasal mucosa. Although initially raised against the 2019 novel coronavirus index strain (2019-nCoV), these anti-SARS-CoV-2 RBD IgY surprisingly had indistinguishable enzyme-linked immunosorbent assay binding against variants of concern that have emerged, including Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529). This is different from sera of immunized or convalescent patients. Culture neutralization titers against available Alpha, Beta, and Delta were also indistinguishable from the index SARS-CoV-2 strain. Efforts to develop these IgY for clinical use demonstrated that the intranasal anti-SARS-CoV-2 RBD IgY preparation showed no binding (cross-reactivity) to a variety of human tissues and had an excellent safety profile in rats following 28-day intranasal delivery of the formulated IgY. A double-blind, randomized, placebo-controlled phase 1 study evaluating single-ascending and multiple doses of anti-SARS-CoV-2 RBD IgY administered intranasally for 14 days in 48 healthy adults also demonstrated an excellent safety and tolerability profile, and no evidence of systemic absorption. As these antiviral IgY have broad selectivity against many variants of concern, are fast to produce, and are a low-cost product, their use as prophylaxis to reduce SARS-CoV-2 viral transmission warrants further evaluation. Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/show/NCT04567810, identifier NCT04567810.
KW - COVID-19
KW - IgY
KW - SARS-CoV-2
KW - chicken immunoglobulin
KW - clinical trial body
KW - immunoglobulin Y
KW - infectious diseases
UR - http://www.scopus.com/inward/record.url?scp=85132289508&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2022.899617
DO - 10.3389/fimmu.2022.899617
M3 - Article
C2 - 35720389
AN - SCOPUS:85132289508
SN - 1664-3224
VL - 13
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 899617
ER -