Egg-Derived Anti-SARS-CoV-2 Immunoglobulin Y (IgY) With Broad Variant Activity as Intranasal Prophylaxis Against COVID-19.

Autor:	Frumkin LR; School of Medicine, SPARK at Stanford, Stanford University, Stanford, CA, United States., Lucas M; Faculty of Health and Medical Sciences Internal Medicine, The University of Western Australia, Perth, WA, Australia., Scribner CL; Independent Regulatory Consultant, Oakland, CA, United States., Ortega-Heinly N; Avian Vaccine Services, Charles River Laboratories, Storrs, CT, United States., Rogers J; Linear Clinical Research Ltd, Nedlands, WA, Australia., Yin G; Sutro Biopharma Inc., South San Francisco, CA, United States., Hallam TJ; Sutro Biopharma Inc., South San Francisco, CA, United States., Yam A; Sutro Biopharma Inc., South San Francisco, CA, United States., Bedard K; Sutro Biopharma Inc., South San Francisco, CA, United States., Begley R; School of Medicine, SPARK at Stanford, Stanford University, Stanford, CA, United States., Cohen CA; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United States.; The Geneva Foundation, Tacoma, WA, United States., Badger CV; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United States., Abbasi SA; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United States., Dye JM; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United States., McMillan B; Bravado Pharmaceuticals, Lutz, FL, United States., Wallach M; University of Technology Sydney, Sydney, NSW, Australia.; SPARK Sydney, Sydney, NSW, Australia., Bricker TL; Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States., Joshi A; Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States., Boon ACM; Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States., Pokhrel S; Department of Chemical and Systems Biology, Stanford University, School of Medicine, Stanford, CA, United States., Kraemer BR; Department of Chemical and Systems Biology, Stanford University, School of Medicine, Stanford, CA, United States., Lee L; Department of Chemical and Systems Biology, Stanford University, School of Medicine, Stanford, CA, United States., Kargotich S; School of Medicine, SPARK Global, Stanford University, Stanford, CA, United States., Agochiya M; School of Medicine, SPARK at Stanford, Stanford University, Stanford, CA, United States., John TS; School of Medicine, SPARK at Stanford, Stanford University, Stanford, CA, United States., Mochly-Rosen D; School of Medicine, SPARK at Stanford, Stanford University, Stanford, CA, United States.; Department of Chemical and Systems Biology, Stanford University, School of Medicine, Stanford, CA, United States.; School of Medicine, SPARK Global, Stanford University, Stanford, CA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Jun 01; Vol. 13, pp. 899617. Date of Electronic Publication: 2022 Jun 01 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.899617
Abstrakt:	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. Competing Interests: GY, TH, AY, and KB are affiliated with Sutro Biopharma, Inc; NO-H with Charles River Laboratories, Inc; JR, with Linear Clinical Research. Ltd; and BM with Bravado Pharmaceuticals, Inc. DM-R is named on a patent filed for composition and methods for passive immunization against viral infections such as SARS-CoV-2. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (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.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu