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Egg-derived anti-SARS-CoV-2 immunoglobulin Y (IgY) with broad variant activity as intranasal prophylaxis against COVID-19: preclinical studies and randomized controlled phase 1 clinical trial
Lyn Frumkin; Michaela Lucas; Curt Scribner; Nastassja Ortega-Heinly; Jayden Rogers; Gang Yin; Trevor J Hallam; Alice Yam; Kristin Bedard; Rebecca Begley; Courtney A Cohen; Catherine V Badger; Shawn A Abbasi; John M Dye; Brian McMillan; Michael Wallach; Traci L Bricker; Astha Joshi; Adrianus C. M. Boon; Suman Pokhrel; Benjamin R Kraemer; Lucia Lee; Stephen Kargotich; Mahima Agogiya; Tom St. John; Daria Mochly-Rosen.
Afiliação
  • Lyn Frumkin; Stanford
  • Michaela Lucas; University of Western Australia
  • Curt Scribner; Independent Regulatory Consultant
  • Nastassja Ortega-Heinly; Charles River Laboratories
  • Jayden Rogers; Linear Clinical Research Ltd
  • Gang Yin; Sutro Biopharma Inc
  • Trevor J Hallam; Sutro Biopharma Inc
  • Alice Yam; Sutro Biopharma Inc
  • Kristin Bedard; Sutro Biopharma Inc
  • Rebecca Begley; Stanford University
  • Courtney A Cohen; United States Army Medical Research Institute of Medical Research of Infectious Diseases
  • Catherine V Badger; United States Army Medical Research Institute of Infectious Diseases
  • Shawn A Abbasi; United States Army Medical Research Institute of Infectious Diseases
  • John M Dye; United States Army Medical Research Institute of Infectious Diseases
  • Brian McMillan; Bravado Pharmaceuticals
  • Michael Wallach; University of Technology Sydney
  • Traci L Bricker; Washington University School of Medicine
  • Astha Joshi; Washington University School of Medicine
  • Adrianus C. M. Boon; Washington University School of Medicine
  • Suman Pokhrel; Stanford University School of Medicine
  • Benjamin R Kraemer; Stanford University
  • Lucia Lee; Stanford University
  • Stephen Kargotich; Stanford University
  • Mahima Agogiya; Stanford University
  • Tom St. John; Independent Scientist
  • Daria Mochly-Rosen; Stanford University
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22268914
ABSTRACT
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 receptor-binding domain (RBD) of the SARS-CoV-2 spike protein were developed 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 distinct for sera from 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. (ClinicalTrials.gov NCT04567810, https//www.clinicaltrials.gov/ct2/show/NCT04567810)
Licença
cc_by_nc_nd
Texto completo: Disponível Coleções: Preprints Base de dados: medRxiv Tipo de estudo: Experimental_studies / Estudo observacional / Estudo prognóstico / Rct Idioma: Inglês Ano de publicação: 2022 Tipo de documento: Preprint
Texto completo: Disponível Coleções: Preprints Base de dados: medRxiv Tipo de estudo: Experimental_studies / Estudo observacional / Estudo prognóstico / Rct Idioma: Inglês Ano de publicação: 2022 Tipo de documento: Preprint
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