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Effective Prophylaxis of COVID-19 in Rhesus Macaques Using a Combination of Two Parenterally-Administered SARS-CoV-2 Neutralizing Antibodies.
Beddingfield, Brandon J; Maness, Nicholas J; Fears, Alyssa C; Rappaport, Jay; Aye, Pyone Pyone; Russell-Lodrigue, Kasi; Doyle-Meyers, Lara A; Blair, Robert V; Carias, Ann M; Madden, Patrick J; Redondo, Ramon Lorenzo; Gao, Hongmei; Montefiori, David; Hope, Thomas J; Roy, Chad J.
  • Beddingfield BJ; Divisions of Microbiology, Tulane National Primate Research Center, Covington, LA, United States.
  • Maness NJ; Divisions of Microbiology, Tulane National Primate Research Center, Covington, LA, United States.
  • Fears AC; Department of Microbiology and Immunology, Tulane School of Medicine, New Orleans, LA, United States.
  • Rappaport J; Divisions of Microbiology, Tulane National Primate Research Center, Covington, LA, United States.
  • Aye PP; Department of Microbiology and Immunology, Tulane School of Medicine, New Orleans, LA, United States.
  • Russell-Lodrigue K; Comparative Pathology, Tulane National Primate Research Center, Covington, LA, United States.
  • Doyle-Meyers LA; Comparative Pathology, Tulane National Primate Research Center, Covington, LA, United States.
  • Blair RV; Veterinary Medicine, Tulane National Primate Research Center, Covington, LA, United States.
  • Carias AM; Veterinary Medicine, Tulane National Primate Research Center, Covington, LA, United States.
  • Madden PJ; Comparative Pathology, Tulane National Primate Research Center, Covington, LA, United States.
  • Redondo RL; Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
  • Gao H; Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
  • Montefiori D; Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
  • Hope TJ; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, United States.
  • Roy CJ; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, United States.
Front Cell Infect Microbiol ; 11: 753444, 2021.
Article in English | MEDLINE | ID: covidwho-1555153
Preprint
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ABSTRACT
SARS-CoV-2 is a respiratory borne pathogenic beta coronavirus that is the source of a worldwide pandemic and the cause of multiple pathologies in man. The rhesus macaque model of COVID-19 was utilized to test the added benefit of combinatory parenteral administration of two high-affinity anti-SARS-CoV-2 monoclonal antibodies (mAbs; C144-LS and C135-LS) expressly developed to neutralize the virus and modified to extend their pharmacokinetics. After completion of kinetics study of mAbs in the primate, combination treatment was administered prophylactically to mucosal viral challenge. Results showed near complete virus neutralization evidenced by no measurable titer in mucosal tissue swabs, muting of cytokine/chemokine response, and lack of any discernable pathologic sequalae. Blocking infection was a dose-related effect, cohorts receiving lower doses (6, 2 mg/kg) resulted in low grade viral infection in various mucosal sites compared to that of a fully protective dose (20 mg/kg). A subset of animals within this cohort whose infectious challenge was delayed 75 days later after mAb administration were still protected from disease. Results indicate this combination mAb effectively blocks development of COVID-19 in the rhesus disease model and accelerates the prospect of clinical studies with this effective antibody combination.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Envelope Proteins / COVID-19 Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study Limits: Animals / Humans Language: English Journal: Front Cell Infect Microbiol Year: 2021 Document Type: Article Affiliation country: Fcimb.2021.753444

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Envelope Proteins / COVID-19 Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study Limits: Animals / Humans Language: English Journal: Front Cell Infect Microbiol Year: 2021 Document Type: Article Affiliation country: Fcimb.2021.753444