2021年7月1日木曜日

アカゲザルに対するAd26.COV2.Sワクチンの免疫反応評価

 Jingyou Yu, Lisa H. Tostanoski, Noe B. Mercado, Katherine McMahan, Jinyan Liu, Catherine Jacob-Dolan, Abishek Chandrashekar et al investigate both humoral and cellular immunity of Ad26.COV2.S vaccine for SARS-CoV-2 B.1.351 lineage in rhesus macaques(1).
//Vaccine information//---
 Ad26.COV2.S vaccine: Janssen Vaccines & Prevention, Leiden, The Netherlands
(Vaccine type)
 Viral vector vaccine based on a human adenovirus that has been modified to contain the gene for making the spike protein of the SARS-CoV-2
 This vaccine may be stored between 9 to 25 degC(48 to 77F) for up to twelve hour(2).
//B.1.351 lineage: Beta linage//---
 After November/2020, this lineage spread mainly from South Africa. This linage has at least three key mutations, N501Y, N417N, E484K. To my knowledge, the epidemic lineage has N501Y which makes binding affinity for ACEs receptor high. Additionally, E484K has escape trait for emergent antibody. Therefore, neutralization ability of antibody significantly decreases.
// The clinical trial result of Ad26.COV2.S vaccine for B.1.351 lineage(3)//---
 95% of the object person in this clinical trial(NCT04505722) has B.1.351 lineage.
 Vaccine efficacy for infection: 66.1%
 Vaccine efficacy for severe symptom: 85.4%
 Therefore, moderate efficacy for infection and high efficacy for severe symptom have been confirmed.
//Humoral immunity in rhesus macaques(1)//---
 The Nab titer of B.1.351 for WA1/2020 decreases by 4.5 fold at week 6 after vaccination.
 (See Fig.1B)
//Cellular immunity in rhesus macaques(1)//---
 CD4 T cell and CD8 T cell is comparable between B.1.351 and WA1/2020.
 (See Fig.2B)
//Virus road in rhesus macaques(1)//---
The peak virus road (Log sgRNA copies/ml) significantly reduces by 2.33log via Ad26.COV2.S vaccination for non-vaccination in both BAL and Nasal swab. At 4 days after virus injection, virus road is below detection lower limit. However, in non-vaccination case, virus load over detection limit maintains over 10 days. Therefore, the rationale for the prevention of severe symptom in human is indicated. (See Fig.3)
 
(Reference)
(1)
Jingyou Yu, Lisa H. Tostanoski, Noe B. Mercado, Katherine McMahan, Jinyan Liu, Catherine Jacob-Dolan, Abishek Chandrashekar, Caroline Atyeo, David R. Martinez, Tochi Anioke, Esther A. Bondzie, Aiquan Chang, Sarah Gardner, Victoria M. Giffin, David L. Hope, Felix Nampanya, Joseph Nkolola, Shivani Patel, Owen Sanborn, Daniel Sellers, Huahua Wan, Tammy Hayes, Katherine Bauer, Laurent Pessaint, Daniel Valentin, Zack Flinchbaugh, Renita Brown, Anthony Cook, Deandre Bueno-Wilkerson, Elyse Teow, Hanne Andersen, Mark G. Lewis, Amanda J. Martinot, Ralph S. Baric, Galit Alter, Frank Wegmann, Roland Zahn, Hanneke Schuitemaker & Dan H. Barouch
Protective efficacy of Ad26.COV2.S against SARS-CoV-2 B.1.351 in macaques
Nature (2021)
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Author information
Author notes
These authors contributed equally: Jingyou Yu, Lisa H. Tostanoski, Noe B. Mercado, Katherine McMahan, Jinyan Liu, Catherine Jacob-Dolan, Abishek Chandrashekar
Affiliations
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Jingyou Yu, Lisa H. Tostanoski, Noe B. Mercado, Katherine McMahan, Jinyan Liu, Catherine Jacob-Dolan, Abishek Chandrashekar, Tochi Anioke, Esther A. Bondzie, Aiquan Chang, Sarah Gardner, Victoria M. Giffin, David L. Hope, Felix Nampanya, Joseph Nkolola, Shivani Patel, Owen Sanborn, Daniel Sellers, Huahua Wan & Dan H. Barouch
Harvard Medical School, Boston, MA, USA
Catherine Jacob-Dolan, Caroline Atyeo, Aiquan Chang & Dan H. Barouch
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA
Caroline Atyeo, Galit Alter & Dan H. Barouch
University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
David R. Martinez & Ralph S. Baric
Tufts University Cummings School of Veterinary Medicine, North Grafton, MA, USA
Tammy Hayes, Katherine Bauer & Amanda J. Martinot
Bioqual, Rockville, MD, 20852, USA
Laurent Pessaint, Daniel Valentin, Zack Flinchbaugh, Renita Brown, Anthony Cook, Deandre Bueno-Wilkerson, Elyse Teow, Hanne Andersen & Mark G. Lewis
Janssen Vaccines & Prevention, Leiden, The Netherlands
Frank Wegmann, Roland Zahn & Hanneke Schuitemaker
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(2)
 "Fact Sheet for Healthcare Providers Administering Vaccine and EUA" (PDF). Janssen. Archived from the original on 13 April 2021. Retrieved 13 April 2021
(3)
Jerald Sadoff, M.D., Glenda Gray, M.B., B.Ch., An Vandebosch, Ph.D., Vicky Cárdenas, Ph.D., Georgi Shukarev, M.D., Beatriz Grinsztejn, M.D., Paul A. Goepfert, M.D., Carla Truyers, Ph.D., Hein Fennema, Ph.D., Bart Spiessens, Ph.D., Kim Offergeld, M.Sc., Gert Scheper, Ph.D., Kimberly L. Taylor, Ph.D., Merlin L. Robb, M.D., John Treanor, M.D., Dan H. Barouch, M.D., Jeffrey Stoddard, M.D., Martin F. Ryser, M.D., Mary A. Marovich, M.D., Kathleen M. Neuzil, M.D., Lawrence Corey, M.D., Nancy Cauwenberghs, Ph.D., Tamzin Tanner, Ph.D., Karin Hardt, Ph.D., Javier Ruiz-Guiñazú, M.D., Mathieu Le Gars, Ph.D., Hanneke Schuitemaker, Ph.D., Johan Van Hoof, M.D., Frank Struyf, M.D., and Macaya Douoguih, M.D. for the ENSEMBLE Study Group*
Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19
The New England Journal of Medicine 2021; 384:2187-2201
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Author Affiliations
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, G. Scheper, M.L.G., H.S., J.V.H., M.D.); South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., H.F., B.S., K.O., M.F.R., N.C., T.T., K.H., J.R.G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases–Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); the National Institute of Allergy and Infectious Diseases, Rockville (K.L.T., M.A.M.), Walter Reed Army Institute of Research, Silver Spring (M.L.R.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) — all in Maryland; Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); Janssen Research and Development, Raritan, NJ (J. Stoddard); and Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.).
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