TY - JOUR T1 - Low-Dose Ad26.COV2.S Protection Against SARS-CoV-2 Challenge in Rhesus Macaques JF - bioRxiv DO - 10.1101/2021.01.27.428380 SP - 2021.01.27.428380 AU - Xuan He AU - Abishek Chandrashekar AU - Roland Zahn AU - Frank Wegmann AU - Jingyou Yu AU - Noe B. Mercado AU - Katherine McMahan AU - Amanda J. Martinot AU - Cesar Piedra-Mora AU - Sidney Beecy AU - Sarah Ducat AU - Ronnie Chamanza AU - Sietske Rosendahl Huber AU - Leslie van der Fits AU - Erica N. Borducchi AU - Michelle Lifton AU - Jinyan Liu AU - Felix Nampanya AU - Shivani Patel AU - Lauren Peter AU - Lisa H. Tostanoski AU - Laurent Pessaint AU - Alex Van Ry AU - Brad Finneyfrock AU - Jason Velasco AU - Elyse Teow AU - Renita Brown AU - Anthony Cook AU - Hanne Andersen AU - Mark G. Lewis AU - Hanneke Schuitemaker AU - Dan H. Barouch Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/01/27/2021.01.27.428380.abstract N2 - We previously reported that a single immunization with an adenovirus serotype 26 (Ad26) vector-based vaccine expressing an optimized SARS-CoV-2 spike (Ad26.COV2.S) protected rhesus macaques against SARS-CoV-2 challenge. In this study, we evaluated the immunogenicity and protective efficacy of reduced doses of Ad26.COV2.S. 30 rhesus macaques were immunized once with 1×1011, 5×1010, 1.125×1010, or 2×109 vp Ad26.COV2.S or sham and were challenged with SARS-CoV-2 by the intranasal and intratracheal routes. Vaccine doses as low as 2×109 vp provided robust protection in bronchoalveolar lavage, whereas doses of 1.125×1010 vp were required for protection in nasal swabs. Activated memory B cells as well as binding and neutralizing antibody titers following vaccination correlated with protective efficacy. At suboptimal vaccine doses, viral breakthrough was observed but did not show evidence of virologic, immunologic, histopathologic, or clinical enhancement of disease compared with sham controls. These data demonstrate that a single immunization with a relatively low dose of Ad26.COV2.S effectively protected against SARS-CoV-2 challenge in rhesus macaques. Moreover, our findings show that a higher vaccine dose may be required for protection in the upper respiratory tract compared with the lower respiratory tract.Competing Interest StatementD.H.B., R.Z., F.W. and H.S. are co-inventors on related vaccine patents. R.Z., F.W., R.C., S.R.H., L.vd.F. and H.S. are employees of Janssen and may hold stock in Johnson & Johnson. ER -