Low-dose Ad26.COV2.S protection against SARS-CoV-2 challenge in rhesus macaques.
Xuan He, Abishek Chandrashekar, Roland Zahn, Frank Wegmann, Jingyou Yu, Noe B Mercado, Katherine McMahan, Amanda J Martinot, Cesar Piedra-Mora, Sidney Beecy, Sarah Ducat, Ronnie Chamanza, Sietske Rosendahl Huber, Marjolein van Heerden, Leslie van der Fits, Erica N Borducchi, Michelle Lifton, Jinyan Liu, Felix Nampanya, Shivani Patel, Lauren Peter, Lisa H Tostanoski, Laurent Pessaint, Alex Van Ry, Brad Finneyfrock, Jason Velasco, Elyse Teow, Renita Brown, Anthony Cook, Hanne Andersen, Mark G Lewis, Hanneke Schuitemaker, Dan H Barouch
Author Information
Xuan He: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Abishek Chandrashekar: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Roland Zahn: Janssen Vaccines & Prevention BV, Leiden, the Netherlands.
Frank Wegmann: Janssen Vaccines & Prevention BV, Leiden, the Netherlands.
Jingyou Yu: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Noe B Mercado: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Katherine McMahan: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Amanda J Martinot: Tufts University Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA.
Cesar Piedra-Mora: Tufts University Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA.
Sidney Beecy: Tufts University Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA.
Sarah Ducat: Tufts University Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA.
Ronnie Chamanza: Janssen Vaccines & Prevention BV, Leiden, the Netherlands.
Marjolein van Heerden: Janssen Vaccines & Prevention BV, Leiden, the Netherlands.
Leslie van der Fits: Janssen Vaccines & Prevention BV, Leiden, the Netherlands.
Erica N Borducchi: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Michelle Lifton: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Jinyan Liu: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Felix Nampanya: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Shivani Patel: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Lauren Peter: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Lisa H Tostanoski: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Laurent Pessaint: Bioqual, Rockville, MD 20852, USA.
Alex Van Ry: Bioqual, Rockville, MD 20852, USA.
Brad Finneyfrock: Bioqual, Rockville, MD 20852, USA.
Jason Velasco: Bioqual, Rockville, MD 20852, USA.
Elyse Teow: Bioqual, Rockville, MD 20852, USA.
Renita Brown: Bioqual, Rockville, MD 20852, USA.
Anthony Cook: Bioqual, Rockville, MD 20852, USA.
Hanne Andersen: Bioqual, Rockville, MD 20852, USA.
Mark G Lewis: Bioqual, Rockville, MD 20852, USA.
Hanneke Schuitemaker: Janssen Vaccines & Prevention BV, Leiden, the Netherlands.
Dan H Barouch: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Massachusetts Consortium on Pathogen Readiness, Boston, MA 02215, USA. Electronic address: dbarouch@bidmc.harvard.edu.
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. To evaluate reduced doses of Ad26.COV2.S, 30 rhesus macaques were immunized once with 1 × 10, 5 × 10, 1.125 × 10, or 2 × 10 viral particles (vp) Ad26.COV2.S or sham and were challenged with SARS-CoV-2. Vaccine doses as low as 2 × 10 vp provided robust protection in bronchoalveolar lavage, whereas doses of 1.125 × 10 vp were required for protection in nasal swabs. Activated memory B cells and binding or neutralizing antibody titers following vaccination correlated with protective efficacy. At suboptimal vaccine doses, viral breakthrough was observed but did not show enhancement of disease. These data demonstrate that a single immunization with relatively low dose of Ad26.COV2.S effectively protected against SARS-CoV-2 challenge in rhesus macaques, although a higher vaccine dose may be required for protection in the upper respiratory tract.
