Protective Efficacy of Gastrointestinal SARS-CoV-2 Delivery against Intranasal and Intratracheal SARS-CoV-2 Challenge in Rhesus Macaques.
Jingyou Yu, Natalie D Collins, Noe B Mercado, Katherine McMahan, Abishek Chandrashekar, Jinyan Liu, Tochi Anioke, Aiquan Chang, Victoria M Giffin, David L Hope, Daniel Sellers, Felix Nampanya, Sarah Gardner, Julia Barrett, Huahua Wan, Jason Velasco, Elyse Teow, Anthony Cook, Alex Van Ry, Laurent Pessaint, Hanne Andersen, Mark G Lewis, Christian Hofer, Donald S Burke, Erica K Barkei, Hannah A D King, Caroline Subra, Diane Bolton, Kayvon Modjarrad, Nelson L Michael, Dan H Barouch
Author Information
Jingyou Yu: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.
Natalie D Collins: Walter Reed National Military Medical Center, Bethesda, Maryland, USA.
Noe B Mercado: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA. ORCID
Katherine McMahan: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.
Abishek Chandrashekar: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.
Jinyan Liu: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.
Tochi Anioke: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.
Aiquan Chang: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.
Victoria M Giffin: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.
David L Hope: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.
Daniel Sellers: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.
Felix Nampanya: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.
Sarah Gardner: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.
Julia Barrett: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.
Huahua Wan: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.
Jason Velasco: Bioqual, Rockville, Maryland, USA.
Elyse Teow: Bioqual, Rockville, Maryland, USA.
Anthony Cook: Bioqual, Rockville, Maryland, USA.
Alex Van Ry: Bioqual, Rockville, Maryland, USA.
Laurent Pessaint: Bioqual, Rockville, Maryland, USA.
Hanne Andersen: Bioqual, Rockville, Maryland, USA.
Mark G Lewis: Bioqual, Rockville, Maryland, USA.
Christian Hofer: Veterinary Services Program, Center for Enabling Capabilities, Walter Reed Army Institute for Research, Silver Spring, Maryland, USA.
Donald S Burke: Graduate School of Public Health, University of Pittsburghgrid.21925.3d, Pittsburgh, Pennsylvania, USA.
Erica K Barkei: Veterinary Services Program, Center for Enabling Capabilities, Walter Reed Army Institute for Research, Silver Spring, Maryland, USA.
Hannah A D King: Henry Jackson Foundation, Bethesda, Maryland, USA.
Caroline Subra: Henry Jackson Foundation, Bethesda, Maryland, USA.
Diane Bolton: Henry Jackson Foundation, Bethesda, Maryland, USA.
Kayvon Modjarrad: Emerging Infectious Diseases Branch, Center for Infectious Disease Research, Walter Reed Army Institute for Research, Silver Spring, Maryland, USA.
Nelson L Michael: Center for Infectious Disease Research, Walter Reed Army Institute for Research, Silver Spring, Maryland, USA.
Dan H Barouch: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA. ORCID
Live oral vaccines have been explored for their protective efficacy against respiratory viruses, particularly for adenovirus serotypes 4 and 7. The potential of a live oral vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), however, remains unclear. In this study, we assessed the immunogenicity of live SARS-CoV-2 delivered to the gastrointestinal tract in rhesus macaques and its protective efficacy against intranasal and intratracheal SARS-CoV-2 challenge. Postpyloric administration of SARS-CoV-2 by esophagogastroduodenoscopy resulted in limited virus replication in the gastrointestinal tract and minimal to no induction of mucosal antibody titers in rectal swabs, nasal swabs, and bronchoalveolar lavage fluid. Low levels of serum neutralizing antibodies were induced and correlated with modestly diminished viral loads in nasal swabs and bronchoalveolar lavage fluid following intranasal and intratracheal SARS-CoV-2 challenge. Overall, our data show that postpyloric inoculation of live SARS-CoV-2 is weakly immunogenic and confers partial protection against respiratory SARS-CoV-2 challenge in rhesus macaques. SARS-CoV-2 remains a global threat, despite the rapid deployment but limited coverage of multiple vaccines. Alternative vaccine strategies that have favorable manufacturing timelines, greater ease of distribution, and improved coverage may offer significant public health benefits, especially in resource-limited settings. Live oral vaccines have the potential to address some of these limitations; however, no studies have yet been conducted to assess the immunogenicity and protective efficacy of a live oral vaccine against SARS-CoV-2. Here, we report that oral administration of live SARS-CoV-2 in nonhuman primates may offer prophylactic benefits, but the formulation and route of administration will require further optimization.
