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

doi:10.1128/JVI.01599-21

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 PessaintHanne 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

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.

Original language	English
Article number	e01599-21
Journal	Journal of Virology
Volume	96
Issue number	2
DOIs	https://doi.org/10.1128/JVI.01599-21
State	Published - Jan 2022
Externally published	Yes

Keywords

COVID-19
Immunogenicity
Live oral vaccine
Protective efficacy
SARS-CoV-2

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10.1128/JVI.01599-21

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Yu, J., Collins, N. D., Mercado, N. B., McMahan, K., Chandrashekar, A., Liu, J., Anioke, T., Chang, A., Giffin, V. M., Hope, D. L., Sellers, D., Nampanya, F., Gardner, S., Barrett, J., Wan, H., Velasco, J., Teow, E., Cook, A., van Ry, A., ... Barouch, D. H. (2022). Protective Efficacy of Gastrointestinal SARS-CoV-2 Delivery against Intranasal and Intratracheal SARS-CoV-2 Challenge in Rhesus Macaques. Journal of Virology, 96(2), Article e01599-21. https://doi.org/10.1128/JVI.01599-21

@article{822f66c915434d21ad3f4f08805a693d,

title = "Protective Efficacy of Gastrointestinal SARS-CoV-2 Delivery against Intranasal and Intratracheal SARS-CoV-2 Challenge in Rhesus Macaques",

abstract = "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.",

keywords = "COVID-19, Immunogenicity, Live oral vaccine, Protective efficacy, SARS-CoV-2",

author = "Jingyou Yu and Collins, {Natalie D.} and Mercado, {Noe B.} and Katherine McMahan and Abishek Chandrashekar and Jinyan Liu and Tochi Anioke and Aiquan Chang and Giffin, {Victoria M.} and Hope, {David L.} and Daniel Sellers and Felix Nampanya and Sarah Gardner and Julia Barrett and Huahua Wan and Jason Velasco and Elyse Teow and Anthony Cook and {van Ry}, Alex and Laurent Pessaint and Hanne Andersen and Lewis, {Mark G.} and Christian Hofer and Burke, {Donald S.} and Barkei, {Erica K.} and King, {Hannah A.D.} and Caroline Subra and Diane Bolton and Kayvon Modjarrad and Michael, {Nelson L.} and Barouch, {Dan H.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2022 Yu et al.",

year = "2022",

month = jan,

doi = "10.1128/JVI.01599-21",

language = "English",

volume = "96",

journal = "Journal of Virology",

issn = "0022-538X",

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Yu, J, Collins, ND, Mercado, NB, McMahan, K, Chandrashekar, A, Liu, J, Anioke, T, Chang, A, Giffin, VM, Hope, DL, Sellers, D, Nampanya, F, Gardner, S, Barrett, J, Wan, H, Velasco, J, Teow, E, Cook, A, van Ry, A, Pessaint, L, Andersen, H, Lewis, MG, Hofer, C, Burke, DS, Barkei, EK, King, HAD, Subra, C, Bolton, D, Modjarrad, K, Michael, NL & Barouch, DH 2022, 'Protective Efficacy of Gastrointestinal SARS-CoV-2 Delivery against Intranasal and Intratracheal SARS-CoV-2 Challenge in Rhesus Macaques', Journal of Virology, vol. 96, no. 2, e01599-21. https://doi.org/10.1128/JVI.01599-21

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T1 - Protective Efficacy of Gastrointestinal SARS-CoV-2 Delivery against Intranasal and Intratracheal SARS-CoV-2 Challenge in Rhesus Macaques

AU - Yu, Jingyou

AU - Collins, Natalie D.

AU - Mercado, Noe B.

AU - McMahan, Katherine

AU - Chandrashekar, Abishek

AU - Liu, Jinyan

AU - Anioke, Tochi

AU - Chang, Aiquan

AU - Giffin, Victoria M.

AU - Hope, David L.

AU - Sellers, Daniel

AU - Nampanya, Felix

AU - Gardner, Sarah

AU - Barrett, Julia

AU - Wan, Huahua

AU - Velasco, Jason

AU - Teow, Elyse

AU - Cook, Anthony

AU - van Ry, Alex

AU - Pessaint, Laurent

AU - Andersen, Hanne

AU - Lewis, Mark G.

AU - Hofer, Christian

AU - Burke, Donald S.

AU - Barkei, Erica K.

AU - King, Hannah A.D.

AU - Subra, Caroline

AU - Bolton, Diane

AU - Modjarrad, Kayvon

AU - Michael, Nelson L.

AU - Barouch, Dan H.

PY - 2022/1

Y1 - 2022/1

N2 - 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.

AB - 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.

KW - COVID-19

KW - Immunogenicity

KW - Live oral vaccine

KW - Protective efficacy

KW - SARS-CoV-2

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U2 - 10.1128/JVI.01599-21

DO - 10.1128/JVI.01599-21

M3 - Article

C2 - 34705557

AN - SCOPUS:85123830823

SN - 0022-538X

VL - 96

JO - Journal of Virology

JF - Journal of Virology

IS - 2

M1 - e01599-21

ER -

Protective Efficacy of Gastrointestinal SARS-CoV-2 Delivery against Intranasal and Intratracheal SARS-CoV-2 Challenge in Rhesus Macaques

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Keywords

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