Replication-Competent Vesicular Stomatitis Virus Vaccine Vector Protects against SARS-CoV-2-Mediated Pathogenesis in Mice

James Brett Case; Paul W. Rothlauf; Rita E. Chen; Natasha M. Kafai; Julie M. Fox; Brittany K. Smith; Swathi Shrihari; Broc T. McCune; Ian B. Harvey; Shamus P. Keeler; Louis Marie Bloyet; Haiyan Zhao; Meisheng Ma; Lucas J. Adams; Emma S. Winkler; Michael J. Holtzman; Daved H. Fremont; Sean P.J. Whelan; Michael S. Diamond

doi:10.1016/j.chom.2020.07.018

Replication-Competent Vesicular Stomatitis Virus Vaccine Vector Protects against SARS-CoV-2-Mediated Pathogenesis in Mice

James Brett Case, Paul W. Rothlauf, Rita E. Chen, Natasha M. Kafai, Julie M. Fox, Brittany K. Smith, Swathi Shrihari, Broc T. McCune, Ian B. Harvey, Shamus P. Keeler, Louis Marie Bloyet, Haiyan Zhao, Meisheng Ma, Lucas J. Adams, Emma S. Winkler, Michael J. Holtzman, Daved H. Fremont, Sean P.J. Whelan, Michael S. Diamond

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138 Scopus citations

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of human infections, and an effective vaccine is critical to mitigate coronavirus-induced disease 2019 (COVID-19). Previously, we developed a replication-competent vesicular stomatitis virus (VSV) expressing a modified form of the SARS-CoV-2 spike gene in place of the native glycoprotein gene (VSV-eGFP-SARS-CoV-2). Here, we show that vaccination with VSV-eGFP-SARS-CoV-2 generates neutralizing immune responses and protects mice from SARS-CoV-2. Immunization of mice with VSV-eGFP-SARS-CoV-2 elicits high antibody titers that neutralize SARS-CoV-2 and target the receptor binding domain that engages human angiotensin-converting enzyme-2 (ACE2). Upon challenge with a human isolate of SARS-CoV-2, mice that expressed human ACE2 and were immunized with VSV-eGFP-SARS-CoV-2 show profoundly reduced viral infection and inflammation in the lung, indicating protection against pneumonia. Passive transfer of sera from VSV-eGFP-SARS-CoV-2-immunized animals also protects naive mice from SARS-CoV-2 challenge. These data support development of VSV-SARS-CoV-2 as an attenuated, replication-competent vaccine against SARS-CoV-2.

Original language	English
Pages (from-to)	465-474.e4
Journal	Cell Host and Microbe
Volume	28
Issue number	3
DOIs	https://doi.org/10.1016/j.chom.2020.07.018
State	Published - Sep 9 2020

Keywords

COVID-19
SARS-CoV-2
correlates
humoral immunity
immunity
neutralizing antibodies
vaccine
vesicular stomatitis virus

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10.1016/j.chom.2020.07.018

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Case, J. B., Rothlauf, P. W., Chen, R. E., Kafai, N. M., Fox, J. M., Smith, B. K., Shrihari, S., McCune, B. T., Harvey, I. B., Keeler, S. P., Bloyet, L. M., Zhao, H., Ma, M., Adams, L. J., Winkler, E. S., Holtzman, M. J., Fremont, D. H., Whelan, S. P. J., & Diamond, M. S. (2020). Replication-Competent Vesicular Stomatitis Virus Vaccine Vector Protects against SARS-CoV-2-Mediated Pathogenesis in Mice. Cell Host and Microbe, 28(3), 465-474.e4. https://doi.org/10.1016/j.chom.2020.07.018

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title = "Replication-Competent Vesicular Stomatitis Virus Vaccine Vector Protects against SARS-CoV-2-Mediated Pathogenesis in Mice",

abstract = "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of human infections, and an effective vaccine is critical to mitigate coronavirus-induced disease 2019 (COVID-19). Previously, we developed a replication-competent vesicular stomatitis virus (VSV) expressing a modified form of the SARS-CoV-2 spike gene in place of the native glycoprotein gene (VSV-eGFP-SARS-CoV-2). Here, we show that vaccination with VSV-eGFP-SARS-CoV-2 generates neutralizing immune responses and protects mice from SARS-CoV-2. Immunization of mice with VSV-eGFP-SARS-CoV-2 elicits high antibody titers that neutralize SARS-CoV-2 and target the receptor binding domain that engages human angiotensin-converting enzyme-2 (ACE2). Upon challenge with a human isolate of SARS-CoV-2, mice that expressed human ACE2 and were immunized with VSV-eGFP-SARS-CoV-2 show profoundly reduced viral infection and inflammation in the lung, indicating protection against pneumonia. Passive transfer of sera from VSV-eGFP-SARS-CoV-2-immunized animals also protects naive mice from SARS-CoV-2 challenge. These data support development of VSV-SARS-CoV-2 as an attenuated, replication-competent vaccine against SARS-CoV-2.",

keywords = "COVID-19, SARS-CoV-2, correlates, humoral immunity, immunity, neutralizing antibodies, vaccine, vesicular stomatitis virus",

author = "Case, {James Brett} and Rothlauf, {Paul W.} and Chen, {Rita E.} and Kafai, {Natasha M.} and Fox, {Julie M.} and Smith, {Brittany K.} and Swathi Shrihari and McCune, {Broc T.} and Harvey, {Ian B.} and Keeler, {Shamus P.} and Bloyet, {Louis Marie} and Haiyan Zhao and Meisheng Ma and Adams, {Lucas J.} and Winkler, {Emma S.} and Holtzman, {Michael J.} and Fremont, {Daved H.} and Whelan, {Sean P.J.} and Diamond, {Michael S.}",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2020",

month = sep,

day = "9",

doi = "10.1016/j.chom.2020.07.018",

language = "English",

volume = "28",

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journal = "Cell Host and Microbe",

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Case, JB, Rothlauf, PW, Chen, RE, Kafai, NM, Fox, JM, Smith, BK, Shrihari, S, McCune, BT, Harvey, IB, Keeler, SP, Bloyet, LM, Zhao, H, Ma, M, Adams, LJ, Winkler, ES, Holtzman, MJ , Fremont, DH , Whelan, SPJ & Diamond, MS 2020, 'Replication-Competent Vesicular Stomatitis Virus Vaccine Vector Protects against SARS-CoV-2-Mediated Pathogenesis in Mice', Cell Host and Microbe, vol. 28, no. 3, pp. 465-474.e4. https://doi.org/10.1016/j.chom.2020.07.018

TY - JOUR

T1 - Replication-Competent Vesicular Stomatitis Virus Vaccine Vector Protects against SARS-CoV-2-Mediated Pathogenesis in Mice

AU - Case, James Brett

AU - Rothlauf, Paul W.

AU - Chen, Rita E.

AU - Kafai, Natasha M.

AU - Fox, Julie M.

AU - Smith, Brittany K.

AU - Shrihari, Swathi

AU - McCune, Broc T.

AU - Harvey, Ian B.

AU - Keeler, Shamus P.

AU - Bloyet, Louis Marie

AU - Zhao, Haiyan

AU - Ma, Meisheng

AU - Adams, Lucas J.

AU - Winkler, Emma S.

AU - Holtzman, Michael J.

AU - Fremont, Daved H.

AU - Whelan, Sean P.J.

AU - Diamond, Michael S.

PY - 2020/9/9

Y1 - 2020/9/9

N2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of human infections, and an effective vaccine is critical to mitigate coronavirus-induced disease 2019 (COVID-19). Previously, we developed a replication-competent vesicular stomatitis virus (VSV) expressing a modified form of the SARS-CoV-2 spike gene in place of the native glycoprotein gene (VSV-eGFP-SARS-CoV-2). Here, we show that vaccination with VSV-eGFP-SARS-CoV-2 generates neutralizing immune responses and protects mice from SARS-CoV-2. Immunization of mice with VSV-eGFP-SARS-CoV-2 elicits high antibody titers that neutralize SARS-CoV-2 and target the receptor binding domain that engages human angiotensin-converting enzyme-2 (ACE2). Upon challenge with a human isolate of SARS-CoV-2, mice that expressed human ACE2 and were immunized with VSV-eGFP-SARS-CoV-2 show profoundly reduced viral infection and inflammation in the lung, indicating protection against pneumonia. Passive transfer of sera from VSV-eGFP-SARS-CoV-2-immunized animals also protects naive mice from SARS-CoV-2 challenge. These data support development of VSV-SARS-CoV-2 as an attenuated, replication-competent vaccine against SARS-CoV-2.

AB - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of human infections, and an effective vaccine is critical to mitigate coronavirus-induced disease 2019 (COVID-19). Previously, we developed a replication-competent vesicular stomatitis virus (VSV) expressing a modified form of the SARS-CoV-2 spike gene in place of the native glycoprotein gene (VSV-eGFP-SARS-CoV-2). Here, we show that vaccination with VSV-eGFP-SARS-CoV-2 generates neutralizing immune responses and protects mice from SARS-CoV-2. Immunization of mice with VSV-eGFP-SARS-CoV-2 elicits high antibody titers that neutralize SARS-CoV-2 and target the receptor binding domain that engages human angiotensin-converting enzyme-2 (ACE2). Upon challenge with a human isolate of SARS-CoV-2, mice that expressed human ACE2 and were immunized with VSV-eGFP-SARS-CoV-2 show profoundly reduced viral infection and inflammation in the lung, indicating protection against pneumonia. Passive transfer of sera from VSV-eGFP-SARS-CoV-2-immunized animals also protects naive mice from SARS-CoV-2 challenge. These data support development of VSV-SARS-CoV-2 as an attenuated, replication-competent vaccine against SARS-CoV-2.

KW - COVID-19

KW - SARS-CoV-2

KW - correlates

KW - humoral immunity

KW - immunity

KW - neutralizing antibodies

KW - vaccine

KW - vesicular stomatitis virus

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U2 - 10.1016/j.chom.2020.07.018

DO - 10.1016/j.chom.2020.07.018

M3 - Article

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AN - SCOPUS:85089456440

SN - 1931-3128

VL - 28

SP - 465-474.e4

JO - Cell Host and Microbe

JF - Cell Host and Microbe

IS - 3

ER -

Replication-Competent Vesicular Stomatitis Virus Vaccine Vector Protects against SARS-CoV-2-Mediated Pathogenesis in Mice

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