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

Cell Host Microbe. 2020 Sep 9;28(3):465-474.e4. doi: 10.1016/j.chom.2020.07.018. Epub 2020 Jul 30.

Authors

James Brett Case¹, Paul W Rothlauf², Rita E Chen³, Natasha M Kafai³, Julie M Fox¹, Brittany K Smith⁴, Swathi Shrihari¹, Broc T McCune¹, Ian B Harvey⁴, Shamus P Keeler⁵, Louis-Marie Bloyet⁶, Haiyan Zhao⁴, Meisheng Ma⁴, Lucas J Adams⁴, Emma S Winkler³, Michael J Holtzman⁵, Daved H Fremont⁷, Sean P J Whelan⁸, Michael S Diamond⁹

Affiliations

¹ Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
² Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA; Program in Virology, Harvard Medical School, Boston, MA, USA.
³ Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.
⁴ Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.
⁵ Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO, USA.
⁶ Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
⁷ Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA; Biochemistry & Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA.
⁸ Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: [email protected].
⁹ Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: [email protected].

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Angiotensin-Converting Enzyme 2
Animals
Antibodies, Neutralizing / blood
Antibodies, Viral / blood
Betacoronavirus* / immunology
Betacoronavirus* / pathogenicity
COVID-19
COVID-19 Vaccines
Chlorocebus aethiops
Coronavirus Infections / genetics
Coronavirus Infections / immunology
Coronavirus Infections / prevention & control*
Coronavirus Infections / virology
Disease Models, Animal
Genetic Vectors
Green Fluorescent Proteins / genetics
Host Microbial Interactions / immunology
Humans
Lung / immunology
Lung / pathology
Lung / virology
Mice
Mice, Inbred BALB C
Mice, Transgenic
Pandemics / prevention & control*
Peptidyl-Dipeptidase A / genetics
Pneumonia, Viral / immunology
Pneumonia, Viral / prevention & control*
Pneumonia, Viral / virology
Receptors, Virus / genetics
SARS-CoV-2
Translational Research, Biomedical
Vaccines, Synthetic / genetics
Vaccines, Synthetic / immunology
Vaccines, Synthetic / pharmacology
Vero Cells
Vesicular stomatitis Indiana virus / genetics*
Vesicular stomatitis Indiana virus / immunology
Viral Vaccines / genetics*
Viral Vaccines / immunology
Viral Vaccines / pharmacology

Substances

Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines
Receptors, Virus
Vaccines, Synthetic
Viral Vaccines
enhanced green fluorescent protein
Green Fluorescent Proteins
Peptidyl-Dipeptidase A
ACE2 protein, human
Ace2 protein, mouse
Angiotensin-Converting Enzyme 2

Abstract

Publication types

MeSH terms

Substances

Grants and funding