A modified vaccinia Ankara vector-based vaccine protects macaques from SARS-CoV-2 infection, immune pathology, and dysfunction in the lungs

Nanda Kishore Routhu; Narayanaiah Cheedarla; Sailaja Gangadhara; Venkata Satish Bollimpelli; Arun K Boddapati; Ayalnesh Shiferaw; Sheikh Abdul Rahman; Anusmita Sahoo; Venkata Viswanadh Edara; Lilin Lai; Katharine Floyd; Shelly Wang; Stephanie Fischinger; Caroline Atyeo; Sally A Shin; Sanjeev Gumber; Shannon Kirejczyk; Joyce Cohen; Sherrie M Jean; Jennifer S Wood; Fawn Connor-Stroud; Rachelle L Stammen; Amit A Upadhyay; Kathryn Pellegrini; David Montefiori; Pei-Yong Shi; Vineet D Menachery; Galit Alter; Thomas H Vanderford; Steven E Bosinger; Mehul S Suthar; Rama Rao Amara

doi:10.1016/j.immuni.2021.02.001

A modified vaccinia Ankara vector-based vaccine protects macaques from SARS-CoV-2 infection, immune pathology, and dysfunction in the lungs

Immunity. 2021 Mar 9;54(3):542-556.e9. doi: 10.1016/j.immuni.2021.02.001. Epub 2021 Feb 4.

Authors

Nanda Kishore Routhu¹, Narayanaiah Cheedarla¹, Sailaja Gangadhara¹, Venkata Satish Bollimpelli¹, Arun K Boddapati², Ayalnesh Shiferaw¹, Sheikh Abdul Rahman¹, Anusmita Sahoo¹, Venkata Viswanadh Edara³, Lilin Lai³, Katharine Floyd³, Shelly Wang⁴, Stephanie Fischinger⁵, Caroline Atyeo⁵, Sally A Shin⁵, Sanjeev Gumber⁶, Shannon Kirejczyk⁶, Joyce Cohen⁷, Sherrie M Jean⁷, Jennifer S Wood⁷, Fawn Connor-Stroud⁷, Rachelle L Stammen⁷, Amit A Upadhyay⁴, Kathryn Pellegrini⁴, David Montefiori⁸, Pei-Yong Shi⁹, Vineet D Menachery¹⁰, Galit Alter⁵, Thomas H Vanderford⁴, Steven E Bosinger², Mehul S Suthar³, Rama Rao Amara¹¹

Affiliations

¹ Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA.
² Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Pathology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA.
³ Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA.
⁴ Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
⁵ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
⁶ Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
⁷ Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
⁸ Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
⁹ Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX, USA.
¹⁰ Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX, USA.
¹¹ Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA. Electronic address: ramara@emory.edu.

Abstract

A combination of vaccination approaches will likely be necessary to fully control the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Here, we show that modified vaccinia Ankara (MVA) vectors expressing membrane-anchored pre-fusion stabilized spike (MVA/S) but not secreted S1 induced strong neutralizing antibody responses against SARS-CoV-2 in mice. In macaques, the MVA/S vaccination induced strong neutralizing antibodies and CD8⁺ T cell responses, and conferred protection from SARS-CoV-2 infection and virus replication in the lungs as early as day 2 following intranasal and intratracheal challenge. Single-cell RNA sequencing analysis of lung cells on day 4 after infection revealed that MVA/S vaccination also protected macaques from infection-induced inflammation and B cell abnormalities and lowered induction of interferon-stimulated genes. These results demonstrate that MVA/S vaccination induces neutralizing antibodies and CD8⁺ T cells in the blood and lungs and is a potential vaccine candidate for SARS-CoV-2.

Keywords: CD8 T cells; COVID-19; Modified Vaccinia Ankara; Neutralizing antibody; Protection; Rhesus macaques; SARS-CoV-2; Spike; Vaccine.

Publication types

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

MeSH terms

Animals
Antibodies, Neutralizing / immunology
Antibodies, Viral / immunology
Antigens, Viral / genetics
Antigens, Viral / immunology
COVID-19 / immunology
COVID-19 / pathology
COVID-19 / prevention & control*
COVID-19 / virology
COVID-19 Vaccines / genetics
COVID-19 Vaccines / immunology*
Disease Models, Animal
Gene Expression
Gene Order
Genetic Vectors / genetics*
Immunophenotyping
Lung / immunology
Lung / pathology
Lung / virology
Macaca
Macrophages, Alveolar / immunology
Macrophages, Alveolar / metabolism
Macrophages, Alveolar / pathology
Mice
SARS-CoV-2 / immunology*
Spike Glycoprotein, Coronavirus / genetics
Spike Glycoprotein, Coronavirus / immunology
T-Lymphocyte Subsets / immunology
T-Lymphocyte Subsets / metabolism
Vaccination / methods
Vaccines, DNA / genetics
Vaccines, DNA / immunology*
Vaccinia virus / genetics*

Substances

Antibodies, Neutralizing
Antibodies, Viral
Antigens, Viral
COVID-19 Vaccines
Spike Glycoprotein, Coronavirus
Vaccines, DNA
spike protein, SARS-CoV-2

Abstract

Publication types

MeSH terms

Substances

Grants and funding