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

• Published in: Immunity (Cambridge, Mass.) Vol. 54; no. 3; pp. 542 - 556.e9
• Main Authors: Routhu, Nanda Kishore, Cheedarla, Narayanaiah, Gangadhara, Sailaja, Bollimpelli, Venkata Satish, Boddapati, Arun K., Shiferaw, Ayalnesh, Rahman, Sheikh Abdul, Sahoo, Anusmita, Edara, Venkata Viswanadh, Lai, Lilin, Floyd, Katharine, Wang, Shelly, Fischinger, Stephanie, Atyeo, Caroline, Shin, Sally A., Gumber, Sanjeev, Kirejczyk, Shannon, Cohen, Joyce, Jean, Sherrie M., Wood, Jennifer S., Connor-Stroud, Fawn, Stammen, Rachelle L., Upadhyay, Amit A., Pellegrini, Kathryn, Montefiori, David, Shi, Pei-Yong, Menachery, Vineet D., Alter, Galit, Vanderford, Thomas H., Bosinger, Steven E., Suthar, Mehul S., Amara, Rama Rao
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09-03-2021; Elsevier Limited
• Subjects: Abnormalities; Adenoviruses; Amino acids; Animals; Antibodies; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Antigens, Viral - genetics; Antigens, Viral - immunology; CD8 antigen; CD8 T cells; Coronaviruses; COVID-19; 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; Gene sequencing; Genetic Vectors - genetics; Immunophenotyping; Infections; Inflammation; Interferon; Lung - immunology; Lung - pathology; Lung - virology; Lungs; Lymphocytes; Lymphocytes T; Macaca; Macrophages, Alveolar - immunology; Macrophages, Alveolar - metabolism; Macrophages, Alveolar - pathology; Membrane fusion; Mice; Middle East respiratory syndrome; Modified Vaccinia Ankara; Mutation; Neutralizing; Neutralizing antibody; Pandemics; Protection; Proteins; Respiration; Respiratory diseases; Rhesus macaques; SARS-CoV-2; SARS-CoV-2 - immunology; Sequence analysis; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Spike; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - immunology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Trachea; Vaccination; Vaccination - methods; Vaccine; Vaccines; Vaccines, DNA - genetics; Vaccines, DNA - immunology; Vaccinia; Vaccinia virus - genetics; Viral diseases; Viral infections; Viruses; Ankara Turkey; Turkey; Spike; COVID-19; SARS-CoV-2; Modified Vaccinia Ankara; Rhesus macaques; Vaccine; Protection; Neutralizing antibody; CD8 T cells
• ISSN: 1074-7613; 1097-4180; 1097-4180
• DOI: 10.1016/j.immuni.2021.02.001

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.
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•Generated MVA-based COVID-19 vaccine encoding prefusion-stabilized spike (MVA/S)•MVA/S vaccination induces strong nAb response and CD8+ T cell response in macaques•MVA/S vaccine protects macaques from SARS-CoV-2 infection and lung immunopathology•MVA/S vaccine prevents infection-induced inflammation and B cell abnormalities in lungs
Modified vaccinia Ankara (MVA) vector-based vaccines are attractive because of their excellent safety and ability to induce long-lived humoral and cellular immunity in humans. Routhu et al. show that an MVA-based COVID-19 vaccine encoding prefusion-stabilized spike (MVA/S) induces strong neutralizing antibody and CD8+ T cell responses and protects macaques from SARS-CoV2 infection, immunopathology, and infection-induced B cell abnormalities in the lungs.