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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
Immunity (Cambridge, Mass.), 03/2021, Letnik: 54, Številka: 3Journal Article
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. Display omitted •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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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