tetano
Editor, Senior Moderator
Immunity
. 2021 Feb 4;S1074-7613(21)00042-X.
doi: 10.1016/j.immuni.2021.02.001. Online ahead of print.
A modified vaccinia Ankara vector-based vaccine protects macaques from SARS-CoV-2 infection, immune pathology, and dysfunction in the lungs
Nanda Kishore Routhu[SUP] 1 [/SUP], Narayanaiah Cheedarla[SUP] 1 [/SUP], Sailaja Gangadhara[SUP] 1 [/SUP], Venkata Satish Bollimpelli[SUP] 1 [/SUP], Arun K Boddapati[SUP] 2 [/SUP], Ayalnesh Shiferaw[SUP] 1 [/SUP], Sheikh Abdul Rahman[SUP] 1 [/SUP], Anusmita Sahoo[SUP] 1 [/SUP], Venkata Viswanadh Edara[SUP] 3 [/SUP], Lilin Lai[SUP] 3 [/SUP], Katharine Floyd[SUP] 3 [/SUP], Shelly Wang[SUP] 4 [/SUP], Stephanie Fischinger[SUP] 5 [/SUP], Caroline Atyeo[SUP] 5 [/SUP], Sally A Shin[SUP] 5 [/SUP], Sanjeev Gumber[SUP] 6 [/SUP], Shannon Kirejczyk[SUP] 6 [/SUP], Joyce Cohen[SUP] 7 [/SUP], Sherrie M Jean[SUP] 7 [/SUP], Jennifer S Wood[SUP] 7 [/SUP], Fawn Connor-Stroud[SUP] 7 [/SUP], Rachelle L Stammen[SUP] 7 [/SUP], Amit A Upadhyay[SUP] 4 [/SUP], Kathryn Pellegrini[SUP] 4 [/SUP], David Montefiori[SUP] 8 [/SUP], Pei-Yong Shi[SUP] 9 [/SUP], Vineet D Menachery[SUP] 10 [/SUP], Galit Alter[SUP] 5 [/SUP], Thomas H Vanderford[SUP] 4 [/SUP], Steven E Bosinger[SUP] 2 [/SUP], Mehul S Suthar[SUP] 3 [/SUP], Rama Rao Amara[SUP] 11 [/SUP]
Affiliations
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[SUP]+[/SUP] 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[SUP]+[/SUP] 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.
. 2021 Feb 4;S1074-7613(21)00042-X.
doi: 10.1016/j.immuni.2021.02.001. Online ahead of print.
A modified vaccinia Ankara vector-based vaccine protects macaques from SARS-CoV-2 infection, immune pathology, and dysfunction in the lungs
Nanda Kishore Routhu[SUP] 1 [/SUP], Narayanaiah Cheedarla[SUP] 1 [/SUP], Sailaja Gangadhara[SUP] 1 [/SUP], Venkata Satish Bollimpelli[SUP] 1 [/SUP], Arun K Boddapati[SUP] 2 [/SUP], Ayalnesh Shiferaw[SUP] 1 [/SUP], Sheikh Abdul Rahman[SUP] 1 [/SUP], Anusmita Sahoo[SUP] 1 [/SUP], Venkata Viswanadh Edara[SUP] 3 [/SUP], Lilin Lai[SUP] 3 [/SUP], Katharine Floyd[SUP] 3 [/SUP], Shelly Wang[SUP] 4 [/SUP], Stephanie Fischinger[SUP] 5 [/SUP], Caroline Atyeo[SUP] 5 [/SUP], Sally A Shin[SUP] 5 [/SUP], Sanjeev Gumber[SUP] 6 [/SUP], Shannon Kirejczyk[SUP] 6 [/SUP], Joyce Cohen[SUP] 7 [/SUP], Sherrie M Jean[SUP] 7 [/SUP], Jennifer S Wood[SUP] 7 [/SUP], Fawn Connor-Stroud[SUP] 7 [/SUP], Rachelle L Stammen[SUP] 7 [/SUP], Amit A Upadhyay[SUP] 4 [/SUP], Kathryn Pellegrini[SUP] 4 [/SUP], David Montefiori[SUP] 8 [/SUP], Pei-Yong Shi[SUP] 9 [/SUP], Vineet D Menachery[SUP] 10 [/SUP], Galit Alter[SUP] 5 [/SUP], Thomas H Vanderford[SUP] 4 [/SUP], Steven E Bosinger[SUP] 2 [/SUP], Mehul S Suthar[SUP] 3 [/SUP], Rama Rao Amara[SUP] 11 [/SUP]
Affiliations
- PMID: 33631118
- DOI: 10.1016/j.immuni.2021.02.001
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[SUP]+[/SUP] 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[SUP]+[/SUP] 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.