TY - JOUR
T1 - A modified vaccinia Ankara vector-based vaccine protects macaques from SARS-CoV-2 infection, immune pathology, and dysfunction in the lungs
AU - Routhu, Nanda Kishore
AU - Cheedarla, Narayanaiah
AU - Gangadhara, Sailaja
AU - Bollimpelli, Venkata Satish
AU - Boddapati, Arun K.
AU - Shiferaw, Ayalnesh
AU - Rahman, Sheikh Abdul
AU - Sahoo, Anusmita
AU - Edara, Venkata Viswanadh
AU - Lai, Lilin
AU - Floyd, Katharine
AU - Wang, Shelly
AU - Fischinger, Stephanie
AU - Atyeo, Caroline
AU - Shin, Sally A.
AU - Gumber, Sanjeev
AU - Kirejczyk, Shannon
AU - Cohen, Joyce
AU - Jean, Sherrie M.
AU - Wood, Jennifer S.
AU - Connor-Stroud, Fawn
AU - Stammen, Rachelle L.
AU - Upadhyay, Amit A.
AU - Pellegrini, Kathryn
AU - Montefiori, David
AU - Shi, Pei Yong
AU - Menachery, Vineet D.
AU - Alter, Galit
AU - Vanderford, Thomas H.
AU - Bosinger, Steven E.
AU - Suthar, Mehul S.
AU - Amara, Rama Rao
N1 - Funding Information:
We thank Traci H. Legere, Brenda Wehrle, and Zeba S. Momin for help with processing blood and tissue samples, Drs. Bernard Moss and Lynda Wyatt for providing the pLW73 transfer plasmid, the Yerkes Division of Pathology and Research Resources for outstanding animal care during the pandemic, and the Histology and Molecular Pathology Lab for help with tissue sectioning. The following reagent was produced under HHSN272201400008C and obtained through BEI Resources, NIAID, NIH: vector pCAGGS containing the SARS-related coronavirus 2, Wuhan-Hu-1 spike glycoprotein RBD, NR-52309. Imaging for this research project was supported in part by the Emory University Integrated Cellular Imaging Microscopy Core. The content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institute of Health. This work was supported in part by National Institutes of Health grant RO1 AI148378-01S1 and Fast Grants award 2166 (to R.R.A.) and NCRR/NIH base grant P51 OD011132 to YNPRC. Next-generation sequencing services were provided by the Yerkes NHP Genomics Core, which is supported in part by NIH P51 OD011132 . Sequencing data were acquired on an Illumina NovaSeq6000 funded by NIH S10 OD026799 (to S.E.B.).
Funding Information:
We thank Traci H. Legere, Brenda Wehrle, and Zeba S. Momin for help with processing blood and tissue samples, Drs. Bernard Moss and Lynda Wyatt for providing the pLW73 transfer plasmid, the Yerkes Division of Pathology and Research Resources for outstanding animal care during the pandemic, and the Histology and Molecular Pathology Lab for help with tissue sectioning. The following reagent was produced under HHSN272201400008C and obtained through BEI Resources, NIAID, NIH: vector pCAGGS containing the SARS-related coronavirus 2, Wuhan-Hu-1 spike glycoprotein RBD, NR-52309. Imaging for this research project was supported in part by the Emory University Integrated Cellular Imaging Microscopy Core. The content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institute of Health. This work was supported in part by National Institutes of Health grant RO1 AI148378-01S1 and Fast Grants award 2166 (to R.R.A.) and NCRR/NIH base grant P51 OD011132 to YNPRC. Next-generation sequencing services were provided by the Yerkes NHP Genomics Core, which is supported in part by NIH P51 OD011132. Sequencing data were acquired on an Illumina NovaSeq6000 funded by NIH S10 OD026799 (to S.E.B.). R.R.A. was responsible for the overall experimental design and supervision of laboratory studies and manuscript writing and editing. Sailaja Gangadhara developed, constructed, and characterized the rMVA/S and MVA/S1 vaccines and provided vaccine stocks for animal studies. N.K.R. Sailaja Gangadhara, N.C. Ayalnesh Shiferaw, V.S.B. A.K.B. S.A.R. Anusmita Sahoo, V.V.E. L.L. K.F. S.W. S.F. C.A. A.A.U. and K.P. were responsible for conducting experiments, data collection, and data analysis. M.S.S. conducted and supervised live virus neutralizing antibody assays. D.M. supervised pseudovirus neutralizing antibody assays. J.C. S.M.J. J.S.W. F.C.-S. and R.L.S. provided veterinary support in ABSL-3. G.A. supervised the Luminex assays. S.E.B. supervised the single-cell RNA-seq analyses. T.H.V. supervised the viral RNA measurements. Sanjeev Gumber and S.K. performed H&E staining and determined lung pathology scores. P.-Y.S. and V.D.M. provided virus for neutralization assays and challenge studies. All authors contributed to manuscript writing and editing. R.R.A. Sailaja Gangadhara, and N.K.R. are co-inventors of the MVA/S vaccine technology. Emory University filed a patent on this technology. R.R.A. serves as a SAB member for Heat Biologics Inc.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/3/9
Y1 - 2021/3/9
N2 - 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.
AB - 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.
KW - CD8 T cells
KW - COVID-19
KW - Modified Vaccinia Ankara
KW - Neutralizing antibody
KW - Protection
KW - Rhesus macaques
KW - SARS-CoV-2
KW - Spike
KW - Vaccine
UR - http://www.scopus.com/inward/record.url?scp=85101565118&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85101565118&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2021.02.001
DO - 10.1016/j.immuni.2021.02.001
M3 - Article
C2 - 33631118
AN - SCOPUS:85101565118
SN - 1074-7613
VL - 54
SP - 542-556.e9
JO - Immunity
JF - Immunity
IS - 3
ER -