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Correspondence: Rama Rao Amara

Author contributions: 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.

Acknowledgements: 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.

Disclosures: 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.

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Research Funding:

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.

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.).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • Antibody response
  • Mucosal challenge
  • High-throughput
  • Immunogenicity
  • HIV-1
  • Antigen
  • Spike
  • MVA
  • DNA

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

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Journal Title:

Immunity

Volume:

Volume 54, Number 3

Publisher:

, Pages 542-+

Type of Work:

Article | Final Publisher PDF

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.

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© 2021 Elsevier Inc.

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