@article {Routhu2020.06.27.175166, author = {Nanda Kishore Routhu and Sailaja Gangadhara and Narayanaiah Cheedarla and Ayalnesh Shiferaw and Sheikh Abdul Rahman and Anusmita Sahoo and Pei-Yong Shi and Vineet D. Menachery and Katharine Floyd and Stephanie Fischinger and Caroline Atyeo and Galit Alter and Mehul S. Suthar and Rama Rao Amara}, title = {Modified Vaccinia Ankara Based SARS-CoV-2 Vaccine Expressing Full-Length Spike Induces Strong Neutralizing Antibody Response}, elocation-id = {2020.06.27.175166}, year = {2020}, doi = {10.1101/2020.06.27.175166}, publisher = {Cold Spring Harbor Laboratory}, abstract = {There is a great need for the development of vaccines for preventing SARS-CoV-2 infection and mitigating the COVID-19 pandemic. Here, we developed two modified vaccinia Ankara (MVA) based vaccines which express either a membrane anchored full-length spike protein (MVA/S) stabilized in a prefusion state or the S1 region of the spike (MVA/S1) which forms trimers and is secreted. Both immunogens contained the receptor-binding domain (RBD) which is a known target of antibody-mediated neutralization. Following immunizations with MVA/S or MVA/S1, both spike protein recombinants induced strong IgG antibodies to purified full-length SARS-CoV-2 spike protein. The MVA/S induced a robust antibody response to purified RBD, S1 and S2 whereas MVA/S1 induced an antibody response to the S1 region outside of the RBD region. Both vaccines induced an antibody response in the lung and that was associated with induction of bronchus-associated lymphoid tissue. MVA/S but not MVA/S1 vaccinated mice generated robust neutralizing antibody responses against SARS-CoV-2 that strongly correlated with RBD antibody binding titers. Mechanistically, S1 binding to ACE-2 was strong but reduced following prolonged pre-incubation at room temperature suggesting confirmation changes in RBD with time. These results demonstrate MVA/S is a potential vaccine candidate against SARS-CoV-2 infection.Competing Interest StatementThe authors have declared no competing interest.}, URL = {https://www.biorxiv.org/content/early/2020/06/27/2020.06.27.175166}, eprint = {https://www.biorxiv.org/content/early/2020/06/27/2020.06.27.175166.full.pdf}, journal = {bioRxiv} }