PT  - JOURNAL ARTICLE
AU  - Nanda Kishore Routhu
AU  - Sailaja Gangadhara
AU  - Narayanaiah Cheedarla
AU  - Ayalnesh Shiferaw
AU  - Sheikh Abdul Rahman
AU  - Anusmita Sahoo
AU  - Pei-Yong Shi
AU  - Vineet D. Menachery
AU  - Katharine Floyd
AU  - Stephanie Fischinger
AU  - Caroline Atyeo
AU  - Galit Alter
AU  - Mehul S. Suthar
AU  - Rama Rao Amara
TI  - Modified Vaccinia Ankara Based SARS-CoV-2 Vaccine Expressing Full-Length Spike Induces Strong Neutralizing Antibody Response
AID  - 10.1101/2020.06.27.175166
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.06.27.175166
4099  - http://biorxiv.org/content/early/2020/06/27/2020.06.27.175166.short
4100  - http://biorxiv.org/content/early/2020/06/27/2020.06.27.175166.full
AB  - 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.