A self-amplifying mRNA COVID-19 vaccine drives potent and broad immune responses at low doses that protects non-human primates against SARS-CoV-2

Rappaport, A. R.; Hong, S.-J.; Scallan, C. D.; Gitlin, L.; Akoopie, A.; Boucher, G. R.; Egorova, M.; Espinosa, J. A.; Fidanza, M.; Kachura, M. A.; Shen, A.; Sivko, G.; Van Abbema, A.; Veres, R. L.; Jooss, K.

doi:10.1101/2021.11.08.467773

bioRxiv · 10.1101/2021.11.08.467773

A self-amplifying mRNA COVID-19 vaccine drives potent and broad immune responses at low doses that protects non-human primates against SARS-CoV-2

Rappaport, A. R.·Hong, S.-J.·Scallan, C. D.·Gitlin, L.·Akoopie, A.·Boucher, G. R.·Egorova, M.·Espinosa, J. A.·Fidanza, M.·Kachura, M. A.·Shen, A.·Sivko, G.·Van Abbema, A.·Veres, R. L.·Jooss, K.

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Abstract

The coronavirus disease 2019 (COVID-19) pandemic continues to spread globally, highlighting the urgent need for safe and effective vaccines that could be rapidly mobilized to immunize large populations. We report the preclinical development of a self-amplifying mRNA (SAM) vaccine encoding a prefusion stabilized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein and demonstrate potent cellular and humoral immune responses at low doses in mice and rhesus macaques. The homologous prime-boost vaccination regimen of SAM at 3, 10 and 30 g induced potent neutralizing antibody titers in rhesus macaques following two SAM vaccinations at all dose levels, with the 10 g dose generating geometric mean titers (GMT) 48-fold greater than the GMT of a panel of SARS-CoV-2 convalescent human sera. Spike-specific T cell responses were observed at all dose levels. SAM vaccination provided protective efficacy against SARS-CoV-2 challenge as both a homologous prime-boost and as a single boost following ChAd prime, demonstrating reduction of viral replication in both the upper and lower airways. Protection was most effective with a SAM prime-boost vaccination regimen at 10 and 30 g and with a ChAd/SAM heterologous prime-boost regimen. The SAM vaccine is currently being evaluated in clinical trials as both a homologous prime-boost regimen at low doses and as a boost following heterologous prime.

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Rappaport, A. R., Hong, S.-J., Scallan, C. D., Gitlin, L., Akoopie, A., Boucher, G. R., Egorova, M., Espinosa, J. A., Fidanza, M., Kachura, M. A., Shen, A., Sivko, G., Van Abbema, A., Veres, R. L., Jooss, K.. 2021-11-09. A self-amplifying mRNA COVID-19 vaccine drives potent and broad immune responses at low doses that protects non-human primates against SARS-CoV-2. https://doi.org/10.1101/2021.11.08.467773

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