RT Journal Article
SR Electronic
T1 A Single Dose of Self-Transcribing and Replicating RNA Based SARS-CoV-2 Vaccine Produces Protective Adaptive Immunity In Mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.09.03.280446
DO 10.1101/2020.09.03.280446
A1 Ruklanthi de Alwis
A1 Esther S Gan
A1 Shiwei Chen
A1 Yan Shan Leong
A1 Hwee Cheng Tan
A1 Summer L Zhang
A1 Clement Yau
A1 Daiki Matsuda
A1 Elizabeth Allen
A1 Paula Hartman
A1 Jenny Park
A1 Maher Alayyoubi
A1 Hari Bhaskaran
A1 Adrian Dukanovic
A1 Belle Bao
A1 Brenda Clemente
A1 Jerel Vega
A1 Scott Roberts
A1 Jose A. Gonzalez
A1 Marciano Sablad
A1 Rodrigo Yelin
A1 Wendy Taylor
A1 Kiyoshi Tachikawa
A1 Suezanne Parker
A1 Priya Karmali
A1 Jared Davis
A1 Sean M. Sullivan
A1 Steve G. Hughes
A1 Pad Chivukula
A1 Eng Eong Ooi
YR 2020
UL http://biorxiv.org/content/early/2020/09/03/2020.09.03.280446.abstract
AB A self-transcribing and replicating RNA (STARR™) based vaccine (LUNAR®-COV19) has been developed to prevent SARS-CoV-2 infection. The vaccine encodes an alphavirus-based replicon and the SARS-CoV-2 full length spike glycoprotein. Translation of the replicon produces a replicase complex that amplifies and prolong SARS-CoV-2 spike glycoprotein expression. A single prime vaccination in mice led to robust antibody responses, with neutralizing antibody titers increasing up to day 60. Activation of cell mediated immunity produced a strong viral antigen specific CD8+ T lymphocyte response. Assaying for intracellular cytokine staining for IFN-γ and IL-4 positive CD4+ T helper lymphocytes as well as anti-spike glycoprotein IgG2a/IgG1 ratios supported a strong Th1 dominant immune response. Finally, single LUNAR-COV19 vaccination at both 2 μg and 10 μg doses completely protected human ACE2 transgenic mice from both mortality and even measurable infection following wild-type SARS-CoV-2 challenge. Our findings collectively suggest the potential of Lunar-COV19 as a single dose vaccine.Competing Interest StatementDaiki Matsuda, Elizabeth Allen, Paula Hartma3, Jenny Park, Maher Alayyoubi, Hari Bhaskaran, Adrian Dukanovic, Belle Bao, Brenda Clemente, Jerel Vega, Scott Roberts, Jose A. Gonzalez, Marciano Sablad, Rodrigo Yelin, Wendy Taylor, Kiyoshi Tachikawa, Suezanne Parker, Priya Karmali, Jared Davis, Sean M. Sullivan, Steve G. Hughes, Pad Chivukula are salaried employees of Arcturus Therapeutics, Inc. San Diego CA