A Single Dose of Self-Transcribing and Replicating RNA Based SARS-CoV-2 Vaccine Produces Protective Adaptive Immunity In Mice

de Alwis, Ruklanthi; Gan, Esther S; Chen, Shiwei; Leong, Yan Shan; Tan, Hwee Cheng; Zhang, Summer L; Yau, Clement; Matsuda, Daiki; Allen, Elizabeth; Hartman, Paula; Park, Jenny; Alayyoubi, Maher; Bhaskaran, Hari; Dukanovic, Adrian; Bao, Belle; Clemente, Brenda; Vega, Jerel; Roberts, Scott; Gonzalez, Jose A.; Sablad, Marciano; Yelin, Rodrigo; Taylor, Wendy; Tachikawa, Kiyoshi; Parker, Suezanne; Karmali, Priya; Davis, Jared; Sullivan, Sean M.; Hughes, Steve G.; Chivukula, Pad; Ooi, Eng Eong

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.