A single dose of self-transcribing and replicating RNA-based SARS-CoV-2 vaccine produces protective adaptive immunity in mice
Ruklanthi de Alwis, Esther S. Gan, Shiwei Chen, Yan Shan Leong, Hwee Cheng Tan, Summer L. Zhang, Clement Yau, Jenny G. Low, Shirin Kalimuddin, Daiki Matsuda, Elizabeth Cheresh Allen, Paula Hartman, Kyoung‐Joo Jenny Park, Maher Alayyoubi, Hari Bhaskaran, Adrian Dukanovic, Yanjie Bao, Brenda Clemente, Jerel Vega, Scott Roberts, Jose A. Gonzalez, Marciano Sablad, Rodrigo Yelin, Wendy Taylor, Kiyoshi Tachikawa, Suezanne E. Parker, Priya Karmali, Jared Davis, Brian M. Sullivan, Sean M. Sullivan, Steve Hughes, Pad Chivukula, Eng Eong Ooi
Abstract
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 prolongs 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 interferon (IFN)γ and interleukin-4 (IL-4)-positive CD4 + T helper (Th) lymphocytes as well as anti-spike glycoprotein immunoglobulin G (IgG)2a/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.