tetano
Editor, Senior Moderator
Mol Ther
. 2021 Apr 3;S1525-0016(21)00188-X.
doi: 10.1016/j.ymthe.2021.04.001. Online ahead of print.
A Single Dose of Self-Transcribing and Replicating RNA Based SARS-CoV-2 Vaccine Produces Protective Adaptive Immunity In Mice
Ruklanthi de Alwis[SUP] 1 [/SUP], Esther S Gan[SUP] 2 [/SUP], Shiwei Chen[SUP] 2 [/SUP], Yan Shan Leong[SUP] 3 [/SUP], Hwee Cheng Tan[SUP] 2 [/SUP], Summer L Zhang[SUP] 2 [/SUP], Clement Yau[SUP] 2 [/SUP], Jenny G H Low[SUP] 4 [/SUP], Shirin Kalimuddin[SUP] 5 [/SUP], Daiki Matsuda[SUP] 6 [/SUP], Elizabeth C Allen[SUP] 6 [/SUP], Paula Hartman[SUP] 6 [/SUP], Jenny Park[SUP] 6 [/SUP], Maher Alayyoubi[SUP] 6 [/SUP], Hari Bhaskaran[SUP] 6 [/SUP], Adrian Dukanovic[SUP] 6 [/SUP], Yanjie Bao[SUP] 6 [/SUP], Brenda Clemente[SUP] 6 [/SUP], Jerel Vega[SUP] 6 [/SUP], Scott Roberts[SUP] 6 [/SUP], Jose A Gonzalez[SUP] 6 [/SUP], Marciano Sablad[SUP] 6 [/SUP], Rodrigo Yelin[SUP] 6 [/SUP], Wendy Taylor[SUP] 6 [/SUP], Kiyoshi Tachikawa[SUP] 6 [/SUP], Suezanne Parker[SUP] 6 [/SUP], Priya Karmali[SUP] 6 [/SUP], Jared Davis[SUP] 6 [/SUP], Sean M Sullivan[SUP] 7 [/SUP], Steve G Hughes[SUP] 6 [/SUP], Pad Chivukula[SUP] 6 [/SUP], Eng Eong Ooi[SUP] 1 [/SUP]
Affiliations
Abstract
A self-transcribing and replicating RNA (STARR[SUP]TM[/SUP]) 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[SUP]+[/SUP] T lymphocyte response. Assaying for intracellular cytokine staining for IFN-? and IL-4 positive CD4[SUP]+[/SUP] 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 ?g and 10 ?g 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.
Keywords: COVID-19; Coronavirus; LUNAR?-COV19; SARS-CoV-2; STARRTM; Vaccine; conventional mRNA; self-amplifying RNA.
. 2021 Apr 3;S1525-0016(21)00188-X.
doi: 10.1016/j.ymthe.2021.04.001. Online ahead of print.
A Single Dose of Self-Transcribing and Replicating RNA Based SARS-CoV-2 Vaccine Produces Protective Adaptive Immunity In Mice
Ruklanthi de Alwis[SUP] 1 [/SUP], Esther S Gan[SUP] 2 [/SUP], Shiwei Chen[SUP] 2 [/SUP], Yan Shan Leong[SUP] 3 [/SUP], Hwee Cheng Tan[SUP] 2 [/SUP], Summer L Zhang[SUP] 2 [/SUP], Clement Yau[SUP] 2 [/SUP], Jenny G H Low[SUP] 4 [/SUP], Shirin Kalimuddin[SUP] 5 [/SUP], Daiki Matsuda[SUP] 6 [/SUP], Elizabeth C Allen[SUP] 6 [/SUP], Paula Hartman[SUP] 6 [/SUP], Jenny Park[SUP] 6 [/SUP], Maher Alayyoubi[SUP] 6 [/SUP], Hari Bhaskaran[SUP] 6 [/SUP], Adrian Dukanovic[SUP] 6 [/SUP], Yanjie Bao[SUP] 6 [/SUP], Brenda Clemente[SUP] 6 [/SUP], Jerel Vega[SUP] 6 [/SUP], Scott Roberts[SUP] 6 [/SUP], Jose A Gonzalez[SUP] 6 [/SUP], Marciano Sablad[SUP] 6 [/SUP], Rodrigo Yelin[SUP] 6 [/SUP], Wendy Taylor[SUP] 6 [/SUP], Kiyoshi Tachikawa[SUP] 6 [/SUP], Suezanne Parker[SUP] 6 [/SUP], Priya Karmali[SUP] 6 [/SUP], Jared Davis[SUP] 6 [/SUP], Sean M Sullivan[SUP] 7 [/SUP], Steve G Hughes[SUP] 6 [/SUP], Pad Chivukula[SUP] 6 [/SUP], Eng Eong Ooi[SUP] 1 [/SUP]
Affiliations
- PMID: 33823303
- DOI: 10.1016/j.ymthe.2021.04.001
Abstract
A self-transcribing and replicating RNA (STARR[SUP]TM[/SUP]) 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[SUP]+[/SUP] T lymphocyte response. Assaying for intracellular cytokine staining for IFN-? and IL-4 positive CD4[SUP]+[/SUP] 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 ?g and 10 ?g 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.
Keywords: COVID-19; Coronavirus; LUNAR?-COV19; SARS-CoV-2; STARRTM; Vaccine; conventional mRNA; self-amplifying RNA.