A single dose of self-transcribing and replicating RNA-based SARS-CoV-2 vaccine produces protective adaptive immunity in mice

被引：124

作者：

de Alwis, Ruklanthi ^{[1
,2
]}

Gan, Esther S. ^{[2
]}

Chen, Shiwei ^{[2
]}

Leong, Yan Shan ^{[1
]}

Tan, Hwee Cheng ^{[2
]}

Zhang, Summer L. ^{[2
]}

Yau, Clement ^{[2
]}

Low, Jenny G. H. ^{[1
,2
,3
]}

Kalimuddin, Shirin ^{[2
,3
]}

Matsuda, Daiki ^{[4
]}

Allen, Elizabeth C. ^{[4
]}

Hartman, Paula ^{[4
]}

Park, Kyoung-Joo Jenny ^{[4
]}

Alayyoubi, Maher ^{[4
]}

Bhaskaran, Hari ^{[4
]}

Dukanovic, Adrian ^{[4
]}

Bao, Yanjie ^{[4
]}

Clemente, Brenda ^{[4
]}

Vega, Jerel ^{[4
]}

Roberts, Scott ^{[4
]}

Gonzalez, Jose A. ^{[4
]}

Sablad, Marciano ^{[4
]}

Yelin, Rodrigo ^{[4
]}

Taylor, Wendy ^{[4
]}

Tachikawa, Kiyoshi ^{[4
]}

Parker, Suezanne ^{[4
]}

Karmali, Priya ^{[4
]}

Davis, Jared ^{[4
]}

Sullivan, Brian M. ^{[4
]}

Sullivan, Sean M. ^{[4
]}

Hughes, Steve G. ^{[4
]}

Chivukula, Pad ^{[4
]}

Ooi, Eng Eong ^{[1
,2
]}

机构：

[1] SingHlth Duke NUS Acad Med Ctr, Viral Res & Expt Med Ctr, Singapore, Singapore

[2] Duke NUS Med Sch, Program Emerging Infect Dis, Singapore, Singapore

[3] Singapore Gen Hosp, Dept Infect Dis, Singapore, Singapore

[4] Arcturus Therapeut Inc, 10628 Sci Ctr Dr, San Diego, CA 92121 USA

来源：

MOLECULAR THERAPY | 2021年 / 29卷 / 06期

基金：

英国医学研究理事会;

关键词：

MESSENGER-RNA; INFECTION; RESPONSES;

D O I：

10.1016/j.ymthe.2021.04.001

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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)gamma 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 mu g and 10 mu 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.

引用

页码：1970 / 1983

页数：14

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