Scalable live-attenuated SARS-CoV-2 vaccine candidate demonstrates preclinical safety and efficacy

被引：103

作者：

Wang, Ying ^{[1
]}

Yang, Chen ^{[1
]}

Song, Yutong ^{[1
]}

Coleman, J. Robert ^{[1
]}

Stawowczyk, Marcin ^{[1
]}

Tafrova, Juliana ^{[1
]}

Tasker, Sybil ^{[1
]}

Boltz, David ^{[1
]}

Baker, Robert ^{[2
]}

Garcia, Liliana ^{[2
]}

Seale, Olivia ^{[2
]}

Kushnir, Anna ^{[1
]}

Wimmer, Eckard ^{[3
]}

Mueller, Steffen ^{[1
]}

机构：

[1] Codagenix Inc, Farmingdale, NY 11735 USA

[2] IIT, Div Microbiol & Mol Biol, Res Inst, Chicago, IL 60616 USA

[3] SUNY Stony Brook, Dept Microbiol & Immunol, Stony Brook, NY 11794 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2021年 / 118卷 / 29期

关键词：

vaccine; COVID-19; live attenuated; codon deoptimization; INFLUENZA-VIRUS; CODON; GENOME; INFECTION; FITNESS;

D O I：

10.1073/pnas.2102775118

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Successfully combating the COVID-19 pandemic depends on mass vaccination with suitable vaccines to achieve herd immunity. Here, we describe COVI-VAC, the only live attenuated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine currently in clinical development. COVI-VAC was developed by recoding a segment of the viral spike protein with synonymous suboptimal codon pairs (codon-pair deoptimization), thereby introducing 283 silent (point) mutations. In addition, the furin cleavage site within the spike protein was deleted from the viral genome for added safety of the vaccine strain. Except for the furin cleavage site deletion, the COVI-VAC and parental SARS-CoV-2 amino acid sequences are identical, ensuring that all viral proteins can engage with the host immune system of vaccine recipients. COVI-VAC was temperature sensitive in vitro yet grew robustly (>10(7) plaque forming units/mL) at the permissive temperature. Tissue viral loads were consistently lower, lung pathology milder, and weight loss reduced in Syrian golden hamsters (Mesocricetus auratus) vaccinated intranasally with COVI-VAC compared to those inoculated with wild-type (WT) virus. COVI-VAC inoculation generated spike IgG antibody levels and plaque reduction neutralization titers similar to those in hamsters inoculated with WT virus. Upon challenge with WT virus, COVI-VAC vaccination reduced lung challenge viral titers, resulted in undetectable virus in the brain, and protected hamsters from almost all SARS-CoV-2-associated weight loss. Highly attenuated COVI-VAC is protective at a single intranasal dose in a relevant in vivo model. This, coupled with its large-scale manufacturing potential, supports its potential use in mass vaccination programs.

引用

页数：7

共 38 条

[21] Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges [J].