Transient acquisition of cross-species infectivity during the evolution of SARS-CoV-2

Chen, Qi; Huang, Xing‐Yao; Sun, Mengxu; Li, Rui-Ting; Gu, Huiying; Tian, Ying; Zhang, Rongrong; Luo, Dan; Zhou, Chao; Zhang, Yifei; Cao, Tian-Shu; Zhang, Nana; Deng, Yong-Qiang; Li, Xiaofeng; Qin, Cheng‐Feng

doi:10.1093/nsr/nwab167

Cited by 20 publications

(28 citation statements)

References 10 publications

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“…The emergence and spread of SARS-CoV-2 variants has arose global concerns due to enhanced transmissibility and reduced susceptibility to medical countermeasures. 19 Therefore, we further evaluated the in vivo protection efficacy of the mRNA-HB27-LNP against the SARS-CoV-2 Beta variant in an established animal model (Fig. 2e ).…”

Section: Resultsmentioning

confidence: 99%

“…2e ). 19 Briefly, groups of 8-month-old female BALB/c mice received i.v. administration of 1 mg/kg of mRNA-HB27-LNP or placebo, then, all mice were i.n.…”

Section: Resultsmentioning

confidence: 99%

“…The SARS-CoV-2 Beta variant was isolated from an imported patient from South Africa and Stored at National Pathogen Resource Center (NPRC), China. 19 These viruses were amplified and titrated by standard plaque forming assay on Vero cells. The production and purification of HB27 in CHO cells were performed by SinoCell Tech.…”

Section: Methodsmentioning

confidence: 99%

“…The in vivo prophylactic efficacy of mRNA-HB27-LNP was assessed by using the well-established mouse model based on a SARS-CoV-2 mouse adapted strain MASCp36 17 and Beta variant strain, 19 respectively. For MASCp36 model, groups of 8-month-old female BALB/c mice ( n = 32) were i.v.…”

Section: Methodsmentioning

confidence: 99%

“…Viral burden in lung from mice and hamster were measured as described previously. 19 Briefly, lung tissue homogenates were clarified by centrifugation at 6000 rpm for 6 min and viral RNA was extracted using the QIAamp Viral RNA Mini Kit (Qiagen) according to the manufacturer’s protocol. Viral sgRNA quantification in each tissue sample was performed by RT-qPCR targeting the S gene of SARS-CoV-2.…”

Section: Methodsmentioning

confidence: 99%

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Lipid nanoparticle-encapsulated mRNA antibody provides long-term protection against SARS-CoV-2 in mice and hamsters

Deng

Zhang

et al. 2022

Cell Res

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Monoclonal antibodies represent important weapons in our arsenal to against the COVID-19 pandemic. However, this potential is severely limited by the time-consuming process of developing effective antibodies and the relative high cost of manufacturing. Herein, we present a rapid and cost-effective lipid nanoparticle (LNP) encapsulated-mRNA platform for in vivo delivery of SARS-CoV-2 neutralization antibodies. Two mRNAs encoding the light and heavy chains of a potent SARS-CoV-2 neutralizing antibody HB27, which is currently being evaluated in clinical trials, were encapsulated into clinical grade LNP formulations (named as mRNA-HB27-LNP). In vivo characterization demonstrated that intravenous administration of mRNA-HB27-LNP in mice resulted in a longer circulating half-life compared with the original HB27 antibody in protein format. More importantly, a single prophylactic administration of mRNA-HB27-LNP provided protection against SARS-CoV-2 challenge in mice at 1, 7 and even 63 days post administration. In a close contact transmission model, prophylactic administration of mRNA-HB27-LNP prevented SARS-CoV-2 infection between hamsters in a dose-dependent manner. Overall, our results demonstrate a superior long-term protection against SARS-CoV-2 conferred by a single administration of this unique mRNA antibody, highlighting the potential of this universal platform for antibody-based disease prevention and therapy against COVID-19 as well as a variety of other infectious diseases.

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Section: Resultsmentioning

confidence: 99%

“…2e ). 19 Briefly, groups of 8-month-old female BALB/c mice received i.v. administration of 1 mg/kg of mRNA-HB27-LNP or placebo, then, all mice were i.n.…”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Lipid nanoparticle-encapsulated mRNA antibody provides long-term protection against SARS-CoV-2 in mice and hamsters

Deng

Zhang

et al. 2022

Cell Res

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Comparative characterization of SARS‐CoV‐2 variants of concern and mouse‐adapted strains in mice

Chen

Huang

Liu

et al. 2022

Journal of Medical Virology

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SARS‐CoV‐2 has evolved into a panel of variants of concern (VOCs) and constituted a sustained threat to global health. The wildtype (WT) SARS‐CoV‐2 isolates fail to infect mice, while the Beta variant, one of the VOCs, has acquired the capability to infect standard laboratory mice, raising a spreading risk of SARS‐CoV‐2 from humans to mice. However, the infectivity and pathogenicity of other VOCs in mice remain not fully understood. In this study, we systematically investigated the infectivity and pathogenicity of three VOCs, Alpha, Beta, and Delta, in mice in comparison with two well‐understood SARS‐CoV‐2 mouse‐adapted strains, MASCp6 and MASCp36, sharing key mutations in the receptor‐binding domain (RBD) with Alpha or Beta, respectively. Our results showed that the Beta variant had the strongest infectivity and pathogenicity among the three VOCs, while the Delta variant only caused limited replication and mild pathogenic changes in the mouse lung, which is much weaker than what the Alpha variant did. Meanwhile, Alpha showed comparable infectivity in lungs in comparison with MASCp6, and Beta only showed slightly lower infectivity in lungs when compared with MASCp36. These results indicated that all three VOCs have acquired the capability to infect mice, highlighting the ongoing spillover risk of SARS‐CoV‐2 from humans to mice during the continued evolution of SARS‐CoV‐2, and that the key amino acid mutations in the RBD of mouse‐adapted strains may be referenced as an early‐warning indicator for predicting the spillover risk of newly emerging SARS‐CoV‐2 variants.

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Competitive fitness and homologous recombination of SARS‐CoV‐2 variants of concern

Chen,

Qin,

Zhou

et al. 2023

Journal of Medical Virology

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Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) variants continue to emerge and cocirculate in humans and wild animals. The factors driving the emergence and replacement of novel variants and recombinants remain incompletely understood. Herein, we comprehensively characterized the competitive fitness of SARS‐CoV‐2 wild type (WT) and three variants of concern (VOCs), Alpha, Beta and Delta, by coinfection and serial passaging assays in different susceptible cells. Deep sequencing analyses revealed cell‐specific competitive fitness: the Beta variant showed enhanced replication fitness during serial passage in Caco‐2 cells, whereas the WT and Alpha variant showed elevated fitness in Vero E6 cells. Interestingly, a high level of neutralizing antibody sped up competition and completely reshaped the fitness advantages of different variants. More importantly, single clone purification identified a significant proportion of homologous recombinants that emerged during the passage history, and immune pressure reduced the frequency of recombination. Interestingly, a recombination hot region located between nucleotide sites 22,995 and 28,866 of the viral genomes could be identified in most of the detected recombinants. Our study not only profiled the variable competitive fitness of SARS‐CoV‐2 under different conditions, but also provided direct experimental evidence of homologous recombination between SARS‐CoV‐2 viruses, as well as a model for investigating SARS‐CoV‐2 recombination.

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Transient acquisition of cross-species infectivity during the evolution of SARS-CoV-2

Cited by 20 publications

References 10 publications

Lipid nanoparticle-encapsulated mRNA antibody provides long-term protection against SARS-CoV-2 in mice and hamsters

Lipid nanoparticle-encapsulated mRNA antibody provides long-term protection against SARS-CoV-2 in mice and hamsters

Comparative characterization of SARS‐CoV‐2 variants of concern and mouse‐adapted strains in mice

Competitive fitness and homologous recombination of SARS‐CoV‐2 variants of concern

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