BA.2 is a novel omicron offshoot of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)that has gone viral.There is limited knowledge regarding this variant of concern.Current evidence suggests that this varia...BA.2 is a novel omicron offshoot of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)that has gone viral.There is limited knowledge regarding this variant of concern.Current evidence suggests that this variant is more contagious but less severe than previous SARS-CoV-2 variants.However,there is concern regarding the virus mutations that could influence pathogenicity,transmissibility,and immune evasion.展开更多
Since the outbreak of COVID-19,severe acute respiratory syndrome coronavirus 2 genome is still mutating,forming a variety of variants with strong transmission capacity,causing the spread of the epidemic worldwide,posi...Since the outbreak of COVID-19,severe acute respiratory syndrome coronavirus 2 genome is still mutating,forming a variety of variants with strong transmission capacity,causing the spread of the epidemic worldwide,posing a serious threat to people's physical and mental health,and posing a major challenge to global public health.Omicron remains the main variant in several outbreaks worldwide,accounting for about 99%of the global genetic sequence.Recently,the World Health Organization announced that the subvariant of Omicron BA.5 has been found in more than 100 countries and regions around the world,causing the global epidemic rebound.However,there are few studies on the subvariant BA.5.This article reviews the latest research progress in epidemiology,infectivity,pathogenicity,vaccine and monoclonal antibody protection against Omicron subvariant BA.5,in order to provide reference for scientific prevention and control of Omicron subvariant BA.5.展开更多
Large population passages of the SARS-CoV-2 in the past two and a half years have allowed the circulating virus to accumulate an increasing number of mutations in its genome. The most recently emerging Omicron subvari...Large population passages of the SARS-CoV-2 in the past two and a half years have allowed the circulating virus to accumulate an increasing number of mutations in its genome. The most recently emerging Omicron subvariants have the highest number of mutations in the Spike (S) protein gene and these mutations mainly occur in the receptor-binding domain (RBD) and the N-terminal domain (NTD) of the S gene. The European Centre for Disease Prevention and Control (eCDC) and the World Health Organization (WHO) recommend partial Sanger sequencing of the SARS-CoV-2 S gene RBD and NTD on the polymerase chain reaction (PCR)-positive samples in diagnostic laboratories as a practical means of determining the variants of concern to monitor possible increased transmissibility, increased virulence, or reduced effectiveness of vaccines against them. The author’s diagnostic laboratory has implemented the eCDC/WHO recommendation by sequencing a 398-base segment of the N gene for the definitive detection of SARS-CoV-2 in clinical samples, and sequencing a 445-base segment of the RBD and a 490 - 509-base segment of the NTD for variant determination. This paper presents 5 selective cases to illustrate the challenges of using Sanger sequencing to diagnose Omicron subvariants when the samples harbor a high level of co-existing minor subvariant sequences with multi-allelic single nucleotide polymorphisms (SNPs) or possible recombinant Omicron subvariants containing a BA.2 RBD and an atypical BA.1 NTD, which can only be detected by using specially designed PCR primers. In addition, Sanger sequencing may reveal unclassified subvariants, such as BA.4/BA.5 with L84I mutation in the S gene NTD. The current large-scale surveillance programs using next-generation sequencing (NGS) do not face similar problems because NGS focuses on deriving consensus sequence.展开更多
With continuous mutations of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the severe immune escape of Omicron sub-variants urges the development of next-generation broad-spectrum vaccines,especially as ...With continuous mutations of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the severe immune escape of Omicron sub-variants urges the development of next-generation broad-spectrum vaccines,especially as booster jabs after high-level vaccination coverage of inactivated vaccines in China and many other countries.Previously,we developed a coronavirus disease 2019(COVID-19)protein subunit vaccine ZF2001?based on the tandem homo-prototype receptor-binding domain(RBD)-dimer of the SARS-CoV-2 spike protein.We upgraded the antigen into a hetero-chimeric prototype(PT)-Beta or Delta-BA.1 RBD-dimer to broaden the cross-protection efficacy and prove its efficiency with protein subunit and mRNA vaccine platforms.Herein,we further explored the hetero-chimeric RBD-dimer mRNA vaccines and evaluated their broad-spectrum activities as booster jabs following two doses of inactivated vaccine(Ⅳ)in mice.Our data demonstrated that the chi-meric vaccines significantly boosted neutralizing antibody levels and specific T-cell responses against the vari-ants,and PT-Beta was superior to Delta-BA.1 RBD as a booster in mice,shedding light on the antigen design for the next-generation COVID-19 vaccines.展开更多
文摘BA.2 is a novel omicron offshoot of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)that has gone viral.There is limited knowledge regarding this variant of concern.Current evidence suggests that this variant is more contagious but less severe than previous SARS-CoV-2 variants.However,there is concern regarding the virus mutations that could influence pathogenicity,transmissibility,and immune evasion.
基金COVID-19 Emergency Medical Research Project of 940 Hospital(No.20yjky020)General Project of Huoshenshan Hospital Scientific Research Fund(No.HSS-217)。
文摘Since the outbreak of COVID-19,severe acute respiratory syndrome coronavirus 2 genome is still mutating,forming a variety of variants with strong transmission capacity,causing the spread of the epidemic worldwide,posing a serious threat to people's physical and mental health,and posing a major challenge to global public health.Omicron remains the main variant in several outbreaks worldwide,accounting for about 99%of the global genetic sequence.Recently,the World Health Organization announced that the subvariant of Omicron BA.5 has been found in more than 100 countries and regions around the world,causing the global epidemic rebound.However,there are few studies on the subvariant BA.5.This article reviews the latest research progress in epidemiology,infectivity,pathogenicity,vaccine and monoclonal antibody protection against Omicron subvariant BA.5,in order to provide reference for scientific prevention and control of Omicron subvariant BA.5.
文摘Large population passages of the SARS-CoV-2 in the past two and a half years have allowed the circulating virus to accumulate an increasing number of mutations in its genome. The most recently emerging Omicron subvariants have the highest number of mutations in the Spike (S) protein gene and these mutations mainly occur in the receptor-binding domain (RBD) and the N-terminal domain (NTD) of the S gene. The European Centre for Disease Prevention and Control (eCDC) and the World Health Organization (WHO) recommend partial Sanger sequencing of the SARS-CoV-2 S gene RBD and NTD on the polymerase chain reaction (PCR)-positive samples in diagnostic laboratories as a practical means of determining the variants of concern to monitor possible increased transmissibility, increased virulence, or reduced effectiveness of vaccines against them. The author’s diagnostic laboratory has implemented the eCDC/WHO recommendation by sequencing a 398-base segment of the N gene for the definitive detection of SARS-CoV-2 in clinical samples, and sequencing a 445-base segment of the RBD and a 490 - 509-base segment of the NTD for variant determination. This paper presents 5 selective cases to illustrate the challenges of using Sanger sequencing to diagnose Omicron subvariants when the samples harbor a high level of co-existing minor subvariant sequences with multi-allelic single nucleotide polymorphisms (SNPs) or possible recombinant Omicron subvariants containing a BA.2 RBD and an atypical BA.1 NTD, which can only be detected by using specially designed PCR primers. In addition, Sanger sequencing may reveal unclassified subvariants, such as BA.4/BA.5 with L84I mutation in the S gene NTD. The current large-scale surveillance programs using next-generation sequencing (NGS) do not face similar problems because NGS focuses on deriving consensus sequence.
基金This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(grant number XDB29040203)the National Key Research and Development Program of China(grant number 2021YFA1301404 and 2020YFA0907102)+2 种基金the National Natural Science Foundation of China(grant numbers 82225021 and 32171428)In addition,Qihui Wang was supported by the CAS Project for Young Scientists in Basic Research(grant number YSBR-010)the Youth Innovation Promotion Association of the CAS(grant number Y2022037).We thank Professor Xiao Zhao from the National Center for Nanoscience and Technology for sharing the LNP encapsulation and DLS platforms.We thank Dr.Kun Xu for his help during the revision of this manuscript.We thank Linjie Li for sharing recombinant RBD proteins.We thank the Institutional Center for Shared Technology and Facilitates in the Institute of Microbiology,CAS,and the Institute of Zoology,CAS.
文摘With continuous mutations of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the severe immune escape of Omicron sub-variants urges the development of next-generation broad-spectrum vaccines,especially as booster jabs after high-level vaccination coverage of inactivated vaccines in China and many other countries.Previously,we developed a coronavirus disease 2019(COVID-19)protein subunit vaccine ZF2001?based on the tandem homo-prototype receptor-binding domain(RBD)-dimer of the SARS-CoV-2 spike protein.We upgraded the antigen into a hetero-chimeric prototype(PT)-Beta or Delta-BA.1 RBD-dimer to broaden the cross-protection efficacy and prove its efficiency with protein subunit and mRNA vaccine platforms.Herein,we further explored the hetero-chimeric RBD-dimer mRNA vaccines and evaluated their broad-spectrum activities as booster jabs following two doses of inactivated vaccine(Ⅳ)in mice.Our data demonstrated that the chi-meric vaccines significantly boosted neutralizing antibody levels and specific T-cell responses against the vari-ants,and PT-Beta was superior to Delta-BA.1 RBD as a booster in mice,shedding light on the antigen design for the next-generation COVID-19 vaccines.
