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
The ongoing COVID-19 pandemic and its unprecedented global societal and economic disruptive impact highlight the urgent need for safe and effective vaccines.Taking substantial advantages of versatility and rapid devel...The ongoing COVID-19 pandemic and its unprecedented global societal and economic disruptive impact highlight the urgent need for safe and effective vaccines.Taking substantial advantages of versatility and rapid development,two m RNA vaccines against COVID-19 have completed late-stage clinical assessment at an unprecedented speed and reported positive results.In this review,we outline keynotes in m RNA vaccine development,discuss recently published data on COVID-19 m RNA vaccine candidates,focusing on those in clinical trials and analyze future potential challenges.展开更多
Dear Editor,The emergence of severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)variants threatens efforts to contain the coronavirus disease 2019(COVID-19)pandemic.Omicron(B.1.1.529),the fifth novel SARS-CoV-...Dear Editor,The emergence of severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)variants threatens efforts to contain the coronavirus disease 2019(COVID-19)pandemic.Omicron(B.1.1.529),the fifth novel SARS-CoV-2 variant of concern(VOC),harbors 15 mutations in the receptor-binding domain(RBD)of the spike(S)protein.1 These mutations include almost all the sites of existing VOCs(Alpha/B.1.1.7,Beta/B.1.351,Gamma/P.1,and Delta/B.1.617.2).2–4 Importantly,the key mutations directly interact with the ACE2 receptor and constitute the main target of neutralizing antibodies(NAbs),which is believed to alter the sensitivity to a large number of NAbs.展开更多
Dear Editor,By targeting the programmed cell death 1(PD-1)pathway with monoclonal antibodies(mAbs),immune checkpoint therapy(ICT)has achieved unprecedented clinical success in the treatment of multiple tumors.1,2 Canc...Dear Editor,By targeting the programmed cell death 1(PD-1)pathway with monoclonal antibodies(mAbs),immune checkpoint therapy(ICT)has achieved unprecedented clinical success in the treatment of multiple tumors.1,2 Cancer cells evade the host immune system via both the tolerance of T cells and functional suppression of innate immune cells.3 CD47 provides a“do not eat me”signal by binding to signal regulatory protein alpha(SIRPα)to prevent innate immune cells from attacking host cells.4 Recently,macrophages were found to restore antitumor reactivity by blocking the interaction between upregulated CD47 on tumor cells and SIRPαon innate immune cells.5 However,it remains unknown whether there are blocking“hotspots”on CD47 for mAb-based anti-CD47 therapy or additional blocking hotspot regions within CD47 for therapeutic mAb development.Although it is overexpressed on tumor cells,CD47 is also expressed in many normal cells,including red blood cells and platelets.6 Some validated CD47-blocking mAbs under clinical investigation induce hemagglutination and anemia.7 Thus,designing an engineered CD47-blocking antibody to exert a therapeutic effect with limited hemagglutination is needed.展开更多
The ongoing COVID-19 pandemic,caused by SARS-CoV-2,is an imprecedented challenge to humanity.Global herd immunity may be necessary before resumption of normal economic and societal activities.Since the beginning of th...The ongoing COVID-19 pandemic,caused by SARS-CoV-2,is an imprecedented challenge to humanity.Global herd immunity may be necessary before resumption of normal economic and societal activities.Since the beginning of the outbreak,the development of COVID-19 vaccines has proceeded at record speed using nearly all available platforms or strategies to maximize vaccine success.A total of 42 vaccine candidates have now entered clinical trials and encouraging data from several vaccine candidates in phase 1 or 2 clinical trials have been reported.In this review,we examine current COVID-19 vaccine candidates,discuss their strengths and weaknesses,summarize published clinical data and analyze future challenges.展开更多
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.
基金supported by the National Key Research and Development Project(2020YFC0842300)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29040201)The National Natural Science Foundation of China(81901680)。
文摘The ongoing COVID-19 pandemic and its unprecedented global societal and economic disruptive impact highlight the urgent need for safe and effective vaccines.Taking substantial advantages of versatility and rapid development,two m RNA vaccines against COVID-19 have completed late-stage clinical assessment at an unprecedented speed and reported positive results.In this review,we outline keynotes in m RNA vaccine development,discuss recently published data on COVID-19 m RNA vaccine candidates,focusing on those in clinical trials and analyze future potential challenges.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29040201)the National Natural Science Foundation of China(NSFC)(81901680)。
基金This project was funded by the Strategic Priority Research Program of CAS(XDB29040201)the National Natural Science Foundation of China(81830050)China Postdoctoral Science Foundation(2021M703450).
文摘Dear Editor,The emergence of severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)variants threatens efforts to contain the coronavirus disease 2019(COVID-19)pandemic.Omicron(B.1.1.529),the fifth novel SARS-CoV-2 variant of concern(VOC),harbors 15 mutations in the receptor-binding domain(RBD)of the spike(S)protein.1 These mutations include almost all the sites of existing VOCs(Alpha/B.1.1.7,Beta/B.1.351,Gamma/P.1,and Delta/B.1.617.2).2–4 Importantly,the key mutations directly interact with the ACE2 receptor and constitute the main target of neutralizing antibodies(NAbs),which is believed to alter the sensitivity to a large number of NAbs.
基金supported by the China National Grand S&T Special Project(2018ZX10302302)the Strategic Priority Research Program of the Chinese Academy of Sciences(CAS)(XDA12020358)G.F.G.and J.Y.are supported by the NSFC Innovative Research Group(Grant No.81621091).
文摘Dear Editor,By targeting the programmed cell death 1(PD-1)pathway with monoclonal antibodies(mAbs),immune checkpoint therapy(ICT)has achieved unprecedented clinical success in the treatment of multiple tumors.1,2 Cancer cells evade the host immune system via both the tolerance of T cells and functional suppression of innate immune cells.3 CD47 provides a“do not eat me”signal by binding to signal regulatory protein alpha(SIRPα)to prevent innate immune cells from attacking host cells.4 Recently,macrophages were found to restore antitumor reactivity by blocking the interaction between upregulated CD47 on tumor cells and SIRPαon innate immune cells.5 However,it remains unknown whether there are blocking“hotspots”on CD47 for mAb-based anti-CD47 therapy or additional blocking hotspot regions within CD47 for therapeutic mAb development.Although it is overexpressed on tumor cells,CD47 is also expressed in many normal cells,including red blood cells and platelets.6 Some validated CD47-blocking mAbs under clinical investigation induce hemagglutination and anemia.7 Thus,designing an engineered CD47-blocking antibody to exert a therapeutic effect with limited hemagglutination is needed.
基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29040201)the National Natural Science Foundation of China(NSFC)(81901680)National Key Research and Development Project(2020YFC0842300).
文摘The ongoing COVID-19 pandemic,caused by SARS-CoV-2,is an imprecedented challenge to humanity.Global herd immunity may be necessary before resumption of normal economic and societal activities.Since the beginning of the outbreak,the development of COVID-19 vaccines has proceeded at record speed using nearly all available platforms or strategies to maximize vaccine success.A total of 42 vaccine candidates have now entered clinical trials and encouraging data from several vaccine candidates in phase 1 or 2 clinical trials have been reported.In this review,we examine current COVID-19 vaccine candidates,discuss their strengths and weaknesses,summarize published clinical data and analyze future challenges.
