Dear Editor,The pandemic of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),continues despite extensive efforts to control viral transmission.Meanwhile,the emerg...Dear Editor,The pandemic of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),continues despite extensive efforts to control viral transmission.Meanwhile,the emergence of SARS-CoV-2 variants with antigenically divergence in viral protein dampens the efficacy of authorized vaccines,leading to the breakthrough infections in vaccinated population(Cao et al.,2021,2022;Tuekprakhon et al.,2022;Xiang et al.,2022).Moreover,diverse sarbecoviruses in bats and pangolins have been discovered and isolated(Ge et al.,2013;Xiao et al.,2020).Some of these viruses have exhibited efficient binding to human angiotensin-converting enzyme 2(hACE2)(Xiao et al.,2020;Liu et al.,2021;Temmam et al.,2022),highlighting the risk of spillover from wild animals to human.Thus,the development of pan-sarbecovirus vaccines is of high priority.展开更多
Objective:This study aimed to explore undergraduates’knowledge,attitude,and practice/behavior of human papillomavirus(HPV)vaccination,as well as the essential influencing factors for vaccination decision-making.Metho...Objective:This study aimed to explore undergraduates’knowledge,attitude,and practice/behavior of human papillomavirus(HPV)vaccination,as well as the essential influencing factors for vaccination decision-making.Methods:Through cluster and convenience sampling,2000 undergraduates from the Nursing and Language department of a university in Shanghai were sent a self-designed questionnaire.Chi-square tests,independent sample t-test/ANOVE,and multiple linear regression were used to investigate participants’knowledge and attitude on HPV vaccination,as well as the factors that predicted potential action to receive and promote HPV vaccination in the future.Results:The mean HPV knowledge score was 5.027 out of 10.Health science students showed a significantly higher knowledge mean score than the non-health science students(P<0.000).There was a statistically difference in HPV vaccination attitude among undergraduates in different grades(P<0.05).Awareness of cervical cancer and worries about the risk of cervical cancer were the significant predictors of willingness to receive and promote HPV vaccination in the future.Conclusions:It would take time for a new health product to be aware,understood,accepted,and received.Education providing and information sharing are expected to break the dawn and make the procedure processed.展开更多
One new stenine-type alkaloid, tuberostemonine D （1）, together with five known stenine-type alkaloids （2-6） and two known stemoninine-type alkaloids （7 and 8）, were isolated from the roots of Stemona tuberosa. T...One new stenine-type alkaloid, tuberostemonine D （1）, together with five known stenine-type alkaloids （2-6） and two known stemoninine-type alkaloids （7 and 8）, were isolated from the roots of Stemona tuberosa. Their structures were elucidated by extensive spectroscopic methods （IR, UV, MS, 1D and 2D NMR）, and the structure of I was further confirmed by X-ray diffraction analysis. First simultaneous isolation ofstenine- and stemoninine-type alkaloids not only added a new chemical type and increased the chemical diversity of Stemona tuberosa, but also provided chemotaxonomic clues for the close relationship between genera Stemona and Stichoneuron, and favored retaining them in the same family.展开更多
Carrot(Daucus carota)is an Apiaceae plant with multi-colored fleshy roots that provides a model system for carotenoid research.In this study,we assembled a 430.40 Mb high-quality gapless genome to the telomere-to-telo...Carrot(Daucus carota)is an Apiaceae plant with multi-colored fleshy roots that provides a model system for carotenoid research.In this study,we assembled a 430.40 Mb high-quality gapless genome to the telomere-to-telomere(T2T)level of“Kurodagosun”carrot.In total,36268 genes were identified and 34961 of them were functionally annotated.The proportion of repeat sequences in the genome was 55.3%,mainly long terminal repeats.Depending on the coverage of the repeats,14 telomeres and 9 centromeric regions on the chromosomes were predicted.A phylogenetic analysis showed that carrots evolved early in the family Apiaceae.Based on the T2T genome,we reconstructed the carotenoid metabolic pathway and identified the structural genes that regulate carotenoid biosynthesis.Among the 65 genes that were screened,9 were newly identified.Additionally,some gene sequences overlapped with transposons,suggesting replication and functional differentiation of carotenoid-related genes during carrot evolution.Given that some gene copies were barely expressed during development,they might be functionally redundant.Comparison of 24 cytochrome P450 genes associated with carotenoid biosynthesis revealed the tandem or proximal duplication resulting in expansion of CYP gene family.These results provided molecular information for carrot carotenoid accumulation and contributed to a new genetic resource.展开更多
Dear Editor,Since the outbreak of COVID-19 at the end of 2019,its causative agent SARS-Co V-2 has been spreading around the world for one and half a year.During the long global circulation of SARS-Co V-2,mutations in ...Dear Editor,Since the outbreak of COVID-19 at the end of 2019,its causative agent SARS-Co V-2 has been spreading around the world for one and half a year.During the long global circulation of SARS-Co V-2,mutations in the viral genome gradually emerged and accumulated。展开更多
DEAR EDITOR,Bostrychus,a genus in the family Eleotridae of the order Gobiiformes,was first established by Lacepède in 1801(Buffon,1801).Bostrychus currently contains seven recognized species,including two recent ...DEAR EDITOR,Bostrychus,a genus in the family Eleotridae of the order Gobiiformes,was first established by Lacepède in 1801(Buffon,1801).Bostrychus currently contains seven recognized species,including two recent additions(B.microphthalmos and B.scalaris)described in 2005(Hoese&Kottelat,2005)and 2008(Larson,2008),respectively.The natural range of Bostrychus species extends from East Asia to Australia,with the exception of B.africanus,Steindachner,1879,which is distributed in West Africa(Herre,1946).Among the recognized species,B.sinensis,B.zonatus,and B.africanus are relatively widespread,inhabiting diverse areas from estuaries to freshwater streams,while B.scalaris is only found at a single mangrove site in the Selangor State of Malaysia(Larson,2008).The remaining three species exhibit a high degree of habitat specialization and are highly localized(Hoese&Kottelat,2005):B.microphthalmos inhabits a cave stream in the Maros karst of southern Sulawesi,B.aruensis is confined to freshwater environments in the Aru Islands of Indonesia,and B.strigogenys is found only in freshwater areas in southern Papua New Guinea and Irian Jaya.展开更多
Human Enterovirus 71(EV71)has emerged as one of the predominant causative agents of hand,foot and mouth disease(HFMD)with global impact.Despite the inactivated vaccine being licensed,other vaccine candidates based on ...Human Enterovirus 71(EV71)has emerged as one of the predominant causative agents of hand,foot and mouth disease(HFMD)with global impact.Despite the inactivated vaccine being licensed,other vaccine candidates based on advanced technology platforms are under development.In this report,we rationally designed and constructed two DNA-launched live attenuated vaccine candidates(pDL-EV71)under the control of specific promoters.In vitro and in vivo transfection with pDL-EV71 driven by the CMV promoter successfully yielded fully infectious EV71.More importantly,the administration of pDL-EV71 did not cause clinical symptoms following intracranial or intramuscular inoculation in neonatal and IFNα/βR/mice,demonstrating its safety profile.Moreover,a single-dose or two-dose immunization with pDL-EV71 elicited robust neutralizing antibodies against EV71 as well as an antigen-specific cellular response in mice.A single-dose immunization with 10μg of pDL-EV71 conferred complete protection against lethal EV71 infection in neonates born to immunized maternal mice.Overall,our present results demonstrate that pDL-EV71 is a safe and effective vaccine candidate against EV71 for further development.展开更多
DEAR EDITOR,The Pegasidae family,which includes seven species of seamoths,is widely distributed in the temperate and tropical waters of the Indo-Pacific,ranging from South Africa to Hawaii.In this study,we describe a ...DEAR EDITOR,The Pegasidae family,which includes seven species of seamoths,is widely distributed in the temperate and tropical waters of the Indo-Pacific,ranging from South Africa to Hawaii.In this study,we describe a new species of seamoth,Pegasus sinensis sp.nov.,based on morphological and molecular characterization of 14 specimens collected from the surrounding waters of Xiamen City,Fujian Province,China.The new species differs from closely related P.volitans in both the density and color of spots present on the dorsal and lateral body surfaces.展开更多
Betalains are tyrosine-derived plant pigments exclusively found in the Caryophyllales order and some higher fungi and generally classified into two groups:red-violet betacyanins and yellow-orange betaxanthins.Betalain...Betalains are tyrosine-derived plant pigments exclusively found in the Caryophyllales order and some higher fungi and generally classified into two groups:red-violet betacyanins and yellow-orange betaxanthins.Betalains attract great scientific and economic interest because of their relatively simple biosynthesis pathway,attractive colors and health-promoting properties.Co-expressing two core genes BvCYP76AD1 and BvDODA1 with or without a glycosyltransferase gene MjcDOPA5GT allowed the engineering of carrot(an important taproot vegetable)to produce a palette of unique colors.The highest total betalains content,943.2μg·g^(−1) DW,was obtained in carrot taproot transformed with p35S:RUBY which produces all of the necessary enzymes for betalains synthesis.Root-specific production of betalains slightly relieved tyrosine consumption revealing the possible bottleneck in betalains production.Furthermore,a unique volcano-like phenotype in carrot taproot cross-section was created by vascular cambium-specific production of betalains.The betalains-fortified carrot in this study is thus anticipated to be used as functional vegetable and colorful carrot germplasm in breeding to promote health.展开更多
Objective:To explore the effect of peer education on improving the knowledge,attitude,practice level(KAP)to prevent human papilloma virus(HPV)infection among college students.Methods:The knowledge,attitude/belief,and ...Objective:To explore the effect of peer education on improving the knowledge,attitude,practice level(KAP)to prevent human papilloma virus(HPV)infection among college students.Methods:The knowledge,attitude/belief,and practice level of 536 grade I college students from a university in Shanghai were surveyed and analyzed using a self-designed questionnaire—the HPV Infection and Prevention KAP Questionnaire.Results:Many college students heard about HPV vaccine(49.70%before peer education and 100%after peer education);however,few of them were vaccinated(2.82%before peer education and 5.23%after peer education).Knowledge,attitude/belied,and practice of HPV infection prevention were positively related(P<0.05).Peer education was effective in improving college students'KAP level of HPV infection prevention(P<0.05).Conclusions:Peer education could be used as a strategy in colleges to improve student's KAP level of HPV infection prevention.College students may also be encouraged to spread their influence to society.展开更多
Dear Editor,Genetic code expansion based on orthogonal tRNA-aminoacyl tRNA synthetase is an emerging technology to sitespecifically incorporate unnatural amino acids(UAAs)into viral proteins to produce UAA-controlled ...Dear Editor,Genetic code expansion based on orthogonal tRNA-aminoacyl tRNA synthetase is an emerging technology to sitespecifically incorporate unnatural amino acids(UAAs)into viral proteins to produce UAA-controlled replication-defective virus.展开更多
The Orthopoxvirus genus,especially variola virus(VARV),monkeypox virus(MPXV),remains a significant public health threat worldwide.The development of therapeutic antibodies against orthopoxviruses is largely hampered b...The Orthopoxvirus genus,especially variola virus(VARV),monkeypox virus(MPXV),remains a significant public health threat worldwide.The development of therapeutic antibodies against orthopoxviruses is largely hampered by the high cost of antibody engineering and manufacturing processes.mRNA-encoded antibodies have emerged as a powerful and universal platform for rapid antibody production.Herein,by using the established lipid nanoparticle(LNP)-encapsulated mRNA platform,we constructed four mRNA combinations that encode monoclonal antibodies with broad neutralization activities against orthopoxviruses.In vivo characterization demonstrated that a single intravenous injection of each LNP-encapsulated mRNA antibody in mice resulted in the rapid production of neutralizing antibodies.More importantly,mRNA antibody treatments showed significant protection from weight loss and mortality in the vaccinia virus(VACV)lethal challenge mouse model,and a unique mRNA antibody cocktail,Mix2a,exhibited superior in vivo protection by targeting both intracellular mature virus(IMV)-form and extracellular enveloped virus(EEV)-form viruses.In summary,our results demonstrate the proof-of-concept production of orthopoxvirus antibodies via the LNP-mRNA platform,highlighting the great potential of tailored mRNA antibody combinations as a universal strategy to combat orthopoxvirus as well as otheremerging viruses.展开更多
The highly pathogenic and readily transmissible SARS-CoV-2 has caused a global coronavirus pandemic,urgently requiring effective countermeasures against its rapid expansion.All available vaccine platforms are being us...The highly pathogenic and readily transmissible SARS-CoV-2 has caused a global coronavirus pandemic,urgently requiring effective countermeasures against its rapid expansion.All available vaccine platforms are being used to generate safe and effective COVID-19 vaccines.Here,we generated a live-attenuated candidate vaccine strain by serial passaging of a SARSCoV-2 clinical isolate in Vero cells.展开更多
基金supported by the National Key Research and Development Program of China(2021YFC2302400)the National Natural Science Foundation of China(82241069 and 82350801)+2 种基金supported by the National Science Fund for Distinguished Young Scholar(81925025)the Innovation Fund for Medical Sciences(2019-I2M-5-049)from the Chinese Academy of Medical Sciencessponsored by Beijing Nova Program(20240484525).
文摘Dear Editor,The pandemic of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),continues despite extensive efforts to control viral transmission.Meanwhile,the emergence of SARS-CoV-2 variants with antigenically divergence in viral protein dampens the efficacy of authorized vaccines,leading to the breakthrough infections in vaccinated population(Cao et al.,2021,2022;Tuekprakhon et al.,2022;Xiang et al.,2022).Moreover,diverse sarbecoviruses in bats and pangolins have been discovered and isolated(Ge et al.,2013;Xiao et al.,2020).Some of these viruses have exhibited efficient binding to human angiotensin-converting enzyme 2(hACE2)(Xiao et al.,2020;Liu et al.,2021;Temmam et al.,2022),highlighting the risk of spillover from wild animals to human.Thus,the development of pan-sarbecovirus vaccines is of high priority.
文摘Objective:This study aimed to explore undergraduates’knowledge,attitude,and practice/behavior of human papillomavirus(HPV)vaccination,as well as the essential influencing factors for vaccination decision-making.Methods:Through cluster and convenience sampling,2000 undergraduates from the Nursing and Language department of a university in Shanghai were sent a self-designed questionnaire.Chi-square tests,independent sample t-test/ANOVE,and multiple linear regression were used to investigate participants’knowledge and attitude on HPV vaccination,as well as the factors that predicted potential action to receive and promote HPV vaccination in the future.Results:The mean HPV knowledge score was 5.027 out of 10.Health science students showed a significantly higher knowledge mean score than the non-health science students(P<0.000).There was a statistically difference in HPV vaccination attitude among undergraduates in different grades(P<0.05).Awareness of cervical cancer and worries about the risk of cervical cancer were the significant predictors of willingness to receive and promote HPV vaccination in the future.Conclusions:It would take time for a new health product to be aware,understood,accepted,and received.Education providing and information sharing are expected to break the dawn and make the procedure processed.
基金supported by the Fundamental Research Funds for the Central Universities (No.11612603)the Science and Technology Planning Project of Zhongshan City (No.2013A3FC0325)
文摘One new stenine-type alkaloid, tuberostemonine D （1）, together with five known stenine-type alkaloids （2-6） and two known stemoninine-type alkaloids （7 and 8）, were isolated from the roots of Stemona tuberosa. Their structures were elucidated by extensive spectroscopic methods （IR, UV, MS, 1D and 2D NMR）, and the structure of I was further confirmed by X-ray diffraction analysis. First simultaneous isolation ofstenine- and stemoninine-type alkaloids not only added a new chemical type and increased the chemical diversity of Stemona tuberosa, but also provided chemotaxonomic clues for the close relationship between genera Stemona and Stichoneuron, and favored retaining them in the same family.
基金This article was supported by National Natural Science Foundation of China(32072563,32102369)Natural Science Foundation of Jiangsu Province(BK20211366)+2 种基金Project of Guizhou Provincial Department of Science and Technology(Qiankehe Fuqi[2022005])Project of Guiyang of Science and Technology Bureau(Zhuke contract[2021]5-1)Priority Academic Program Development of Jiangsu Higher Education Institutions Project(PAPD).
文摘Carrot(Daucus carota)is an Apiaceae plant with multi-colored fleshy roots that provides a model system for carotenoid research.In this study,we assembled a 430.40 Mb high-quality gapless genome to the telomere-to-telomere(T2T)level of“Kurodagosun”carrot.In total,36268 genes were identified and 34961 of them were functionally annotated.The proportion of repeat sequences in the genome was 55.3%,mainly long terminal repeats.Depending on the coverage of the repeats,14 telomeres and 9 centromeric regions on the chromosomes were predicted.A phylogenetic analysis showed that carrots evolved early in the family Apiaceae.Based on the T2T genome,we reconstructed the carotenoid metabolic pathway and identified the structural genes that regulate carotenoid biosynthesis.Among the 65 genes that were screened,9 were newly identified.Additionally,some gene sequences overlapped with transposons,suggesting replication and functional differentiation of carotenoid-related genes during carrot evolution.Given that some gene copies were barely expressed during development,they might be functionally redundant.Comparison of 24 cytochrome P450 genes associated with carotenoid biosynthesis revealed the tandem or proximal duplication resulting in expansion of CYP gene family.These results provided molecular information for carrot carotenoid accumulation and contributed to a new genetic resource.
基金supported by the National Key Research and Development Project of China(2020YFC0842200,2020YFA0707801,and 2021YFC0863300)the National Natural Science Foundation of China(No.82041044)+2 种基金supported by the National Science Fund for Distinguished Young Scholars(81925025)the Innovative Research Group(81621005)from the NSFCthe Innovation Fund for Medical Sciences(2019-I2M-5-049)from the Chinese Academy of Medical Sciences。
文摘Dear Editor,Since the outbreak of COVID-19 at the end of 2019,its causative agent SARS-Co V-2 has been spreading around the world for one and half a year.During the long global circulation of SARS-Co V-2,mutations in the viral genome gradually emerged and accumulated。
基金supported by the National Natural Science Foundation of China(41776143)。
文摘DEAR EDITOR,Bostrychus,a genus in the family Eleotridae of the order Gobiiformes,was first established by Lacepède in 1801(Buffon,1801).Bostrychus currently contains seven recognized species,including two recent additions(B.microphthalmos and B.scalaris)described in 2005(Hoese&Kottelat,2005)and 2008(Larson,2008),respectively.The natural range of Bostrychus species extends from East Asia to Australia,with the exception of B.africanus,Steindachner,1879,which is distributed in West Africa(Herre,1946).Among the recognized species,B.sinensis,B.zonatus,and B.africanus are relatively widespread,inhabiting diverse areas from estuaries to freshwater streams,while B.scalaris is only found at a single mangrove site in the Selangor State of Malaysia(Larson,2008).The remaining three species exhibit a high degree of habitat specialization and are highly localized(Hoese&Kottelat,2005):B.microphthalmos inhabits a cave stream in the Maros karst of southern Sulawesi,B.aruensis is confined to freshwater environments in the Aru Islands of Indonesia,and B.strigogenys is found only in freshwater areas in southern Papua New Guinea and Irian Jaya.
基金supported by the National Key Research and Development Program of China(2021YFC2302503)the National Natural Science Foundation of China(82241069)+1 种基金Cheng-Feng Qin was supported by the National Science Fund for Distinguished Young Scholars(81925025)the Innovative Research Group from the NSFC(81621005).
文摘Human Enterovirus 71(EV71)has emerged as one of the predominant causative agents of hand,foot and mouth disease(HFMD)with global impact.Despite the inactivated vaccine being licensed,other vaccine candidates based on advanced technology platforms are under development.In this report,we rationally designed and constructed two DNA-launched live attenuated vaccine candidates(pDL-EV71)under the control of specific promoters.In vitro and in vivo transfection with pDL-EV71 driven by the CMV promoter successfully yielded fully infectious EV71.More importantly,the administration of pDL-EV71 did not cause clinical symptoms following intracranial or intramuscular inoculation in neonatal and IFNα/βR/mice,demonstrating its safety profile.Moreover,a single-dose or two-dose immunization with pDL-EV71 elicited robust neutralizing antibodies against EV71 as well as an antigen-specific cellular response in mice.A single-dose immunization with 10μg of pDL-EV71 conferred complete protection against lethal EV71 infection in neonates born to immunized maternal mice.Overall,our present results demonstrate that pDL-EV71 is a safe and effective vaccine candidate against EV71 for further development.
基金supported by the Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou)(GML2019ZD0401,GML2019ZD0407)Guangdong Basic and Applied Basic Research Foundation(2019A1515110199)+1 种基金National Natural Science Foundation of China(42006109,41825013)Key Research Program of Frontier Sciences of CAS(ZDBS-LY-DQC004)。
文摘DEAR EDITOR,The Pegasidae family,which includes seven species of seamoths,is widely distributed in the temperate and tropical waters of the Indo-Pacific,ranging from South Africa to Hawaii.In this study,we describe a new species of seamoth,Pegasus sinensis sp.nov.,based on morphological and molecular characterization of 14 specimens collected from the surrounding waters of Xiamen City,Fujian Province,China.The new species differs from closely related P.volitans in both the density and color of spots present on the dorsal and lateral body surfaces.
基金supported by the National Natural Science Foundation of China(32072563)Key Research and Development Projects of Ningxia Hui Autonomous Region(No.2022BBF02008)Priority Academic Program Development of Jiangsu Higher Education Institutions(Grant No.PAPD)。
文摘Betalains are tyrosine-derived plant pigments exclusively found in the Caryophyllales order and some higher fungi and generally classified into two groups:red-violet betacyanins and yellow-orange betaxanthins.Betalains attract great scientific and economic interest because of their relatively simple biosynthesis pathway,attractive colors and health-promoting properties.Co-expressing two core genes BvCYP76AD1 and BvDODA1 with or without a glycosyltransferase gene MjcDOPA5GT allowed the engineering of carrot(an important taproot vegetable)to produce a palette of unique colors.The highest total betalains content,943.2μg·g^(−1) DW,was obtained in carrot taproot transformed with p35S:RUBY which produces all of the necessary enzymes for betalains synthesis.Root-specific production of betalains slightly relieved tyrosine consumption revealing the possible bottleneck in betalains production.Furthermore,a unique volcano-like phenotype in carrot taproot cross-section was created by vascular cambium-specific production of betalains.The betalains-fortified carrot in this study is thus anticipated to be used as functional vegetable and colorful carrot germplasm in breeding to promote health.
文摘Objective:To explore the effect of peer education on improving the knowledge,attitude,practice level(KAP)to prevent human papilloma virus(HPV)infection among college students.Methods:The knowledge,attitude/belief,and practice level of 536 grade I college students from a university in Shanghai were surveyed and analyzed using a self-designed questionnaire—the HPV Infection and Prevention KAP Questionnaire.Results:Many college students heard about HPV vaccine(49.70%before peer education and 100%after peer education);however,few of them were vaccinated(2.82%before peer education and 5.23%after peer education).Knowledge,attitude/belied,and practice of HPV infection prevention were positively related(P<0.05).Peer education was effective in improving college students'KAP level of HPV infection prevention(P<0.05).Conclusions:Peer education could be used as a strategy in colleges to improve student's KAP level of HPV infection prevention.College students may also be encouraged to spread their influence to society.
基金supported by the National Natural Science Foundation of China(81701996)the National Key Research and Development Project of China(2018YFA0900801)。
文摘Dear Editor,Genetic code expansion based on orthogonal tRNA-aminoacyl tRNA synthetase is an emerging technology to sitespecifically incorporate unnatural amino acids(UAAs)into viral proteins to produce UAA-controlled replication-defective virus.
基金supported by the National Natural Science Foundation of China (No.82241069,and 82350801)to C.F.Q.the National Key Research and Development Project of China (2021YFC2302400)to C.F.Q.+2 种基金the Key-Area Research and Development Program of Guangdong Province (2022B1111020002).C.F.Q.supported by the National Science Fund for Distinguished Young Scholars (81925025)the Innovation Fund for Medical Sciences (2019-12M-5-049)from the Chinese Academy of Medical Sciences.
文摘The Orthopoxvirus genus,especially variola virus(VARV),monkeypox virus(MPXV),remains a significant public health threat worldwide.The development of therapeutic antibodies against orthopoxviruses is largely hampered by the high cost of antibody engineering and manufacturing processes.mRNA-encoded antibodies have emerged as a powerful and universal platform for rapid antibody production.Herein,by using the established lipid nanoparticle(LNP)-encapsulated mRNA platform,we constructed four mRNA combinations that encode monoclonal antibodies with broad neutralization activities against orthopoxviruses.In vivo characterization demonstrated that a single intravenous injection of each LNP-encapsulated mRNA antibody in mice resulted in the rapid production of neutralizing antibodies.More importantly,mRNA antibody treatments showed significant protection from weight loss and mortality in the vaccinia virus(VACV)lethal challenge mouse model,and a unique mRNA antibody cocktail,Mix2a,exhibited superior in vivo protection by targeting both intracellular mature virus(IMV)-form and extracellular enveloped virus(EEV)-form viruses.In summary,our results demonstrate the proof-of-concept production of orthopoxvirus antibodies via the LNP-mRNA platform,highlighting the great potential of tailored mRNA antibody combinations as a universal strategy to combat orthopoxvirus as well as otheremerging viruses.
基金This work was supported by the National Key Research and Development Program of China(No.2020YFC0840900,2018YFA0900801 and 2020YFA0707500)the Strategic Priority Research Program(XDB29010000,XDB37030000),CAS(YSBR-010)+5 种基金the Emergency Key Programof Guangzhou Laboratory(No.EKPG21-09)the Beijing Municipal Science and Technology Project(No.Z201100001020004,Z201100005420017)the National Natural Science Foundation of China(No.82171820,No.12034006,and No.81921005)C.-F.Q.was supported by the National Science Fund for Distinguished Young Scholars(81925025)the Innovative Research Group(81621005)from the NSFCthe Innovation Fund forMedical Sciences(2019-I2 M-5-049)from the Chinese Academy of Medical Sciences.
文摘The highly pathogenic and readily transmissible SARS-CoV-2 has caused a global coronavirus pandemic,urgently requiring effective countermeasures against its rapid expansion.All available vaccine platforms are being used to generate safe and effective COVID-19 vaccines.Here,we generated a live-attenuated candidate vaccine strain by serial passaging of a SARSCoV-2 clinical isolate in Vero cells.
