The ongoing coronavirus disease 2019(COVID-19)pandemic caused more than 96 million infections and over 2 million deaths worldwide so far.However,there is no approved vaccine available for severe acute respiratory synd...The ongoing coronavirus disease 2019(COVID-19)pandemic caused more than 96 million infections and over 2 million deaths worldwide so far.However,there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the disease causative agent.Vaccine is the most effective approach to eradicate a pathogen.The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations.Here we evaluated the safety,immunogenicity,and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates.Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates,and subsequently provided partial(in low dose)or full(in high dose)protection of challenge in the tested animals.In addition,passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice.These results warranted positive outcomes in future clinical trials in humans.展开更多
Dear Editor,The ongoing COVID-19 disease,caused by severe acute respiratory syndrome coronavirus 2(SARS-Co V-2),has led to over 112 million confirmed cases and 2.4 million deaths in more than 220 countries as of 25 Fe...Dear Editor,The ongoing COVID-19 disease,caused by severe acute respiratory syndrome coronavirus 2(SARS-Co V-2),has led to over 112 million confirmed cases and 2.4 million deaths in more than 220 countries as of 25 February 2021(WHO 2021).Hospital-admitted patients show clinical features including fever,dry cough,fatigue,dyspnea,lymphopenia,and pneumonia with radiological groundglass lung opacities(Huang et al.2020;Guan et al.2020).SARS-Co V-2 was quickly isolated and could be detected in clinical samples,such as nasopharyngeal swabs,sputum,alveolar lavage fluid,and feces,as well as occasionally in seminal fluid and tears among other sources(Bhat et al.2020;Li et al.2020),which means that it can infect a variety of human tissues and organs.展开更多
SARS-CoV-2 induced marked lymphopenia in severe patients with COVID-19.However,whether lymphocytes are targets of viral infection is yet to be determined,although SARS-CoV-2 RNA or antigen has been identified in T cel...SARS-CoV-2 induced marked lymphopenia in severe patients with COVID-19.However,whether lymphocytes are targets of viral infection is yet to be determined,although SARS-CoV-2 RNA or antigen has been identified in T cells from patients.Here,we confirmed that SARS-CoV-2 viral antigen could be detected in patient peripheral blood cells(PBCs)or postmortem lung T cells,and the infectious virus could also be detected from viral antigen-positive PBCs.We next prove that SARS-CoV-2 infects T lymphocytes,preferably activated CD4+T cells in vitro.Upon infection,viral RNA,subgenomic RNA,viral protein or viral particle can be detected in the T cells.Furthermore,we show that the infection is spike-ACE2/TMPRSS2-independent through using ACE2 knockdown or receptor blocking experiments.Next,we demonstrate that viral antigen-positive T cells from patient undergone pronounced apoptosis.In vitro infection of T cells induced cell death that is likely in mitochondria ROS-HIF-1a-dependent pathways.Finally,we demonstrated that LFA-1,the protein exclusively expresses in multiple leukocytes,is more likely the entry molecule that mediated SARS-CoV-2 infection in T cells,compared to a list of other known receptors.Collectively,this work confirmed a SARS-CoV-2 infection of T cells,in a spike-ACE2-independent manner,which shed novel insights into the underlying mechanisms of SARS-CoV2-induced lymphopenia in COVID-19 patients.展开更多
基金supported by the National Key R&D Program of China(2020YFC0842000 to Z.M.Yuan and 2020YFC0842100 to C.Shan)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29010101 to Z.L.Shi)+1 种基金the China Natural Science Foundation(82041013 to P.Zhou)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(CAS)(2019328 to X.L.Yang)。
文摘The ongoing coronavirus disease 2019(COVID-19)pandemic caused more than 96 million infections and over 2 million deaths worldwide so far.However,there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the disease causative agent.Vaccine is the most effective approach to eradicate a pathogen.The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations.Here we evaluated the safety,immunogenicity,and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates.Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates,and subsequently provided partial(in low dose)or full(in high dose)protection of challenge in the tested animals.In addition,passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice.These results warranted positive outcomes in future clinical trials in humans.
基金supported by the China Natural Science Foundation(32070180 to X.-L.Y.,31770175 to Z.-L.S.)Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29010101 to Z.-L.S.)a Youth innovation promotion association of CAS(2019328 to X.-L.Y.)。
文摘Dear Editor,The ongoing COVID-19 disease,caused by severe acute respiratory syndrome coronavirus 2(SARS-Co V-2),has led to over 112 million confirmed cases and 2.4 million deaths in more than 220 countries as of 25 February 2021(WHO 2021).Hospital-admitted patients show clinical features including fever,dry cough,fatigue,dyspnea,lymphopenia,and pneumonia with radiological groundglass lung opacities(Huang et al.2020;Guan et al.2020).SARS-Co V-2 was quickly isolated and could be detected in clinical samples,such as nasopharyngeal swabs,sputum,alveolar lavage fluid,and feces,as well as occasionally in seminal fluid and tears among other sources(Bhat et al.2020;Li et al.2020),which means that it can infect a variety of human tissues and organs.
基金the Natural Science Foundation of China(excellent scholars 81822028,82041013,and 81772199 to P.Z.,and 81974456 and 82170081 to H.L.Z.)Strategic Priority Research Program of the CAS(grant number XDB29010204)to P.Z.
文摘SARS-CoV-2 induced marked lymphopenia in severe patients with COVID-19.However,whether lymphocytes are targets of viral infection is yet to be determined,although SARS-CoV-2 RNA or antigen has been identified in T cells from patients.Here,we confirmed that SARS-CoV-2 viral antigen could be detected in patient peripheral blood cells(PBCs)or postmortem lung T cells,and the infectious virus could also be detected from viral antigen-positive PBCs.We next prove that SARS-CoV-2 infects T lymphocytes,preferably activated CD4+T cells in vitro.Upon infection,viral RNA,subgenomic RNA,viral protein or viral particle can be detected in the T cells.Furthermore,we show that the infection is spike-ACE2/TMPRSS2-independent through using ACE2 knockdown or receptor blocking experiments.Next,we demonstrate that viral antigen-positive T cells from patient undergone pronounced apoptosis.In vitro infection of T cells induced cell death that is likely in mitochondria ROS-HIF-1a-dependent pathways.Finally,we demonstrated that LFA-1,the protein exclusively expresses in multiple leukocytes,is more likely the entry molecule that mediated SARS-CoV-2 infection in T cells,compared to a list of other known receptors.Collectively,this work confirmed a SARS-CoV-2 infection of T cells,in a spike-ACE2-independent manner,which shed novel insights into the underlying mechanisms of SARS-CoV2-induced lymphopenia in COVID-19 patients.
