Multivalent vaccines combining crucial mutations from phylogenetically divergent variants could be an effective approach to defend against existing and future SARS-Co V-2 variants.In this study,we developed a tetraval...Multivalent vaccines combining crucial mutations from phylogenetically divergent variants could be an effective approach to defend against existing and future SARS-Co V-2 variants.In this study,we developed a tetravalent COVID-19 vaccine SCTV01E,based on the trimeric Spike protein of SARS-Co V-2 variants Alpha,Beta,Delta,and Omicron BA.1,with a squalenebased oil-in-water adjuvant SCT-VA02B.In the immunogenicity studies in na?ve BALB/c and C57BL/6J mice,SCTV01E exhibited the most favorable immunogenic characteristics to induce balanced and broad-spectrum neutralizing potencies against pre-Omicron variants(D614G,Alpha,Beta,and Delta)and newly emerging Omicron subvariants(BA.1,BA.1.1,BA.2,BA.3,and BA.4/5).Booster studies in C57BL/6J mice previously immunized with D614G monovalent vaccine demonstrated superior neutralizing capacities of SCTV01E against Omicron subvariants,compared with the D614G booster regimen.Furthermore,SCTV01E vaccination elicited na?ve and central memory T cell responses to SARS-Co V-2 ancestral strain and Omicron spike peptides.Together,our comprehensive immunogenicity evaluation results indicate that SCTV01E could become an important COVID-19 vaccine platform to combat surging infections caused by the highly immune evasive BA.4/5 variants.SCTV01E is currently being studied in a head-to-head immunogenicity comparison phase 3 clinical study with inactivated and m RNA vaccines(NCT05323461).展开更多
The Omicron variants spread rapidly worldwide after being initially detected in South Africa in November 2021.It showed increased transmissibility and immune evasion with far more amino acid mutations in the spike(S)p...The Omicron variants spread rapidly worldwide after being initially detected in South Africa in November 2021.It showed increased transmissibility and immune evasion with far more amino acid mutations in the spike(S)protein than the previously circulating variants of concern(VOCs).Notably,on 15 July 2022,we monitored the first VOC/Omicron subvariant BA.2.75 in China from an imported case.Moreover,nowadays,this subvariant still is predominant in India.It has nine additional mutations in the S protein compared to BA.2,three of which(W152R,G446S,and R493Q reversion)might contribute to higher transmissibility and immune escape.This subvariant could cause wider spread and pose a threat to the global situation.Our timely reporting and continuous genomic analysis are essential to fully elucidate the characteristics of the subvariant BA.2.75 in the future.展开更多
Infection and vaccination can provide protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the emergence of SARS-CoV-2 variants has persisted, leading to breakthrough infe...Infection and vaccination can provide protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the emergence of SARS-CoV-2 variants has persisted, leading to breakthrough infections. Owing to the original antigenic sin (OAS), variant breakthrough infection or vaccination potentially induces a stronger antibody response against the ancestral strain than to subsequent variants, as in the case of influenza. Thus, overcoming OAS is important for the development of future vaccine designs. This review summarizes the recent findings on OAS in the antibody response to SARS-CoV-2 and its variants, with an emphasis on future vaccine designs.展开更多
Background and Aims:Our aim was to determine the immune efficacy of a severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)booster vaccination in cirrhotic patients who had received the primary series.Methods:We...Background and Aims:Our aim was to determine the immune efficacy of a severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)booster vaccination in cirrhotic patients who had received the primary series.Methods:We performed a longitudinal assessment in 48 patients with cirrhosis,57 patients with chronic hepatitis B(CHB)and 68 healthy controls(HCs)to continuously track the dynamics of SARS-CoV-2 specific antibodies and memory B cells after receiving the primary series and booster dose at different times.A pseudovirus neutralization assay was used to determine neutralization against Omicron subvariants BA.2.12.1,BA.4 and BA.5 from serum samples collected from three cohorts.Results:Serum anti-receptor-binding domain(RBD)immunoglobulin(Ig)G and neutralizing antibody(NAb)levels in cirrhotic patients were elevated within 15–45 days after completing the primary series before rapidly declining and reaching a valley at around 165–195 days.After receiving the booster dose,both antibody levels were significantly increased to levels comparable to patients with CHB and HCs.Subgroup analysis showed that booster vaccination induced weaker antibody responses in patients with decompensated cirrhosis than in those with compensated cirrhosis.The SARS-CoV-2 memory B-cell response in cirrhotic patients was durable during follow-up regardless of the hepatic fibrocirrhosis grade.However,compared with the primary series,the booster dose did not result in an evident improvement of neutralization activity against the Omicron subvariants BA.2.12.1 and BA.4,and was followed by a significant decrease in the titer against BA.5.Conclusions:A booster dose elicited a robust and durable humoral response to the wild-type strain in cirrhotic patients but not the Omicron subvariants.Repeated vaccination of inactivated SARS-CoV-2 vaccine may not benefit cirrhotic patients in neutralization against newly circulating strains.展开更多
Wastewater surveillance plays an important role in the monitoring of infections of SARS-CoV-2 at the community level.We report here the determination of SARS-CoV-2 and differentiation of its variants of concern in 294...Wastewater surveillance plays an important role in the monitoring of infections of SARS-CoV-2 at the community level.We report here the determination of SARS-CoV-2 and differentiation of its variants of concern in 294 wastewater samples collected from two major Canadian cities from May 2021 to March 2023.The overall method of analysis involved extraction of the virus and viral components using electronegative membranes,in situ stabilization and concentration of the viral RNA onto magnetic beads,and direct analysis of the viral RNA on the magnetic beads.Multiplex reverse transcription quantitative polymerase chain reaction(RT-qPCR)assays,targeting specific and naturally selected mutations in SARS-CoV-2,enabled detection and differentiation of the Alpha,Beta,Gamma,Delta,and Omicron variants.An Omicron triplex RT-qPCR assay targeting three mutations,HV 69−70 deletion,K417N,and L452R,was able to detect and differentiate the Omicron BA.1/BA.3,BA.2/XBB,and BA.4/5.This assay had efficiencies of 90−104%for all three mutation targets and a limit of detection of 28 RNA copies per reaction.Analyses of 294 wastewater samples collected over a two-year span showed the concentrations and trends of Alpha,Beta,Gamma,Delta,and Omicron variants as they emerge in two major Canadian cities participating in the wastewater surveillance program.The trends of specific variants were consistent with clinical reports for the same period.At the beginning of each wave,the corresponding variants were detectable in wastewater.For example,RNA concentrations of the BA.2 variant were as high as 10^(4)copies per 100 mL of wastewater collected in January 2022,when approximately only 50−60 clinical cases of BA.2 infection were reported in Canada.These results show that the strategy and highly sensitive assays for the variants of concern in wastewater are potentially useful for the detection of newly emerging SARS-CoV-2 variants and other viruses for future community biomonitoring.展开更多
基金supported by Sinocelltech with grant support from Beijing Municipal Science and Technology Program(Z211100002521026,Z221100007922012)。
文摘Multivalent vaccines combining crucial mutations from phylogenetically divergent variants could be an effective approach to defend against existing and future SARS-Co V-2 variants.In this study,we developed a tetravalent COVID-19 vaccine SCTV01E,based on the trimeric Spike protein of SARS-Co V-2 variants Alpha,Beta,Delta,and Omicron BA.1,with a squalenebased oil-in-water adjuvant SCT-VA02B.In the immunogenicity studies in na?ve BALB/c and C57BL/6J mice,SCTV01E exhibited the most favorable immunogenic characteristics to induce balanced and broad-spectrum neutralizing potencies against pre-Omicron variants(D614G,Alpha,Beta,and Delta)and newly emerging Omicron subvariants(BA.1,BA.1.1,BA.2,BA.3,and BA.4/5).Booster studies in C57BL/6J mice previously immunized with D614G monovalent vaccine demonstrated superior neutralizing capacities of SCTV01E against Omicron subvariants,compared with the D614G booster regimen.Furthermore,SCTV01E vaccination elicited na?ve and central memory T cell responses to SARS-Co V-2 ancestral strain and Omicron spike peptides.Together,our comprehensive immunogenicity evaluation results indicate that SCTV01E could become an important COVID-19 vaccine platform to combat surging infections caused by the highly immune evasive BA.4/5 variants.SCTV01E is currently being studied in a head-to-head immunogenicity comparison phase 3 clinical study with inactivated and m RNA vaccines(NCT05323461).
文摘The Omicron variants spread rapidly worldwide after being initially detected in South Africa in November 2021.It showed increased transmissibility and immune evasion with far more amino acid mutations in the spike(S)protein than the previously circulating variants of concern(VOCs).Notably,on 15 July 2022,we monitored the first VOC/Omicron subvariant BA.2.75 in China from an imported case.Moreover,nowadays,this subvariant still is predominant in India.It has nine additional mutations in the S protein compared to BA.2,three of which(W152R,G446S,and R493Q reversion)might contribute to higher transmissibility and immune escape.This subvariant could cause wider spread and pose a threat to the global situation.Our timely reporting and continuous genomic analysis are essential to fully elucidate the characteristics of the subvariant BA.2.75 in the future.
基金supported by the National Science Fund for Distinguished Young Scholars(82025022)the National Science Fund for Outstanding Young Scholars(82322040)+6 种基金the National Natural Science Foundation of China(92169204,82302494)the Guangdong Science and Technology Plan Project-Construction of High-level Biosafety Laboratories(2021B1212030010)the Guangdong Basic and Applied Basic Research Foundation(2021B1515020034,2023A1515011883)the Shenzhen Science and Technology Program(RCYX20200714114700046,ZDSYS20210623091810030)the Shenzhen Natural Science Foundation(JCYJ20220530163405012)the Chinese Academy of Medical Sciences Clinical and Translational Medicine Research Project(2022-I2M-C&T-B-113)the Shenzhen High-level Hospital Construction Fund(23250G1002).
文摘Infection and vaccination can provide protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the emergence of SARS-CoV-2 variants has persisted, leading to breakthrough infections. Owing to the original antigenic sin (OAS), variant breakthrough infection or vaccination potentially induces a stronger antibody response against the ancestral strain than to subsequent variants, as in the case of influenza. Thus, overcoming OAS is important for the development of future vaccine designs. This review summarizes the recent findings on OAS in the antibody response to SARS-CoV-2 and its variants, with an emphasis on future vaccine designs.
基金supported by the National Science and Technology Major Project of China(2017ZX10202203-007,2017 ZX10202203-008,2018ZX10302206-003)Remarkable Innovation-Clinical Research Project,The Second Affiliated Hospital of Chongqing Medical University and The First batch of key Disciplines On Public Health in Chongqing+1 种基金support of the National Natural Science Foundation of China(81772198)Natural Science Foundation of Chongqing,China(cstc2020jcyj-msxmX0389).
文摘Background and Aims:Our aim was to determine the immune efficacy of a severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)booster vaccination in cirrhotic patients who had received the primary series.Methods:We performed a longitudinal assessment in 48 patients with cirrhosis,57 patients with chronic hepatitis B(CHB)and 68 healthy controls(HCs)to continuously track the dynamics of SARS-CoV-2 specific antibodies and memory B cells after receiving the primary series and booster dose at different times.A pseudovirus neutralization assay was used to determine neutralization against Omicron subvariants BA.2.12.1,BA.4 and BA.5 from serum samples collected from three cohorts.Results:Serum anti-receptor-binding domain(RBD)immunoglobulin(Ig)G and neutralizing antibody(NAb)levels in cirrhotic patients were elevated within 15–45 days after completing the primary series before rapidly declining and reaching a valley at around 165–195 days.After receiving the booster dose,both antibody levels were significantly increased to levels comparable to patients with CHB and HCs.Subgroup analysis showed that booster vaccination induced weaker antibody responses in patients with decompensated cirrhosis than in those with compensated cirrhosis.The SARS-CoV-2 memory B-cell response in cirrhotic patients was durable during follow-up regardless of the hepatic fibrocirrhosis grade.However,compared with the primary series,the booster dose did not result in an evident improvement of neutralization activity against the Omicron subvariants BA.2.12.1 and BA.4,and was followed by a significant decrease in the titer against BA.5.Conclusions:A booster dose elicited a robust and durable humoral response to the wild-type strain in cirrhotic patients but not the Omicron subvariants.Repeated vaccination of inactivated SARS-CoV-2 vaccine may not benefit cirrhotic patients in neutralization against newly circulating strains.
文摘Wastewater surveillance plays an important role in the monitoring of infections of SARS-CoV-2 at the community level.We report here the determination of SARS-CoV-2 and differentiation of its variants of concern in 294 wastewater samples collected from two major Canadian cities from May 2021 to March 2023.The overall method of analysis involved extraction of the virus and viral components using electronegative membranes,in situ stabilization and concentration of the viral RNA onto magnetic beads,and direct analysis of the viral RNA on the magnetic beads.Multiplex reverse transcription quantitative polymerase chain reaction(RT-qPCR)assays,targeting specific and naturally selected mutations in SARS-CoV-2,enabled detection and differentiation of the Alpha,Beta,Gamma,Delta,and Omicron variants.An Omicron triplex RT-qPCR assay targeting three mutations,HV 69−70 deletion,K417N,and L452R,was able to detect and differentiate the Omicron BA.1/BA.3,BA.2/XBB,and BA.4/5.This assay had efficiencies of 90−104%for all three mutation targets and a limit of detection of 28 RNA copies per reaction.Analyses of 294 wastewater samples collected over a two-year span showed the concentrations and trends of Alpha,Beta,Gamma,Delta,and Omicron variants as they emerge in two major Canadian cities participating in the wastewater surveillance program.The trends of specific variants were consistent with clinical reports for the same period.At the beginning of each wave,the corresponding variants were detectable in wastewater.For example,RNA concentrations of the BA.2 variant were as high as 10^(4)copies per 100 mL of wastewater collected in January 2022,when approximately only 50−60 clinical cases of BA.2 infection were reported in Canada.These results show that the strategy and highly sensitive assays for the variants of concern in wastewater are potentially useful for the detection of newly emerging SARS-CoV-2 variants and other viruses for future community biomonitoring.
