Soy sauce by a high salt liquid-state fermentation process was prepared using the organic soy beans as raw material. Beidahuang organic soy bean was selected among different raw materials. Here, the best technique was...Soy sauce by a high salt liquid-state fermentation process was prepared using the organic soy beans as raw material. Beidahuang organic soy bean was selected among different raw materials. Here, the best technique was determined. Firstly, the organic soy beans were soaked for 7 hours under 121℃, steamed for 15 min and mixed with the fried wheat (5:5, w/w). After inoculated with Aspergillus oryzae 3.042 (0.3%, w/w) and cultured for 36 hours, the koji was obtained. When the brine (2:1, w/w) was added, fermentation started. At the end of the fermentation, isoflavone content of organic soy sauce was 0.22 mg· g-1 higher than those in the non- organic soy beans. In addition, compared to the control there were a higher unsaturated fatty acids content, the linoleic acid content in crude fat of 51.61% and γ-linolenic acid content in crude fat of 0.55%.展开更多
Recombinant adenovirus serotype 5(Ad5)vector has been widely applied in vaccine development targeting infectious diseases,such as Ebola virus disease and coronavirus disease 2019(COVID-19).However,the high prevalence ...Recombinant adenovirus serotype 5(Ad5)vector has been widely applied in vaccine development targeting infectious diseases,such as Ebola virus disease and coronavirus disease 2019(COVID-19).However,the high prevalence of preexisting anti-vector immunity compromises the immunogenicity of Ad5-based vaccines.Thus,there is a substantial unmet need to minimize preexisting immunity while improving the insert-induced immunity of Ad5 vectors.Herein,we address this need by utilizing biocompatible nanoparticles to modulate Ad5–host interactions.We show that positively charged human serum albumin nanoparticles((+)HSAnp),which are capable of forming a complex with Ad5,significantly increase the transgene expression of Ad5 in both coxsackievirus–adenovirus receptor-positive and-negative cells.Furthermore,in charge-and dose-dependent manners,Ad5/(+)HSAnp complexes achieve robust(up to227-fold higher)and long-term(up to 60 days)transgene expression in the lungs of mice following intranasal instillation.Importantly,in the presence of preexisting anti-Ad5 immunity,complexed Ad5-based Ebola and COVID-19 vaccines significantly enhance antigen-specific humoral response and mucosal immunity.These findings suggest that viral aggregation and charge modification could be leveraged to engineer enhanced viral vectors for vaccines and gene therapies.展开更多
The vaccine-induced innate immune response is essential for the generation of an antibody response.To date,how Ad5-vectored vaccines are influenced by preexisting anti-Ad5 antibodies during activation of the early imm...The vaccine-induced innate immune response is essential for the generation of an antibody response.To date,how Ad5-vectored vaccines are influenced by preexisting anti-Ad5 antibodies during activation of the early immune response remains unclear.Here,we investigated the specific alterations in GP1,2-specific IgG-related elements of the early immune response at the genetic,molecular,and cellular levels on days 0,1,3,and 7 after Ad5-EBOV vaccination.In a causal multiomics analysis,distinct early immune responses associated with GP1,2-specific IgG were observed in Ad5-EBOV recipients with a low level of preexisting anti-Ad5 antibodies.This study revealed the correlates of the Ad5-EBOV-induced IgG response and provided mechanistic evidence for overcoming preexisting Ad5 immunity during the administration of Ad5-vectored vaccines.展开更多
Dear Editor,In the era of COVID-19,the prevalence of viruses from other families poses new threats to humans.Despite the eradication of smallpox in 1980,the global outbreak of monkeypox in 2022(Lum et al.,2022;Nuzzo e...Dear Editor,In the era of COVID-19,the prevalence of viruses from other families poses new threats to humans.Despite the eradication of smallpox in 1980,the global outbreak of monkeypox in 2022(Lum et al.,2022;Nuzzo et al.,2022)alerted that the re-emerging orthopoxvirus(OPXV)remained a persistent threat to global health.OPXV includes a number of viruses with a broad host range,including variola virus(VARV),monkeypox virus(MPXV),vaccinia virus(VACV).展开更多
Highly divergent SARS-CoV-2 variants have continuously emerged and spread around the world,and updated vaccines and innovative vaccination strategies are urgently needed to address the global SARS-COV2 pandemic.Here,w...Highly divergent SARS-CoV-2 variants have continuously emerged and spread around the world,and updated vaccines and innovative vaccination strategies are urgently needed to address the global SARS-COV2 pandemic.Here,we established a series of Ad5-vectored SARS-CoV-2 variant vaccines encoding multiple spike proteins derived from the Alpha,Beta,Gamma,Epsilon,Kappa,Delta and Omicron lineages and analyzed the antibody immune responses induced by single-dose and prime-boost vaccination strategies against emerging SARS-CoV-2 variants of concern(VOCs).Single-dose vaccination with SARS-CoV-2 variant vaccines tended to elicit the optimal self-matched neutralizing effects,and Ad5-B.1.351 produced more broad-spectrum cross-neutralizing antibodies against diverse variants.In contrast,prime-boost vaccination further strengthened and broadened the neutralizing antibody responses against highly divergent SARS-CoV-2 variants.The heterologous administration of Ad5-B.1.617.2 and Ad5-B.1.429 to Ad5-WT-primed mice resulted in superior antibody responses against most VOCs.In particular,the Omicron spike could only stimulate self-matched neutralizing antibodies with infrequent cross-reactivities to other variants used in single-dose vaccination strategies;moreover,with prime-boost regimens,this vaccine elicited an optimal specific neutralizing antibody response to Omicron,and prompted cross-antibody responses against other VOCs that were very similar to those obtained with Ad5-WT booster.Overall,this study delineated the unique characteristics of antibody responses to the SARS-CoV-2 VOC spikes with the single-dose or prime-boost vaccination strategies and provided insight into the vaccine development of next SARS-CoV-2 VOCs.展开更多
文摘Soy sauce by a high salt liquid-state fermentation process was prepared using the organic soy beans as raw material. Beidahuang organic soy bean was selected among different raw materials. Here, the best technique was determined. Firstly, the organic soy beans were soaked for 7 hours under 121℃, steamed for 15 min and mixed with the fried wheat (5:5, w/w). After inoculated with Aspergillus oryzae 3.042 (0.3%, w/w) and cultured for 36 hours, the koji was obtained. When the brine (2:1, w/w) was added, fermentation started. At the end of the fermentation, isoflavone content of organic soy sauce was 0.22 mg· g-1 higher than those in the non- organic soy beans. In addition, compared to the control there were a higher unsaturated fatty acids content, the linoleic acid content in crude fat of 51.61% and γ-linolenic acid content in crude fat of 0.55%.
基金supported in part by the grant from National Natural Science Foundation of China(82171818,81703048,82041019,and 82101919)the grant from Defense Industrial Technology Development Program of China(JCKY2020802B001)Beijing Municipal Science and Technology Commission(Z201100005420024)。
文摘Recombinant adenovirus serotype 5(Ad5)vector has been widely applied in vaccine development targeting infectious diseases,such as Ebola virus disease and coronavirus disease 2019(COVID-19).However,the high prevalence of preexisting anti-vector immunity compromises the immunogenicity of Ad5-based vaccines.Thus,there is a substantial unmet need to minimize preexisting immunity while improving the insert-induced immunity of Ad5 vectors.Herein,we address this need by utilizing biocompatible nanoparticles to modulate Ad5–host interactions.We show that positively charged human serum albumin nanoparticles((+)HSAnp),which are capable of forming a complex with Ad5,significantly increase the transgene expression of Ad5 in both coxsackievirus–adenovirus receptor-positive and-negative cells.Furthermore,in charge-and dose-dependent manners,Ad5/(+)HSAnp complexes achieve robust(up to227-fold higher)and long-term(up to 60 days)transgene expression in the lungs of mice following intranasal instillation.Importantly,in the presence of preexisting anti-Ad5 immunity,complexed Ad5-based Ebola and COVID-19 vaccines significantly enhance antigen-specific humoral response and mucosal immunity.These findings suggest that viral aggregation and charge modification could be leveraged to engineer enhanced viral vectors for vaccines and gene therapies.
基金National Natural Science Foundation of China 31900671.
文摘The vaccine-induced innate immune response is essential for the generation of an antibody response.To date,how Ad5-vectored vaccines are influenced by preexisting anti-Ad5 antibodies during activation of the early immune response remains unclear.Here,we investigated the specific alterations in GP1,2-specific IgG-related elements of the early immune response at the genetic,molecular,and cellular levels on days 0,1,3,and 7 after Ad5-EBOV vaccination.In a causal multiomics analysis,distinct early immune responses associated with GP1,2-specific IgG were observed in Ad5-EBOV recipients with a low level of preexisting anti-Ad5 antibodies.This study revealed the correlates of the Ad5-EBOV-induced IgG response and provided mechanistic evidence for overcoming preexisting Ad5 immunity during the administration of Ad5-vectored vaccines.
基金supported in part by Beijing Nova Program of Science and Technology(20220484127)National Natural Science Foundation of China(82171818)。
文摘Dear Editor,In the era of COVID-19,the prevalence of viruses from other families poses new threats to humans.Despite the eradication of smallpox in 1980,the global outbreak of monkeypox in 2022(Lum et al.,2022;Nuzzo et al.,2022)alerted that the re-emerging orthopoxvirus(OPXV)remained a persistent threat to global health.OPXV includes a number of viruses with a broad host range,including variola virus(VARV),monkeypox virus(MPXV),vaccinia virus(VACV).
基金supported by grants from the National Natural Science Foundation of China(82041019 and 82101919)the Beijing Municipal Science and Technology Commission(Z201100005420024).
文摘Highly divergent SARS-CoV-2 variants have continuously emerged and spread around the world,and updated vaccines and innovative vaccination strategies are urgently needed to address the global SARS-COV2 pandemic.Here,we established a series of Ad5-vectored SARS-CoV-2 variant vaccines encoding multiple spike proteins derived from the Alpha,Beta,Gamma,Epsilon,Kappa,Delta and Omicron lineages and analyzed the antibody immune responses induced by single-dose and prime-boost vaccination strategies against emerging SARS-CoV-2 variants of concern(VOCs).Single-dose vaccination with SARS-CoV-2 variant vaccines tended to elicit the optimal self-matched neutralizing effects,and Ad5-B.1.351 produced more broad-spectrum cross-neutralizing antibodies against diverse variants.In contrast,prime-boost vaccination further strengthened and broadened the neutralizing antibody responses against highly divergent SARS-CoV-2 variants.The heterologous administration of Ad5-B.1.617.2 and Ad5-B.1.429 to Ad5-WT-primed mice resulted in superior antibody responses against most VOCs.In particular,the Omicron spike could only stimulate self-matched neutralizing antibodies with infrequent cross-reactivities to other variants used in single-dose vaccination strategies;moreover,with prime-boost regimens,this vaccine elicited an optimal specific neutralizing antibody response to Omicron,and prompted cross-antibody responses against other VOCs that were very similar to those obtained with Ad5-WT booster.Overall,this study delineated the unique characteristics of antibody responses to the SARS-CoV-2 VOC spikes with the single-dose or prime-boost vaccination strategies and provided insight into the vaccine development of next SARS-CoV-2 VOCs.