Objective:To evaluate the immunological response elicited by an inactivated bacterial vector carrying the K39 antigen of Leishmania infantum,and a purified antigen.Methods:Mice were subjected to the following treatmen...Objective:To evaluate the immunological response elicited by an inactivated bacterial vector carrying the K39 antigen of Leishmania infantum,and a purified antigen.Methods:Mice were subjected to the following treatments:(1)Purified recombinant K39(rK39)protein at a 20μg dose with complete Freund’s adjuvant;(2)Inactivated Escherichia coli(BL21 DE3)carrying the K39 protein at an equivalent total protein content of 200μg;(3)Inactivated bacteria lacking the K39 protein;(4)Non-immunized control animals.Serological monitoring was performed.All groups were challenged by intraperitoneal injection of 10^(7) Leishmania infantum promastigotes.After euthanasia,the liver and spleen were collected to analyze the levels of TNF,IFN-γ,IL-12,IL-4,and IL-10.Results:Mice immunized with purified rK39 or the inactivated bacterial vector carrying the K39 antigen of Leishmania infantum showed a long-lasting immune response with high levels of polyclonal antibodies specifically recognizing the recombinant proteins.The IgG1 subclass was the predominant immunoglobulin;however,the induction of IgG2a and the profile of cytokines produced were indicative of the induction of a mixed-type response.Conclusions:The inactivated bacterial vector carrying the K39 antigen,as well as the purified antigen can induce a long-lasting immune response in immunized mice,predominantly favouring a Th2 profile response.展开更多
Anti-cancer therapies over the few decades, faced with many challenges. And bacterial vaccine vectors have shown a potential to be replaced as the cutting-edge technology for such aspects. Bacterial vaccine vectors wi...Anti-cancer therapies over the few decades, faced with many challenges. And bacterial vaccine vectors have shown a potential to be replaced as the cutting-edge technology for such aspects. Bacterial vaccine vectors with a suitable DNA can be a potential option for cancer treatment as a carrier for tumoricidal agents or bacterially directed Enzyme Prodrug treatment. Throughout this study, it is planned to have a review of the use of bacteria as vehicles by different ways for cancer treatment, detailing the systems of function and achievements at preclinical and clinical levels.展开更多
Fusobacterium nucleatum(F.nucleatum),an oral anaerobe,is prevalent in colorectal cancer and is closely related to increased cancer cell growth,metastasis,and poor treatment outcomes.Bacterial vaccines capable of selec...Fusobacterium nucleatum(F.nucleatum),an oral anaerobe,is prevalent in colorectal cancer and is closely related to increased cancer cell growth,metastasis,and poor treatment outcomes.Bacterial vaccines capable of selectively eliminating bacteria present a promising approach to targeting intratumor F.nucleatum,thereby enhancing cancer treatment.Although adjuvants have been employed to enhance the immune response,the vaccine’s effectiveness is constrained by inadequate T-cell activation necessary for eradicating intracellular pathogens.In this study,we developed a minimalistic,biomimetic nanovaccine by integrating highly immunostimulatory adjuvant cholesterol-modified CpG oligonucleotides into the autologously derived F.nucleatum membranes.Compared to the traditional vaccines consisting of inactivated bacteria and Alum adjuvant,the nanovaccine coupled with bacterial membranes and adjuvants could remarkably improve multiple antigens and adjuvant co-delivery to dendritic cells,maximizing their ability to achieve effective antigen presentation and strong downstream immune progress.Notably,the nanovaccine exhibits outstanding selective prophylactic and therapeutic effects,eliminating F.nucleatum without affecting intratumoral and gut microbiota.It significantly enhances chemotherapy efficacy and reduces cancer metastasis in F.nucleatum-infected colorectal cancer.Overall,this work represents the rational application of bacterial nanovaccine and provides a blueprint for future development in enhancing the antitumor effect against bacterial-infected cancer.展开更多
Objective: To refine the infectious doses of enteric bacterial pathogens in animal assays and vaccine clinical trials by studying the invasion kinetics of five bacterial pathogens with human intestinal cells.Methods: ...Objective: To refine the infectious doses of enteric bacterial pathogens in animal assays and vaccine clinical trials by studying the invasion kinetics of five bacterial pathogens with human intestinal cells.Methods: Utilizing in vitro cultured cell invasion assays with gentamicin-killing step,the invasive effects were analyzed in foodborne pathogens including Salmonella,Shigella, Yersinia, Escherichia coli(E. coli) O157 and opportunistic pathogens Citrobacter in human embryonic intestine 407 cells and ileocecum HCT-8 cells at multiplicities of infection(MOIs) of 0.04–4 000.00 E. coli HS served as a noninvasive control.Results: The study results showed that the bacterial invasive efficiency and the average number of internalized bacteria per host cell changed with different starting MOIs. Higher starting MOIs did not always produce more bacterial internalization. The bacterial invasion effects varied with different bacterial strains and host cell lines. E. coli O157:H7 did invade human ileocecum HCT-8 cells.Conclusions: This study shows that these bacteria possess different invasive patterns at various starting MOIs and also in different cell lines. The results could help to figure out the appropriate infectious doses of the bacteria in animal assays and in vaccine clinical trials. The bacterial invasion kinetics is also valuable in evaluating the safety and efficacy of live attenuated bacterial vaccines.展开更多
DNA vaccines are the third generation vaccines based on purified plasmid preparations containing transgenes that encode antigenic/therapeutic proteins or peptides capable of triggering an immune response against a wid...DNA vaccines are the third generation vaccines based on purified plasmid preparations containing transgenes that encode antigenic/therapeutic proteins or peptides capable of triggering an immune response against a wide range of diseases. This vaccine platform presents several attributes that confer distinct advantages over other vaccine technologies in terms of safety, ease of fabrication and stability. Many aspects, such as antigen expression and especially vector design, are under study because of their great influence on immunogenicity and efficacy of DNA vaccines. In this regard, with the attempt of improving the efficiency of DNA vaccines, co-expression of stimulatory sequences and diverse vector delivery systems are being optimized. With this in mind, this review aims to giving a conceptual approach of DNA vaccines, explaining their mechanisms of action and listing the already licensed veterinary DNA vaccines presented in the market.展开更多
Objective: To evaluate the effects of Pasteurella multocida(P. multocida) vaccines on the expression and release of antibodies, interleukin(IL)-6 and IL-12 by serum. Methods: Balb/c mice were immunized with two formal...Objective: To evaluate the effects of Pasteurella multocida(P. multocida) vaccines on the expression and release of antibodies, interleukin(IL)-6 and IL-12 by serum. Methods: Balb/c mice were immunized with two formalin and iron inactivated vaccine doses within 2 weeks. The vaccines were adjuvant with P. multocida A strain, P. multocida B strain and Salmonella typhimurium bacterial DNA(AbDNA, BbDNA and SbDNA for short, respectively). The animals were challenged 4 weeks after immunization. Blood of mice was collected to detect the change of specific antibody, IL-6, and IL-12 using ELISA. Results: The specific antibody and interleukins in the immunized group increased significantly compared to the control mice after vaccination and challenge(P<0.05). The highest release of these cytokines was obtained by P.multocida inactivated with iron and adjuvant with AbDNA at a concentration of 25 μg/mL. The antibody titer peak was 0.447 in mice vaccinated with iron-killed whole-cell antigen adjunct with AbDNA. The time-courses of release showed that bacterial DNA was able to stimulate IL-6 and IL-12 production more than alum(P<0.05). Conclusions: Our findings introduce that bacterial DNA is capable of releasing an immunological response with several cytokines.These indicate that bacterial DNA entrapped with killed P. multocida antigen is a new and effective adjuvant to enhance specific immunity and resistance of animal against the infectious pathogen, which could simplify the development of highly promising strong adjuvant.展开更多
Regardless of etiology,complications with bacterial infection in patients with cirrhosis are reported in the range of 25%-46%according to the most recent data.Due to frequent episodes of bacterial infection and repeti...Regardless of etiology,complications with bacterial infection in patients with cirrhosis are reported in the range of 25%-46%according to the most recent data.Due to frequent episodes of bacterial infection and repetitive antibiotic treatment,most often with broad-spectrum gram negative coverage,patients with cirrhosis are at increased risk of encountering multidrug resistant bacteria,and this raises concern.In such patients,extended-spectrum beta-lactamase and AmpCproducing Enterobacterales,methicillin-or vancomycin-resistant Staphylococcus aureus,vancomycin-resistant Enterococci,carbapenem-resistant Pseudomonas aeruginosa,and Acinetobacter baumannii,all of which are difficult to treat,are the most common.That is why novel approaches to the prophylaxis and treatment of bacterial infections to avoid antibiotic resistance have recently been developed.At the same time,our knowledge of resistance mechanisms is constantly updated.This review summarizes the current situation regarding the burden of antibiotic resistance,including the prevalence and mechanisms of intrinsic and acquired resistance in bacterial species that most frequently cause complications in patients with liver cirrhosis and recent developments on how to deal with multidrug resistant bacteria.展开更多
基金supported by grants from the Brazilian Agencies:Coordenação de Aperfeiçoamento de Pessoal de Nível Superior(CAPES-Financial code 001)Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico(FUNCAP).
文摘Objective:To evaluate the immunological response elicited by an inactivated bacterial vector carrying the K39 antigen of Leishmania infantum,and a purified antigen.Methods:Mice were subjected to the following treatments:(1)Purified recombinant K39(rK39)protein at a 20μg dose with complete Freund’s adjuvant;(2)Inactivated Escherichia coli(BL21 DE3)carrying the K39 protein at an equivalent total protein content of 200μg;(3)Inactivated bacteria lacking the K39 protein;(4)Non-immunized control animals.Serological monitoring was performed.All groups were challenged by intraperitoneal injection of 10^(7) Leishmania infantum promastigotes.After euthanasia,the liver and spleen were collected to analyze the levels of TNF,IFN-γ,IL-12,IL-4,and IL-10.Results:Mice immunized with purified rK39 or the inactivated bacterial vector carrying the K39 antigen of Leishmania infantum showed a long-lasting immune response with high levels of polyclonal antibodies specifically recognizing the recombinant proteins.The IgG1 subclass was the predominant immunoglobulin;however,the induction of IgG2a and the profile of cytokines produced were indicative of the induction of a mixed-type response.Conclusions:The inactivated bacterial vector carrying the K39 antigen,as well as the purified antigen can induce a long-lasting immune response in immunized mice,predominantly favouring a Th2 profile response.
文摘Anti-cancer therapies over the few decades, faced with many challenges. And bacterial vaccine vectors have shown a potential to be replaced as the cutting-edge technology for such aspects. Bacterial vaccine vectors with a suitable DNA can be a potential option for cancer treatment as a carrier for tumoricidal agents or bacterially directed Enzyme Prodrug treatment. Throughout this study, it is planned to have a review of the use of bacteria as vehicles by different ways for cancer treatment, detailing the systems of function and achievements at preclinical and clinical levels.
基金partially supported by the National Research Programs of China(2022YFA1206500 and 2020YFA0211100)the National Natural Science Foundation of China(52172285 and 52325106)+1 种基金the Suzhou Key Laboratory of Nanotechnology and Biomedicine,the Collaborative Innovation Centre of Suzhou Nano Science and Technologythe 111 Program from the Ministry of Education of China.
文摘Fusobacterium nucleatum(F.nucleatum),an oral anaerobe,is prevalent in colorectal cancer and is closely related to increased cancer cell growth,metastasis,and poor treatment outcomes.Bacterial vaccines capable of selectively eliminating bacteria present a promising approach to targeting intratumor F.nucleatum,thereby enhancing cancer treatment.Although adjuvants have been employed to enhance the immune response,the vaccine’s effectiveness is constrained by inadequate T-cell activation necessary for eradicating intracellular pathogens.In this study,we developed a minimalistic,biomimetic nanovaccine by integrating highly immunostimulatory adjuvant cholesterol-modified CpG oligonucleotides into the autologously derived F.nucleatum membranes.Compared to the traditional vaccines consisting of inactivated bacteria and Alum adjuvant,the nanovaccine coupled with bacterial membranes and adjuvants could remarkably improve multiple antigens and adjuvant co-delivery to dendritic cells,maximizing their ability to achieve effective antigen presentation and strong downstream immune progress.Notably,the nanovaccine exhibits outstanding selective prophylactic and therapeutic effects,eliminating F.nucleatum without affecting intratumoral and gut microbiota.It significantly enhances chemotherapy efficacy and reduces cancer metastasis in F.nucleatum-infected colorectal cancer.Overall,this work represents the rational application of bacterial nanovaccine and provides a blueprint for future development in enhancing the antitumor effect against bacterial-infected cancer.
文摘Objective: To refine the infectious doses of enteric bacterial pathogens in animal assays and vaccine clinical trials by studying the invasion kinetics of five bacterial pathogens with human intestinal cells.Methods: Utilizing in vitro cultured cell invasion assays with gentamicin-killing step,the invasive effects were analyzed in foodborne pathogens including Salmonella,Shigella, Yersinia, Escherichia coli(E. coli) O157 and opportunistic pathogens Citrobacter in human embryonic intestine 407 cells and ileocecum HCT-8 cells at multiplicities of infection(MOIs) of 0.04–4 000.00 E. coli HS served as a noninvasive control.Results: The study results showed that the bacterial invasive efficiency and the average number of internalized bacteria per host cell changed with different starting MOIs. Higher starting MOIs did not always produce more bacterial internalization. The bacterial invasion effects varied with different bacterial strains and host cell lines. E. coli O157:H7 did invade human ileocecum HCT-8 cells.Conclusions: This study shows that these bacteria possess different invasive patterns at various starting MOIs and also in different cell lines. The results could help to figure out the appropriate infectious doses of the bacteria in animal assays and in vaccine clinical trials. The bacterial invasion kinetics is also valuable in evaluating the safety and efficacy of live attenuated bacterial vaccines.
文摘DNA vaccines are the third generation vaccines based on purified plasmid preparations containing transgenes that encode antigenic/therapeutic proteins or peptides capable of triggering an immune response against a wide range of diseases. This vaccine platform presents several attributes that confer distinct advantages over other vaccine technologies in terms of safety, ease of fabrication and stability. Many aspects, such as antigen expression and especially vector design, are under study because of their great influence on immunogenicity and efficacy of DNA vaccines. In this regard, with the attempt of improving the efficiency of DNA vaccines, co-expression of stimulatory sequences and diverse vector delivery systems are being optimized. With this in mind, this review aims to giving a conceptual approach of DNA vaccines, explaining their mechanisms of action and listing the already licensed veterinary DNA vaccines presented in the market.
基金part of the project:Study on immune response pattern of cattle vaccinated by Razi pasteurellosis vaccine(Project number:12-18-18-9458-94014)
文摘Objective: To evaluate the effects of Pasteurella multocida(P. multocida) vaccines on the expression and release of antibodies, interleukin(IL)-6 and IL-12 by serum. Methods: Balb/c mice were immunized with two formalin and iron inactivated vaccine doses within 2 weeks. The vaccines were adjuvant with P. multocida A strain, P. multocida B strain and Salmonella typhimurium bacterial DNA(AbDNA, BbDNA and SbDNA for short, respectively). The animals were challenged 4 weeks after immunization. Blood of mice was collected to detect the change of specific antibody, IL-6, and IL-12 using ELISA. Results: The specific antibody and interleukins in the immunized group increased significantly compared to the control mice after vaccination and challenge(P<0.05). The highest release of these cytokines was obtained by P.multocida inactivated with iron and adjuvant with AbDNA at a concentration of 25 μg/mL. The antibody titer peak was 0.447 in mice vaccinated with iron-killed whole-cell antigen adjunct with AbDNA. The time-courses of release showed that bacterial DNA was able to stimulate IL-6 and IL-12 production more than alum(P<0.05). Conclusions: Our findings introduce that bacterial DNA is capable of releasing an immunological response with several cytokines.These indicate that bacterial DNA entrapped with killed P. multocida antigen is a new and effective adjuvant to enhance specific immunity and resistance of animal against the infectious pathogen, which could simplify the development of highly promising strong adjuvant.
文摘Regardless of etiology,complications with bacterial infection in patients with cirrhosis are reported in the range of 25%-46%according to the most recent data.Due to frequent episodes of bacterial infection and repetitive antibiotic treatment,most often with broad-spectrum gram negative coverage,patients with cirrhosis are at increased risk of encountering multidrug resistant bacteria,and this raises concern.In such patients,extended-spectrum beta-lactamase and AmpCproducing Enterobacterales,methicillin-or vancomycin-resistant Staphylococcus aureus,vancomycin-resistant Enterococci,carbapenem-resistant Pseudomonas aeruginosa,and Acinetobacter baumannii,all of which are difficult to treat,are the most common.That is why novel approaches to the prophylaxis and treatment of bacterial infections to avoid antibiotic resistance have recently been developed.At the same time,our knowledge of resistance mechanisms is constantly updated.This review summarizes the current situation regarding the burden of antibiotic resistance,including the prevalence and mechanisms of intrinsic and acquired resistance in bacterial species that most frequently cause complications in patients with liver cirrhosis and recent developments on how to deal with multidrug resistant bacteria.
