Over the last decade, there has been a flurry of research on adjuvants for vaccines, and several novel adjuvants are now licensed products or in late stage clinical development. The success of adjuvants in enhancing t...Over the last decade, there has been a flurry of research on adjuvants for vaccines, and several novel adjuvants are now licensed products or in late stage clinical development. The success of adjuvants in enhancing the immune response to antigens has led many researchers to re-focus their vaccine development programs. Although several vaccine candidates have been tested against leishmaniasis, there is yet no effective vaccine against this parasitic disease. Recent research has documented that efforts to develop effective Leishmania vaccine have been limited due to lack of an appropriate adjuvant. In view of this, this review paper outlines some of the adjuvants that have been used in Leishmania vaccine candidates and cites a few of the responses obtained from these studies. The aim of the present review is to consolidate these findings to facilitate the application of these adjuvants in general and experimental vaccinology.展开更多
Porcine reproductive and respiratory syndrome (PRRS) is a devastating disease caused by the PRRS virus. The MontanideTM class of flexible polymeric adjuvants has recently been shown to enhance protective immunity agai...Porcine reproductive and respiratory syndrome (PRRS) is a devastating disease caused by the PRRS virus. The MontanideTM class of flexible polymeric adjuvants has recently been shown to enhance protective immunity against PRRSV infection in piglets when used in combination with PRRS modified live vaccines (MLV). In this study, we explored the efficacy and immunological mechanisms of protection of MontanideTM Gel01 ST (Gel01) adjuvanted modified live PRRSV vaccine in pigs challenged with two genetically distinct strains of PRRSV. Gel01-MLV reduced lymph node pathology scores in pigs challenged with VR-2332 (parental strain of MLV vaccine) but not that in pigs challenged with MN184A (heterologous strain), when compared to that in pigs vaccinated with un-adjuvanted MLV. Pigs vaccinated with Gel01-MLV had higher levels of PRRS-specific antibodies, as measured by IDEXX ELISA and virus neutralizing antibodies, after vaccination and VR-2332 challenge. In addition, pigs vaccinated with Gel01-MLV had decreased levels of IFN-γ, IL-10, and T-regulatory lymphocytes in the blood as compared to that in pigs vaccinated with MLV alone. Interestingly, we found that addition of Gel01 did not change the profile of other T lymphocyte populations after PRRSV challenge. These results demonstrate that the MLV adjuvanted with Gel01 provides enhanced protection against homologous PRRSV infection, possibly by regulating the production of PRRSV-specific antibodies and cytokines involved in the development of T-regulatory cells. Thus, Gel01 ST is a promising adjuvant that can be formulated with PRRSV MLV vaccines to reduce disease severity and tissue damage caused by PRRSV infection in pigs.展开更多
Interleukine-2(IL-2) is a growth factor for antigen-stimulated T lymphocytes and is responsible for ~T-cell clonal expansion after antigen recognition. It has been demonstrated that DNA vaccine-elicited immune respons...Interleukine-2(IL-2) is a growth factor for antigen-stimulated T lymphocytes and is responsible for ~T-cell clonal expansion after antigen recognition. It has been demonstrated that DNA vaccine-elicited immune responses in mice could be augmented substantially by using either an IL-2 protein or a plasmid expressing ~IL-2. Twenty mice, divided into four experimental groups, were immunized with: (1) sham plasmid; ^(2) HIV-1 DNA vaccine alone; (3) HIV-1 DNA vaccine and IL-2 protein; or (4) HIV-1 DNA vaccine and IL-2 plasmid, separately. All the groups were immunized 3 times at a 2-week interval. Fourteen days after the last DNA vaccine injection, recombinant MVA was injected into all the mice except those in group 1. ELISA and ELISPOT were employed to investigate the effect of IL-2 on DNA vaccine immune responses. The obtained results strongly indicate that the efficacy of HIV vaccine can be enhanced by co-administration of a plasmid encoding IL-2.展开更多
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
Leishmaniasis is a disease that ranges in severity infection. Resistance to infection is associated with from skin lesions to serious disfigurement and fatal systemic a T-helper-1 immune response that activates macrop...Leishmaniasis is a disease that ranges in severity infection. Resistance to infection is associated with from skin lesions to serious disfigurement and fatal systemic a T-helper-1 immune response that activates macrophages to kill the intracellular parasite in a nitric oxide-dependent manner. Conversely, disease progression is generally associated with a T-helper-2 response that activates humoral immunity. Current control is based on chemothera- peutic treatments which are expensive, toxic and associated with high relapse and resistance rates. Vaccination remains the best hope for control of all forms of the disease, and the development of a safe, effective and affordable antileishmanial vaccine is a critical global public-health priority. Extensive evidence from studies in animal models indicates that solid protection can be achieved by immunization with defined subunit vaccines or live-at- tenuated strains of Leishmania. However, to date, no vaccine is available despite substantial efforts by many laboratories. Major impediments in Leishmania vaccine development include： lack of adequate funding from national and international agencies, problems related to the translation of data from animal models to human disease, and the transition from the laboratory to the field. Furthermore, a thorough understanding of protective immune responses and generation and maintenance of the immunological memory, an important but least-studied aspect of antiparasitic vaccine development, during Leishmania infection is needed. This review focuses on the progress of the search for an effective vaccine against human and canine leishmaniasis.展开更多
The development of a safe and effective adjuvant that amplifies the immune response to an antigen is important for vaccine delivery. In this study, we developed pristine mesoporous carbon hollow spheres as high-capaci...The development of a safe and effective adjuvant that amplifies the immune response to an antigen is important for vaccine delivery. In this study, we developed pristine mesoporous carbon hollow spheres as high-capacity vaccine protein nanocarriers and safe adjuvants for boosting the immune response. Mono-dispersed invaginated mesostructured hollow carbon spheres （IMHCSs） have an average particle size of -200 nm, large pore size of 15 rim, and high pore volume of 2.85 cmB.g-1. IMHCSs exhibited a very high loading capacity （1,040 ~tg-mg-1） towards ovalbumin （OVA, a model antigen）, controlled OVA release behavior, excellent safety profile to normal cells, and high antigen delivery efficacy towards macrophages. In vivo immunization studies in mice demonstrated that OVA-loaded IMHCSs induced a 3-fold higher IgG response compared to a traditional adjuvant QuilA used in veterinary vaccine research. OVA delivered by IMHCSs induced a higher IgG1 concentration than IgG2a, indicating a T-helper 2 （Th2）-polarized response. Interferon-y and interleukin-4 concentration analysis revealed both T-helper 1 （Thl） and Th2 immune responses induced by OVA- loaded IMHCSs. IMHCSs are safer adjuvants than QuilA. Our study revealed that pure IMHCSs without further functionalization can be used as a safe adjuvant for promoting Th2-biased immune responses for vaccine delivery.展开更多
Long-lasting protective immune responses are expected following vaccination.However,most vaccines alone are inability to evoke an efficient protection.The combinatory administration of adjuvants with vaccines is criti...Long-lasting protective immune responses are expected following vaccination.However,most vaccines alone are inability to evoke an efficient protection.The combinatory administration of adjuvants with vaccines is critical for generating the enhanced immune responses.Herein,with biocompatible poly(4-vinylpyridine)(P4VP)as template,2.5 nm iron/molybdenum oxide cluster,{Mo_(72)Fe_(30)},is applied as an adjuvant to co-assemble with antigens of Mycobacterium bovis via hydrogen bonding at molecular scale.Molecular scale integration of the antigens and{Mo_(72)Fe_(30)}and their full exposure to body fluid media contribute to the augmentation of both humoral and cellular immune responses of the vaccines after inoculation in mice.Anti-inflammatory factor IL-10 gradually increases after 2 weeks followed by a final back to normal level by the 5th week.The balance between proinflammatory cytokines and anti-inflammatory factors suggests that immune system can be activated in the early stage of infection by the antigens carried by the supra-particles and secrete acute inflammatory factors for host defense and anti-inflammatory factors for immune protection.展开更多
AIM:To study the immunological protective effect of H pylori vaccine with chitosan as an adjuvant and its mechanism.METHODS:Female BALB/c mice were randomly divided into seven groups and orally immunized respectively ...AIM:To study the immunological protective effect of H pylori vaccine with chitosan as an adjuvant and its mechanism.METHODS:Female BALB/c mice were randomly divided into seven groups and orally immunized respectively with PBS,chitosan solution,chitosan particles,H pylori antigen,H pylori antigen plus cholera toxin(CT),H pylori antigen plus chitosan solution,H pylori antigen plus chitosan particles once a week for four weeks.Four weeks after the last immunization,the mice were challenged twice by alive H pylori(1 × 109 CFU/mL)and sacrificed.Part of the gastric mucosa was embedded in paraffin,cut into sections and assayed with Giemsa staining.Part of the gastric mucosa was used to quantitatively culture H pylori.ELISA was used to detect cytokine level in gastric mucosa and anti-H pylori IgG1,IgG2a levels in serum.RESULTS:In the groups with chitosan as an adjuvant,immunological protection was achieved in 60% mice,which was significantly higher than in groups with H pylori antigen alone and without H pylori antigen(P < 0.05 or 0.001).Before challenge,the level of IFN and IL-12 in gastric mucosa was significantly higher in the groups with chitosan as an adjuvant than in the control group and the group without adjuvant(P < 0.05 or 0.005).After challenge,the level of IFN and IL-12 was significantly higher in the groups with adjuvant than in the groups without adjuvant and antigen(P < 0.05 or 0.001).Before challenge,the level of IL-2 in gastric mucosa was not different among different groups.Afterchallenge the level of IL-2 was significantly higher in the groups with adjuvant than in the control group(P < 0.05 or 0.001).Before challenge,the level of IL-10 in gastric mucosa was significantly higher in the groups with chitosan as an adjuvant than in other groups without adjuvant(P < 0.05 or 0.01).After challenge,the level of IL-10 was not different among different groups.Before challenge,the level of IL-4 in gastric mucosa was significantly higher in the groups with chitosan as an adjuvant than in other groups without adjuvant(P < 0.05).After challenge,the level of IL-4 was significantly higher in the groups with chitosan particles as an adjuvant than in the group with CT as an adjuvant(P < 0.05),and in the group with chitosan solution as an adjuvant,the level of IL-4 was significantly higher than that in control group,non-adjuvant group and the groups with CT(P < 0.05 or 0.001).The ratio of anti-H pylori IgG2a/IgG1 in serum was significantly lower in the groups with chitosan as an adjuvant than in the groups with CT as an adjuvant or without adjuvant(P < 0.01).CONCLUSION:H pylori vaccine with chitosan as an adjuvant can protect against H pylori infection and induce both Th1 and Th2 type immune response.展开更多
Infection with hepatitis B virus(HBV) poses a major health threat worldwide, where the magnitude and overburden of chronic carrier state approaches 150 million chronic carriers. The prevalence of HBV is greater among ...Infection with hepatitis B virus(HBV) poses a major health threat worldwide, where the magnitude and overburden of chronic carrier state approaches 150 million chronic carriers. The prevalence of HBV is greater among dialyzed patients compared to the general population owing to their increased vulnerability to blood and its products, along with hazards posed by contaminated hemodialysis tools and devices. Anelectronic systematic search of the published literature was carried and data on the immunological riposte to hepatitis B vaccination among hemodialysis patients was extracted from relevant studies. End stage renal disease patients on hemodialysis have a lower or an absolutely negative riposte to HBV vaccine. Several means have been tried to improve this response with some success, nevertheless none have been universally adopted. Genetic investigations are foreseen to make a break through concerning HBV vaccination.展开更多
To enhance anti-amyloid-beta （Aβ） antibody generation and induce a Th2 immune response, we constructed a new DNA vaccine p（Aβ3-10 ）10-C3d-p28.3 encoding ten repeats of Aβ3-10 and three copies of C3d-p28 as a mo...To enhance anti-amyloid-beta （Aβ） antibody generation and induce a Th2 immune response, we constructed a new DNA vaccine p（Aβ3-10 ）10-C3d-p28.3 encoding ten repeats of Aβ3-10 and three copies of C3d-p28 as a molecular adjuvant. In this study, we administered this adjuvant intramus-cularly to female C57BL/6J mice at 8-10 weeks of age. Enzyme linked immunosorbent assay was used to detect the titer of serum anti-Aβ antibody, isotypes, and cytokines in splenic T cel s. A 3-（4,5-cimethylthiazol-2-yl）-2,5-diphenyl tetrazolium bromide assay was used to detect the prolifera-tion rate of splenic T cel s. Brain sections from a 12-month-old APP/PS1 transgenic mouse were used for detecting the binding capacities of anti-Aβ antibodies to Aβ plaques. The p（Aβ3-10）10-C3d-p28.3 vaccine induced high titers of anti-amyloid-βantibodies, which bound to Aβplaques in APP/PS1 transgenic mouse brain tissue, demonstrating that the vaccine is effective against plaques in a mouse model of Alzheimer’s disease. Moreover, the vaccine elicited a pre-dominantly IgG1 humoral response and low levels of interferon-γ in ex vivo cultured splenocytes, indicating that the vaccine could shift the cel ular immune response towards a Th2 phenotype. This indicated that the vaccine did not elicit a detrimental immune response and had a favorable safety profile. Our results indicate that the p（Aβ3-10）10-C3d-p28.3 vaccine is a promising immunothera-peutic option for Aβvaccination in Alzheimer’s disease.展开更多
Objective： To determine the adjuvant potential of artemisinin with a soluble leishmanial antigen in vaccinating BALB/c mice. Methods： Seventy two female BALB/c mice were randomly assigned into six groups. The mice w...Objective： To determine the adjuvant potential of artemisinin with a soluble leishmanial antigen in vaccinating BALB/c mice. Methods： Seventy two female BALB/c mice were randomly assigned into six groups. The mice were vaccinated with soluble Leishmania antigens （SLA） alone, artemisinin co-administered with SLA, SLA and Bacille Calmette Gu fin （BCG） vaccine, and artemisinin and BCG alone. Unvaccinated mice formed the control group. The induction of cell-mediated immunity following vaccination was determined by measuring in vitro lymphocyte proliferation and the production of interleukin （IL）-4, IL-5 and gamma interferon （IFN-γ） determined by flow cytometry. Protection against L. major was determined by quantifying parasite burdens in L. major infected footpads using a limiting dilution assay and by measuring lesion sizes of the infected footpad compared to the contralateral uninfected footpad. Results： Mice receiving SLA plus artemisinin produced significantly high levels of IL-4 and IL-5 （P 〈 0.05） and low levels of IFN-γ, resulting in exacerbated disease. In addition, subcutaneous administration of SLA ＋ artemisinin, artemisinin alone or SLA alone resulted in the development of large footpad swellings and high parasite loads that were comparable to those of the control unvaccinated mice （P 〉 0.05）, resulting in exacerbated disease. Conclusion： These data suggest that artemisinin is not a suitable adjuvant for Leishmania vaccines. However, since artemisinin has been shown to be effective against Leishmania parasites in vitro and in vivo, further studies ought to be conducted to determine its immunochemotherapeutic potential when co-administered with Leishmania antigens.展开更多
为深入研究羊口疮疫苗诱导机体产生免疫效应的分子机理,用羊口疮疫苗免疫兔,并对其血清中的特异性抗体水平和外周血免疫相关细胞因子的表达水平进行研究。将500 m L灭活的羊口疮病毒感染细胞毒液和经超声波破碎的灭活羊口疮病毒感染细...为深入研究羊口疮疫苗诱导机体产生免疫效应的分子机理,用羊口疮疫苗免疫兔,并对其血清中的特异性抗体水平和外周血免疫相关细胞因子的表达水平进行研究。将500 m L灭活的羊口疮病毒感染细胞毒液和经超声波破碎的灭活羊口疮病毒感染细胞毒液分别浓缩至100 m L,按照佐剂说明书比例,分别与弗氏佐剂、201VG、1313VG、GEL01、11R VG混匀。另外,取灭活的羊口疮痂皮毒液10 m L与201 VG混匀,制备成疫苗。用所制备的不同佐剂疫苗各免疫2只兔子。在免疫后不同时间采集外周血,应用琼脂免疫扩散方法检测血清中特异性抗体效价,同时应用实时荧光定量PCR方法检测外周血中细胞因子表达水平。结果显示:在兔子接种羊口疮疫苗后期,血清中抗体效价除了"1313VG+未破碎病毒"组为1:8之外,其他组别的抗体效价均达到1:16或1:32;各组别外周血中Th1型细胞因子(IL-2、IFN-γ、TNF-α)的表达量与对照组相比总体上升,而Th2型细胞因子(IL-4、IL-6)的表达量总体呈下降趋势。结果表明,羊口疮疫苗可以同时诱导机体产生细胞免疫应答和体液免疫应答,但对该两种免疫应答的诱导水平不同。展开更多
文摘Over the last decade, there has been a flurry of research on adjuvants for vaccines, and several novel adjuvants are now licensed products or in late stage clinical development. The success of adjuvants in enhancing the immune response to antigens has led many researchers to re-focus their vaccine development programs. Although several vaccine candidates have been tested against leishmaniasis, there is yet no effective vaccine against this parasitic disease. Recent research has documented that efforts to develop effective Leishmania vaccine have been limited due to lack of an appropriate adjuvant. In view of this, this review paper outlines some of the adjuvants that have been used in Leishmania vaccine candidates and cites a few of the responses obtained from these studies. The aim of the present review is to consolidate these findings to facilitate the application of these adjuvants in general and experimental vaccinology.
文摘Porcine reproductive and respiratory syndrome (PRRS) is a devastating disease caused by the PRRS virus. The MontanideTM class of flexible polymeric adjuvants has recently been shown to enhance protective immunity against PRRSV infection in piglets when used in combination with PRRS modified live vaccines (MLV). In this study, we explored the efficacy and immunological mechanisms of protection of MontanideTM Gel01 ST (Gel01) adjuvanted modified live PRRSV vaccine in pigs challenged with two genetically distinct strains of PRRSV. Gel01-MLV reduced lymph node pathology scores in pigs challenged with VR-2332 (parental strain of MLV vaccine) but not that in pigs challenged with MN184A (heterologous strain), when compared to that in pigs vaccinated with un-adjuvanted MLV. Pigs vaccinated with Gel01-MLV had higher levels of PRRS-specific antibodies, as measured by IDEXX ELISA and virus neutralizing antibodies, after vaccination and VR-2332 challenge. In addition, pigs vaccinated with Gel01-MLV had decreased levels of IFN-γ, IL-10, and T-regulatory lymphocytes in the blood as compared to that in pigs vaccinated with MLV alone. Interestingly, we found that addition of Gel01 did not change the profile of other T lymphocyte populations after PRRSV challenge. These results demonstrate that the MLV adjuvanted with Gel01 provides enhanced protection against homologous PRRSV infection, possibly by regulating the production of PRRSV-specific antibodies and cytokines involved in the development of T-regulatory cells. Thus, Gel01 ST is a promising adjuvant that can be formulated with PRRSV MLV vaccines to reduce disease severity and tissue damage caused by PRRSV infection in pigs.
文摘Interleukine-2(IL-2) is a growth factor for antigen-stimulated T lymphocytes and is responsible for ~T-cell clonal expansion after antigen recognition. It has been demonstrated that DNA vaccine-elicited immune responses in mice could be augmented substantially by using either an IL-2 protein or a plasmid expressing ~IL-2. Twenty mice, divided into four experimental groups, were immunized with: (1) sham plasmid; ^(2) HIV-1 DNA vaccine alone; (3) HIV-1 DNA vaccine and IL-2 protein; or (4) HIV-1 DNA vaccine and IL-2 plasmid, separately. All the groups were immunized 3 times at a 2-week interval. Fourteen days after the last DNA vaccine injection, recombinant MVA was injected into all the mice except those in group 1. ELISA and ELISPOT were employed to investigate the effect of IL-2 on DNA vaccine immune responses. The obtained results strongly indicate that the efficacy of HIV vaccine can be enhanced by co-administration of a plasmid encoding IL-2.
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Leishmaniasis is a disease that ranges in severity infection. Resistance to infection is associated with from skin lesions to serious disfigurement and fatal systemic a T-helper-1 immune response that activates macrophages to kill the intracellular parasite in a nitric oxide-dependent manner. Conversely, disease progression is generally associated with a T-helper-2 response that activates humoral immunity. Current control is based on chemothera- peutic treatments which are expensive, toxic and associated with high relapse and resistance rates. Vaccination remains the best hope for control of all forms of the disease, and the development of a safe, effective and affordable antileishmanial vaccine is a critical global public-health priority. Extensive evidence from studies in animal models indicates that solid protection can be achieved by immunization with defined subunit vaccines or live-at- tenuated strains of Leishmania. However, to date, no vaccine is available despite substantial efforts by many laboratories. Major impediments in Leishmania vaccine development include： lack of adequate funding from national and international agencies, problems related to the translation of data from animal models to human disease, and the transition from the laboratory to the field. Furthermore, a thorough understanding of protective immune responses and generation and maintenance of the immunological memory, an important but least-studied aspect of antiparasitic vaccine development, during Leishmania infection is needed. This review focuses on the progress of the search for an effective vaccine against human and canine leishmaniasis.
文摘The development of a safe and effective adjuvant that amplifies the immune response to an antigen is important for vaccine delivery. In this study, we developed pristine mesoporous carbon hollow spheres as high-capacity vaccine protein nanocarriers and safe adjuvants for boosting the immune response. Mono-dispersed invaginated mesostructured hollow carbon spheres （IMHCSs） have an average particle size of -200 nm, large pore size of 15 rim, and high pore volume of 2.85 cmB.g-1. IMHCSs exhibited a very high loading capacity （1,040 ~tg-mg-1） towards ovalbumin （OVA, a model antigen）, controlled OVA release behavior, excellent safety profile to normal cells, and high antigen delivery efficacy towards macrophages. In vivo immunization studies in mice demonstrated that OVA-loaded IMHCSs induced a 3-fold higher IgG response compared to a traditional adjuvant QuilA used in veterinary vaccine research. OVA delivered by IMHCSs induced a higher IgG1 concentration than IgG2a, indicating a T-helper 2 （Th2）-polarized response. Interferon-y and interleukin-4 concentration analysis revealed both T-helper 1 （Thl） and Th2 immune responses induced by OVA- loaded IMHCSs. IMHCSs are safer adjuvants than QuilA. Our study revealed that pure IMHCSs without further functionalization can be used as a safe adjuvant for promoting Th2-biased immune responses for vaccine delivery.
基金The work was supported financially by the National Natural Science Foundation of China(Nos.22101086,21961142018,and 51873067)the Natural Science Foundation of Guangdong Province(Nos.2021A1515012024 and 2021A1515010271).
文摘Long-lasting protective immune responses are expected following vaccination.However,most vaccines alone are inability to evoke an efficient protection.The combinatory administration of adjuvants with vaccines is critical for generating the enhanced immune responses.Herein,with biocompatible poly(4-vinylpyridine)(P4VP)as template,2.5 nm iron/molybdenum oxide cluster,{Mo_(72)Fe_(30)},is applied as an adjuvant to co-assemble with antigens of Mycobacterium bovis via hydrogen bonding at molecular scale.Molecular scale integration of the antigens and{Mo_(72)Fe_(30)}and their full exposure to body fluid media contribute to the augmentation of both humoral and cellular immune responses of the vaccines after inoculation in mice.Anti-inflammatory factor IL-10 gradually increases after 2 weeks followed by a final back to normal level by the 5th week.The balance between proinflammatory cytokines and anti-inflammatory factors suggests that immune system can be activated in the early stage of infection by the antigens carried by the supra-particles and secrete acute inflammatory factors for host defense and anti-inflammatory factors for immune protection.
基金Supported by Natural Science Foundation of Jiangxi Province (No.30460052)Program of Jiangxi Provincial Leaders in Their Chosen Field of Learning,No. K010501
文摘AIM:To study the immunological protective effect of H pylori vaccine with chitosan as an adjuvant and its mechanism.METHODS:Female BALB/c mice were randomly divided into seven groups and orally immunized respectively with PBS,chitosan solution,chitosan particles,H pylori antigen,H pylori antigen plus cholera toxin(CT),H pylori antigen plus chitosan solution,H pylori antigen plus chitosan particles once a week for four weeks.Four weeks after the last immunization,the mice were challenged twice by alive H pylori(1 × 109 CFU/mL)and sacrificed.Part of the gastric mucosa was embedded in paraffin,cut into sections and assayed with Giemsa staining.Part of the gastric mucosa was used to quantitatively culture H pylori.ELISA was used to detect cytokine level in gastric mucosa and anti-H pylori IgG1,IgG2a levels in serum.RESULTS:In the groups with chitosan as an adjuvant,immunological protection was achieved in 60% mice,which was significantly higher than in groups with H pylori antigen alone and without H pylori antigen(P < 0.05 or 0.001).Before challenge,the level of IFN and IL-12 in gastric mucosa was significantly higher in the groups with chitosan as an adjuvant than in the control group and the group without adjuvant(P < 0.05 or 0.005).After challenge,the level of IFN and IL-12 was significantly higher in the groups with adjuvant than in the groups without adjuvant and antigen(P < 0.05 or 0.001).Before challenge,the level of IL-2 in gastric mucosa was not different among different groups.Afterchallenge the level of IL-2 was significantly higher in the groups with adjuvant than in the control group(P < 0.05 or 0.001).Before challenge,the level of IL-10 in gastric mucosa was significantly higher in the groups with chitosan as an adjuvant than in other groups without adjuvant(P < 0.05 or 0.01).After challenge,the level of IL-10 was not different among different groups.Before challenge,the level of IL-4 in gastric mucosa was significantly higher in the groups with chitosan as an adjuvant than in other groups without adjuvant(P < 0.05).After challenge,the level of IL-4 was significantly higher in the groups with chitosan particles as an adjuvant than in the group with CT as an adjuvant(P < 0.05),and in the group with chitosan solution as an adjuvant,the level of IL-4 was significantly higher than that in control group,non-adjuvant group and the groups with CT(P < 0.05 or 0.001).The ratio of anti-H pylori IgG2a/IgG1 in serum was significantly lower in the groups with chitosan as an adjuvant than in the groups with CT as an adjuvant or without adjuvant(P < 0.01).CONCLUSION:H pylori vaccine with chitosan as an adjuvant can protect against H pylori infection and induce both Th1 and Th2 type immune response.
文摘Infection with hepatitis B virus(HBV) poses a major health threat worldwide, where the magnitude and overburden of chronic carrier state approaches 150 million chronic carriers. The prevalence of HBV is greater among dialyzed patients compared to the general population owing to their increased vulnerability to blood and its products, along with hazards posed by contaminated hemodialysis tools and devices. Anelectronic systematic search of the published literature was carried and data on the immunological riposte to hepatitis B vaccination among hemodialysis patients was extracted from relevant studies. End stage renal disease patients on hemodialysis have a lower or an absolutely negative riposte to HBV vaccine. Several means have been tried to improve this response with some success, nevertheless none have been universally adopted. Genetic investigations are foreseen to make a break through concerning HBV vaccination.
基金supported by the National Natural Science Foundation of China,No.30471927
文摘To enhance anti-amyloid-beta （Aβ） antibody generation and induce a Th2 immune response, we constructed a new DNA vaccine p（Aβ3-10 ）10-C3d-p28.3 encoding ten repeats of Aβ3-10 and three copies of C3d-p28 as a molecular adjuvant. In this study, we administered this adjuvant intramus-cularly to female C57BL/6J mice at 8-10 weeks of age. Enzyme linked immunosorbent assay was used to detect the titer of serum anti-Aβ antibody, isotypes, and cytokines in splenic T cel s. A 3-（4,5-cimethylthiazol-2-yl）-2,5-diphenyl tetrazolium bromide assay was used to detect the prolifera-tion rate of splenic T cel s. Brain sections from a 12-month-old APP/PS1 transgenic mouse were used for detecting the binding capacities of anti-Aβ antibodies to Aβ plaques. The p（Aβ3-10）10-C3d-p28.3 vaccine induced high titers of anti-amyloid-βantibodies, which bound to Aβplaques in APP/PS1 transgenic mouse brain tissue, demonstrating that the vaccine is effective against plaques in a mouse model of Alzheimer’s disease. Moreover, the vaccine elicited a pre-dominantly IgG1 humoral response and low levels of interferon-γ in ex vivo cultured splenocytes, indicating that the vaccine could shift the cel ular immune response towards a Th2 phenotype. This indicated that the vaccine did not elicit a detrimental immune response and had a favorable safety profile. Our results indicate that the p（Aβ3-10）10-C3d-p28.3 vaccine is a promising immunothera-peutic option for Aβvaccination in Alzheimer’s disease.
文摘Objective： To determine the adjuvant potential of artemisinin with a soluble leishmanial antigen in vaccinating BALB/c mice. Methods： Seventy two female BALB/c mice were randomly assigned into six groups. The mice were vaccinated with soluble Leishmania antigens （SLA） alone, artemisinin co-administered with SLA, SLA and Bacille Calmette Gu fin （BCG） vaccine, and artemisinin and BCG alone. Unvaccinated mice formed the control group. The induction of cell-mediated immunity following vaccination was determined by measuring in vitro lymphocyte proliferation and the production of interleukin （IL）-4, IL-5 and gamma interferon （IFN-γ） determined by flow cytometry. Protection against L. major was determined by quantifying parasite burdens in L. major infected footpads using a limiting dilution assay and by measuring lesion sizes of the infected footpad compared to the contralateral uninfected footpad. Results： Mice receiving SLA plus artemisinin produced significantly high levels of IL-4 and IL-5 （P 〈 0.05） and low levels of IFN-γ, resulting in exacerbated disease. In addition, subcutaneous administration of SLA ＋ artemisinin, artemisinin alone or SLA alone resulted in the development of large footpad swellings and high parasite loads that were comparable to those of the control unvaccinated mice （P 〉 0.05）, resulting in exacerbated disease. Conclusion： These data suggest that artemisinin is not a suitable adjuvant for Leishmania vaccines. However, since artemisinin has been shown to be effective against Leishmania parasites in vitro and in vivo, further studies ought to be conducted to determine its immunochemotherapeutic potential when co-administered with Leishmania antigens.
文摘为深入研究羊口疮疫苗诱导机体产生免疫效应的分子机理,用羊口疮疫苗免疫兔,并对其血清中的特异性抗体水平和外周血免疫相关细胞因子的表达水平进行研究。将500 m L灭活的羊口疮病毒感染细胞毒液和经超声波破碎的灭活羊口疮病毒感染细胞毒液分别浓缩至100 m L,按照佐剂说明书比例,分别与弗氏佐剂、201VG、1313VG、GEL01、11R VG混匀。另外,取灭活的羊口疮痂皮毒液10 m L与201 VG混匀,制备成疫苗。用所制备的不同佐剂疫苗各免疫2只兔子。在免疫后不同时间采集外周血,应用琼脂免疫扩散方法检测血清中特异性抗体效价,同时应用实时荧光定量PCR方法检测外周血中细胞因子表达水平。结果显示:在兔子接种羊口疮疫苗后期,血清中抗体效价除了"1313VG+未破碎病毒"组为1:8之外,其他组别的抗体效价均达到1:16或1:32;各组别外周血中Th1型细胞因子(IL-2、IFN-γ、TNF-α)的表达量与对照组相比总体上升,而Th2型细胞因子(IL-4、IL-6)的表达量总体呈下降趋势。结果表明,羊口疮疫苗可以同时诱导机体产生细胞免疫应答和体液免疫应答,但对该两种免疫应答的诱导水平不同。
