The World Health Organization has declared the rapidly spreading coronavirus to be a global pandemic.The FDA is yet to approve a vaccine for human novel coronavirus.Here,we developed a peptide-based vaccine and used h...The World Health Organization has declared the rapidly spreading coronavirus to be a global pandemic.The FDA is yet to approve a vaccine for human novel coronavirus.Here,we developed a peptide-based vaccine and used high-throughput screening by molecular dynamics simulation to identify T-cell-and p-cell-recognized epitopes for producing specific antibod-ies against SARS-nCoV-2.We construct~12 P'antigenic epitope peptides to develop a more effective vaccine and identify specific antibodies.These epitope peptides selectively presented the best antigen presentation scores for both human pMHC class I and II alleles to develop a strong binding affinity.All antigens identified of SARS-nCoV-2 different proteins by each attached specific~1-7 L linker adaptor were used to construct a broad single peripheral peptide vaccine.It is expected to be highly antigenic with a minimum allergic effect.As a result of these exciting outcomes,expressing a vaccine using the intimated peptide was highly promising and positive to be highly proposed as epitope-based peptide vaccine of specific antibody against SARS-nCoV-2 by initiating T cells and β-cells.An in vitro study for the proposed peptide-based vaccine is.mostly recommended.Further clinical trials are required to check the efficacy of this vaccine.展开更多
Anti-human epidermal growth factor receptor-2 (HER2) immunization can be elicited by vaccination with DNA encoding the extra- or intra-cellular domain (ECD or ICD) of HER2, naked or encap-sulated in viral vectors. HER...Anti-human epidermal growth factor receptor-2 (HER2) immunization can be elicited by vaccination with DNA encoding the extra- or intra-cellular domain (ECD or ICD) of HER2, naked or encap-sulated in viral vectors. HER2-peptides derived from ECD or ICD of HER2, and HER2-pulsed dendritic cells (DCs) or engineered DCs expressing HER2, respectively. We performed a computer- based literature search which includes but is not limited to the following keywords: breast cancer, immunotherapy, HER2-peptide vaccine, HER2-DNA vaccine, HER-DC vaccine, HER2 vaccine, and HER2/neu, in PubMed, Medline, EMBO and Google Scholar;data from recently reported clinical trials were also included. Drawing upon this synthesis of literature, this work summarizes the de-velopment and current trend in experimental and clinical investigations in HER2-positive breast cancer using HER2-specific vaccine and immunotherapy, focusing especially on: (i) DNA-;(ii) peptide-;and (iii) DC-based vaccines. It addresses interventions that have been applied to overcome immunotolerance thereby to improve treatment outcomes. These include blocking the inhibitory cytotoxic T lymphocyte-associated protein-4 (CTLA-4), which is expressed at high levels by regulatory T (Treg) cells, or complete Treg depletion to improve T-cell activation. Moreover, modulatory interventions can provide further improvement in the efficacy of HER2-specific vaccine. The interventions include the use of immunogenic adjuvants such as cytokines interleukin-12 (IL-12), tumor necrosis factor (TNF)-α and granulocyte-macrophage colony-stimulating factor (GM-CSF), the use of Toll-like receptor (TLR) ligands and tetanus toxin’s universal epitopes such as the CD4+ help T (Th)-epitope P30, and the use of either chimeric or heterogenous xenogeneic HER2. Combining active HER2-vaccination with adoptive trastuzumab antibody immunotherapy is likely to increase the effectiveness of each approach alone. The development of effective HER2-vaccines for breast cancer remains a critical challenge. Though these novel interventions seem promising, further investigation is still needed since the results are preliminary. Furthermore, the review discusses the challenges and future perspectives in HER2-vaccine research and development.展开更多
Background NR2B containing N-methyI-D-aspartate （NMDA） receptor plays an important role in the facilitation and maintenance of neuropathic pain. The discrete distribution of NR2B subunit in the central nervous syst...Background NR2B containing N-methyI-D-aspartate （NMDA） receptor plays an important role in the facilitation and maintenance of neuropathic pain. The discrete distribution of NR2B subunit in the central nervous system （CNS） may support reduced side effects of agents that act selectively at this site. Therefore, we investigated the hypothesis that a humoral autoimmune response targeting the NR2B subunit of NMDA receptor relieves pain like behaviours produced by peripheral injury. Methods Rats were immunized subcutaneously with NR2B-Keyhole Limpet Hemocyanin （NR2B-KLH） three times at two-week intervals. NR2B specific IgG titres in sera and cerebrospinal fluid were determined by indirect ELISA. Seven days after the third immunization, 2 of the 3 terminal branches of the sciatic nerve （tibial and common peroneal nerves） were tightly ligated. Behavioural testing was carried out on every other day after surgery, until 7 days after surgery. The lumbar spinal cord （L4-6） was removed on day 7 after ligation. The expression of NR2B protein in the lumbar spinal cord was determined using Western blotting. Results After the second vaccination, NR2B specific IgG in sera was detected to be 〉0.5 μg/ml in six of nine rats. After the third vaccination, all the immunized rats had 〉2.2 μg/ml. Titres of NR2B specific IgG in sera peaked 42 days post initial immunization and persisted for over 70 days. No NR2B specific IgG was detected in sera from PBS or KLH group. The behavioural thresholds in NR2B group were significantly higher than those in PBS and KLH groups on day 7 after ligation. NR2B specific IgG in CSF in NR2B group could not be detected on day 1 before spinal dissection; but could be detected on day 7 after surgery. The expression of NR2B protein in group NR2B was significantly lower than in PBS and KLH groups on day 7 after surgery. Conclusion The NR2B peptide could be used as a vaccine against neuropathic pain, which could be associated with reduction of NR2B protein in the lumbar spinal cord.展开更多
Newcastle disease virus(NDV)and H9N2 subtype Avian influenza virus(AIV)are two notorious avian respiratory pathogens that cause great losses in the poultry industry.Current inactivated commercial vaccines against NDV ...Newcastle disease virus(NDV)and H9N2 subtype Avian influenza virus(AIV)are two notorious avian respiratory pathogens that cause great losses in the poultry industry.Current inactivated commercial vaccines against NDV and AIV have the disadvantages of inadequate mucosal responses,while an attenuated live vaccine bears the risk of mutation.Dendritic cell(DC)targeting strategies are attractive for their potent mucosal and adaptive immune-stimulating ability against respiratory pathogens.In this study,DC-binding peptide(DCpep)-decorated chimeric virus-like particles(cVLPs),containing NDV haemagglutinin–neuraminidase(HN)and AIV haemagglutinin(HA),were developed as a DC-targeting mucosal vaccine candidate.DCpep-decorated cVLPs activated DCs in vitro,and induced potent immune stimulation in chickens,with enhanced secretory immunoglobulin A(sIgA)secretion and splenic T cell differentiation.40μg cVLPs can provide full protection against the challenge with homologous,heterologous NDV strains,and AIV H9N2.In addition,DCpep-decorated cVLPs could induce a better immune response when administered intranasally than intramuscularly,as indicated by robust s IgA secretion and a reduced virus shedding period.Taken together,this chimericVLPs are a promising vaccine candidate to control NDV and AIV H9N2 and a useful platform bearing multivalent antigens.展开更多
季节性流感疫苗需每年接种,且保护型别有限,因此需研发一种针对多种毒株的通用流感疫苗。国外已研发出基于流感病毒血凝素(hemagglutinin,HA)茎部、基质蛋白2(matrix protein 2,M2)离子通道的胞外域(M2e)、多部位重组蛋白及合成多肽的...季节性流感疫苗需每年接种,且保护型别有限,因此需研发一种针对多种毒株的通用流感疫苗。国外已研发出基于流感病毒血凝素(hemagglutinin,HA)茎部、基质蛋白2(matrix protein 2,M2)离子通道的胞外域(M2e)、多部位重组蛋白及合成多肽的通用疫苗,且在动物实验及早期临床试验中显示出较好的安全性及免疫原性,但目前均尚未批准上市。本文就不同病毒靶点的通用流感疫苗的研究进展作一综述,为进一步的研发提供理论依据。展开更多
文摘The World Health Organization has declared the rapidly spreading coronavirus to be a global pandemic.The FDA is yet to approve a vaccine for human novel coronavirus.Here,we developed a peptide-based vaccine and used high-throughput screening by molecular dynamics simulation to identify T-cell-and p-cell-recognized epitopes for producing specific antibod-ies against SARS-nCoV-2.We construct~12 P'antigenic epitope peptides to develop a more effective vaccine and identify specific antibodies.These epitope peptides selectively presented the best antigen presentation scores for both human pMHC class I and II alleles to develop a strong binding affinity.All antigens identified of SARS-nCoV-2 different proteins by each attached specific~1-7 L linker adaptor were used to construct a broad single peripheral peptide vaccine.It is expected to be highly antigenic with a minimum allergic effect.As a result of these exciting outcomes,expressing a vaccine using the intimated peptide was highly promising and positive to be highly proposed as epitope-based peptide vaccine of specific antibody against SARS-nCoV-2 by initiating T cells and β-cells.An in vitro study for the proposed peptide-based vaccine is.mostly recommended.Further clinical trials are required to check the efficacy of this vaccine.
文摘Anti-human epidermal growth factor receptor-2 (HER2) immunization can be elicited by vaccination with DNA encoding the extra- or intra-cellular domain (ECD or ICD) of HER2, naked or encap-sulated in viral vectors. HER2-peptides derived from ECD or ICD of HER2, and HER2-pulsed dendritic cells (DCs) or engineered DCs expressing HER2, respectively. We performed a computer- based literature search which includes but is not limited to the following keywords: breast cancer, immunotherapy, HER2-peptide vaccine, HER2-DNA vaccine, HER-DC vaccine, HER2 vaccine, and HER2/neu, in PubMed, Medline, EMBO and Google Scholar;data from recently reported clinical trials were also included. Drawing upon this synthesis of literature, this work summarizes the de-velopment and current trend in experimental and clinical investigations in HER2-positive breast cancer using HER2-specific vaccine and immunotherapy, focusing especially on: (i) DNA-;(ii) peptide-;and (iii) DC-based vaccines. It addresses interventions that have been applied to overcome immunotolerance thereby to improve treatment outcomes. These include blocking the inhibitory cytotoxic T lymphocyte-associated protein-4 (CTLA-4), which is expressed at high levels by regulatory T (Treg) cells, or complete Treg depletion to improve T-cell activation. Moreover, modulatory interventions can provide further improvement in the efficacy of HER2-specific vaccine. The interventions include the use of immunogenic adjuvants such as cytokines interleukin-12 (IL-12), tumor necrosis factor (TNF)-α and granulocyte-macrophage colony-stimulating factor (GM-CSF), the use of Toll-like receptor (TLR) ligands and tetanus toxin’s universal epitopes such as the CD4+ help T (Th)-epitope P30, and the use of either chimeric or heterogenous xenogeneic HER2. Combining active HER2-vaccination with adoptive trastuzumab antibody immunotherapy is likely to increase the effectiveness of each approach alone. The development of effective HER2-vaccines for breast cancer remains a critical challenge. Though these novel interventions seem promising, further investigation is still needed since the results are preliminary. Furthermore, the review discusses the challenges and future perspectives in HER2-vaccine research and development.
基金the National Natural Science Foundation of China(No.30471660)
文摘Background NR2B containing N-methyI-D-aspartate （NMDA） receptor plays an important role in the facilitation and maintenance of neuropathic pain. The discrete distribution of NR2B subunit in the central nervous system （CNS） may support reduced side effects of agents that act selectively at this site. Therefore, we investigated the hypothesis that a humoral autoimmune response targeting the NR2B subunit of NMDA receptor relieves pain like behaviours produced by peripheral injury. Methods Rats were immunized subcutaneously with NR2B-Keyhole Limpet Hemocyanin （NR2B-KLH） three times at two-week intervals. NR2B specific IgG titres in sera and cerebrospinal fluid were determined by indirect ELISA. Seven days after the third immunization, 2 of the 3 terminal branches of the sciatic nerve （tibial and common peroneal nerves） were tightly ligated. Behavioural testing was carried out on every other day after surgery, until 7 days after surgery. The lumbar spinal cord （L4-6） was removed on day 7 after ligation. The expression of NR2B protein in the lumbar spinal cord was determined using Western blotting. Results After the second vaccination, NR2B specific IgG in sera was detected to be 〉0.5 μg/ml in six of nine rats. After the third vaccination, all the immunized rats had 〉2.2 μg/ml. Titres of NR2B specific IgG in sera peaked 42 days post initial immunization and persisted for over 70 days. No NR2B specific IgG was detected in sera from PBS or KLH group. The behavioural thresholds in NR2B group were significantly higher than those in PBS and KLH groups on day 7 after ligation. NR2B specific IgG in CSF in NR2B group could not be detected on day 1 before spinal dissection; but could be detected on day 7 after surgery. The expression of NR2B protein in group NR2B was significantly lower than in PBS and KLH groups on day 7 after surgery. Conclusion The NR2B peptide could be used as a vaccine against neuropathic pain, which could be associated with reduction of NR2B protein in the lumbar spinal cord.
基金supported by grants from the National Key Research and Development Program of China(Grant No.2018YFD0500100)the National Natural Science Foundation of China(Grant Nos.31772735,31472195)+2 种基金the Jiangsu Provincial Natural Science Foundation of China(Grant No.BK20180299)Jiangsu Agriculture Science and Technology Innovation Fund CX(19)3019the Key Technology Research and Development Project of Jilin Province(Grant No.20180201021NY)。
文摘Newcastle disease virus(NDV)and H9N2 subtype Avian influenza virus(AIV)are two notorious avian respiratory pathogens that cause great losses in the poultry industry.Current inactivated commercial vaccines against NDV and AIV have the disadvantages of inadequate mucosal responses,while an attenuated live vaccine bears the risk of mutation.Dendritic cell(DC)targeting strategies are attractive for their potent mucosal and adaptive immune-stimulating ability against respiratory pathogens.In this study,DC-binding peptide(DCpep)-decorated chimeric virus-like particles(cVLPs),containing NDV haemagglutinin–neuraminidase(HN)and AIV haemagglutinin(HA),were developed as a DC-targeting mucosal vaccine candidate.DCpep-decorated cVLPs activated DCs in vitro,and induced potent immune stimulation in chickens,with enhanced secretory immunoglobulin A(sIgA)secretion and splenic T cell differentiation.40μg cVLPs can provide full protection against the challenge with homologous,heterologous NDV strains,and AIV H9N2.In addition,DCpep-decorated cVLPs could induce a better immune response when administered intranasally than intramuscularly,as indicated by robust s IgA secretion and a reduced virus shedding period.Taken together,this chimericVLPs are a promising vaccine candidate to control NDV and AIV H9N2 and a useful platform bearing multivalent antigens.
文摘季节性流感疫苗需每年接种,且保护型别有限,因此需研发一种针对多种毒株的通用流感疫苗。国外已研发出基于流感病毒血凝素(hemagglutinin,HA)茎部、基质蛋白2(matrix protein 2,M2)离子通道的胞外域(M2e)、多部位重组蛋白及合成多肽的通用疫苗,且在动物实验及早期临床试验中显示出较好的安全性及免疫原性,但目前均尚未批准上市。本文就不同病毒靶点的通用流感疫苗的研究进展作一综述,为进一步的研发提供理论依据。
