Directory of Open Access Journals (Sweden)
Spyros A Kalams
Full Text Available DNA vaccines are a promising approach to vaccination since they circumvent the problem of vector-induced immunity. DNA plasmid cytokine adjuvants have been shown to augment immune responses in small animals and in macaques.We performed two first in human HIV vaccine trials in the US, Brazil and Thailand of an RNA-optimized truncated HIV-1 gag gene (p37 DNA derived from strain HXB2 administered either alone or in combination with dose-escalation of IL-12 or IL-15 plasmid cytokine adjuvants. Vaccinations with both the HIV immunogen and cytokine adjuvant were generally well-tolerated and no significant vaccine-related adverse events were identified. A small number of subjects developed asymptomatic low titer antibodies to IL-12 or IL-15. Cellular immunogenicity following 3 and 4 vaccinations was poor, with response rates to gag of 4.9%/8.7% among vaccinees receiving gag DNA alone, 0%/11.5% among those receiving gag DNA+IL-15, and no responders among those receiving DNA+high dose (1500 ug IL-12 DNA. However, after three doses, 44.4% (4/9 of vaccinees receiving gag DNA and intermediate dose (500 ug of IL-12 DNA demonstrated a detectable cellular immune response.This combination of HIV gag DNA with plasmid cytokine adjuvants was well tolerated. There were minimal responses to HIV gag DNA alone, and no apparent augmentation with either IL-12 or IL-15 plasmid cytokine adjuvants. Despite the promise of DNA vaccines, newer formulations or methods of delivery will be required to increase their immunogenicity.Clinicaltrials.gov NCT00115960 NCT00111605.
Directory of Open Access Journals (Sweden)
Matthias Tenbusch
Full Text Available BACKGROUND: Targeting antigens encoded by DNA vaccines to dendritic cells (DCs in the presence of adjuvants enhances their immunogenicity and efficacy in mice. METHODOLOGY/PRINCIPAL FINDINGS: To explore the immunogenicity of this approach in non-human primates, we generated a single chain antibody to the antigen uptake receptor DEC-205 expressed on rhesus macaque DCs. DNA vaccines encoding this single chain antibody fused to the SIV capsid protein were delivered to six monkeys each by either intramuscular electroporation or conventional intramuscular injection co-injected or not with poly ICLC, a stabilized poly I: C analogue, as adjuvant. Antibodies to capsid were induced by the DC-targeting and non-targeting control DNA delivered by electroporation while conventional DNA immunization at a 10-fold higher dose of DNA failed to induce detectable humoral immune responses. Substantial cellular immune responses were also observed after DNA electroporation of both DNAs, but stronger responses were induced by the non-targeting vaccine. Conventional immunization with the DC-targeting DNA at a 10-fold higher dose did not give rise to substantial cellular immune responses, neither when co-injected with poly ICLC. CONCLUSIONS/SIGNIFICANCE: The study confirms the potent immunogenicity of DNA vaccines delivered by electroporation. Targeting the DNA via a single chain antibody to DEC-205 expressed by DCs, however, does not improve the immunogenicity of the antigens in non-human primates.
Immunogenicity of an HPV-16 L2 DNA vaccine
Hitzeroth, Inga I.; Passmore, Jo-Ann S.; Shephard, Enid; Stewart, Debbie; Müller, Martin; Williamson, Anna-Lise; Rybicki, Edward P.; Kast, W. Martin
2009-01-01
The ability to elicit cross-neutralizing antibodies makes human papillomavirus (HPV) L2 capsid protein a possible HPV vaccine. We examined and compared the humoral response of mice immunised with a HPV-16 L2 DNA vaccine or with HPV-16 L2 protein. The L2 DNA vaccine elicited a non-neutralising antibody response unlike the L2 protein. L2 DNA vaccination suppressed the growth of L2-expressing C3 tumor cells, which is a T cell mediated effect, demonstrating that the lack of non-neutralizing antibody induction by L2 DNA was not caused by lack of T cell immunogenicity of the construct. PMID:19559114
Directory of Open Access Journals (Sweden)
Eric S Rosenberg
2010-05-01
Full Text Available An effective therapeutic vaccine that could augment immune control of HIV-1 replication may abrogate or delay the need for antiretroviral therapy. AIDS Clinical Trials Group (ACTG A5187 was a phase I/II, randomized, placebo-controlled, double-blinded trial to evaluate the safety and immunogenicity of an HIV-1 DNA vaccine (VRC-HVDNA 009-00-VP in subjects treated with antiretroviral therapy during acute/early HIV-1 infection. (clinicaltrials.gov NCT00125099Twenty healthy HIV-1 infected subjects who were treated with antiretroviral therapy during acute/early HIV-1 infection and had HIV-1 RNA<50 copies/mL were randomized to receive either vaccine or placebo. The objectives of this study were to evaluate the safety and immunogenicity of the vaccine. Following vaccination, subjects interrupted antiretroviral treatment, and set-point HIV-1 viral loads and CD4 T cell counts were determined 17-23 weeks after treatment discontinuation.Twenty subjects received all scheduled vaccinations and discontinued antiretroviral therapy at week 30. No subject met a primary safety endpoint. No evidence of differences in immunogenicity were detected in subjects receiving vaccine versus placebo. There were also no significant differences in set-point HIV-1 viral loads or CD4 T cell counts following treatment discontinuation. Median set-point HIV-1 viral loads after treatment discontinuation in vaccine and placebo recipients were 3.5 and 3.7 log(10 HIV-1 RNA copies/mL, respectively.The HIV-1 DNA vaccine (VRC-HIVDNA 009-00-VP was safe but poorly immunogenic in subjects treated with antiretroviral therapy during acute/early HIV-1 infection. Viral set-points were similar between vaccine and placebo recipients following treatment interruption. However, median viral load set-points in both groups were lower than in historical controls, suggesting a possible role for antiretroviral therapy in persons with acute or early HIV-1 infection and supporting the safety of
DEFF Research Database (Denmark)
Birkelund, Svend; Mygind, P; Holm, A
1996-01-01
this protein. By use of recombinant DNA techniques, we located the epitopes for two MAbs in the C-terminal variable part. Although the antibodies reacted in an immunoblot assay, it was not possible to map the epitopes completely by use of 16-mer synthetic peptides displaced by one amino acid corresponding......Chlamydia trachomatis DnaK is an important immunogen in chlamydial infections. DnaK is composed of a conserved N-terminal ATP-binding domain and a variable C-terminal peptide-binding domain. To locate the immunogenic part of C. trachomatis Dnak, we generated monoclonal antibodies (MAbs) against...... with the two antibodies. The epitopes were found not to overlap. To obtain DnaK fragments recognized by the antibodies with the same affinity as native C. trachomatis DnaK, it was necessary to express, respectively, regions of 127 and 77 amino acids. The MAbs described in this study thus recognized...
Zhang, Yonghong; Liang, Shuang; Li, Xiujin; Wang, Liyue; Zhang, Jianlou; Xu, Jian; Huo, Shanshan; Cao, Xuebin; Zhong, Zhenyu; Zhong, Fei
2015-07-09
Our previous study showed that IL-2 and IL-7 could mutually enhance the immunogenicity of canine parvovirus VP2 DNA vaccine, although the underlying mechanism remained unknown. Here, we used the OVA gene as a DNA vaccine in a mouse model to test their enhancement on DNA vaccine immunogenicity and to explore the molecular mechanism. Results showed that both IL-2 and IL-7 genes significantly increased the immunogenicity of OVA DNA vaccine in mice. Co-administration of IL-2 and IL-7 genes with OVA DNA significantly increased OVA-specific antibody titers, T cell proliferation and IFN-γ production compared with IL-2 or IL-7 alone, confirming that IL-2 and IL-7 mutually enhanced DNA vaccine immunogenicity. Mechanistically, we have shown that IL-2 significantly stimulated generation of IL-7 receptor-expressing lymphocytes, and that IL-7 significantly induced IL-2 receptor expression. These results contribute to an explanation of the mechanism of the mutual effects of IL-2 and IL-7 on enhancing DNA vaccine immunogenicity and provided a basis for further investigation on their mutual effects on adjuvant activity and immune regulation. Copyright © 2015 Elsevier Ltd. All rights reserved.
Borthwick, Nicola J; Lane, Thirusha; Moyo, Nathifa; Crook, Alison; Shim, Jung Min; Baines, Ian; Wee, Edmund G; Hawkins, Philip N; Gillmore, Julian D; Hanke, Tomáš; Pepys, Mark B
2018-01-01
The failure of DNA vaccination in humans, in contrast to its efficacy in some species, is unexplained. Observational and interventional experimental evidence suggests that DNA immunogenicity may be prevented by binding of human serum amyloid P component (SAP). SAP is the single normal DNA binding protein in human plasma. The drug (R)-1-[6-[(R)-2-carboxypyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC, miridesap), developed for treatment of systemic amyloidosis and Alzheimer's disease, depletes circulating SAP by 95-99%. The proof-of-concept HIV-CORE 003 clinical trial tested whether SAP depletion by CPHPC would enhance the immune response in human volunteers to DNA vaccination delivering the HIVconsv immunogen derived from conserved sub-protein regions of HIV-1. Human volunteers received 3 intramuscular immunizations with an experimental DNA vaccine (DDD) expressing HIV-1-derived immunogen HIVconsv, with or without prior depletion of SAP by CPHPC. All subjects were subsequently boosted by simian (chimpanzee) adenovirus (C)- and poxvirus MVA (M)-vectored vaccines delivering the same immunogen. After administration of each vaccine modality, the peak total magnitudes, kinetics, functionality and memory subsets of the T-cell responses to HIVconsv were thoroughly characterized. No differences were observed between the CPHPC treated and control groups in any of the multiple quantitative and qualitative parameters of the T-cell responses to HIVconsv, except that after SAP depletion, there was a statistically significantly greater breadth of T-cell specificities, that is the number of recognized epitopes, following the DDDC vaccination. The protocol used here for SAP depletion by CPHPC prior to DNA vaccination produced only a very modest suggestion of enhanced immunogenicity. Further studies will be required to determine whether SAP depletion might have a practical value in DNA vaccination for other plasmid backbones and/or immunogens. Clinicaltrials
Kim, Yeu-Chun; Song, Jae-Min; Lipatov, Aleksandr S.; Choi, Seong-O; Lee, Jeong Woo; Donis, Ruben O.; Compans, Richard W.; Kang, Sang-Moo; Prausnitz, Mark R.
2012-01-01
Effective public health responses to an influenza pandemic require an effective vaccine that can be manufactured and administered to large populations in the shortest possible time. In this study, we evaluated a method for vaccination against avian influenza virus that uses a DNA vaccine for rapid manufacturing and delivered by a microneedle skin patch for simplified administration and increased immunogenicity. We prepared patches containing 700 µm-long microneedles coated with an avian H5 influenza hemagglutinin DNA vaccine from A/Viet Nam/1203/04 influenza virus. The coating DNA dose increased with DNA concentration in the coating solution and the number of dip coating cycles. Coated DNA was released into the skin tissue by dissolution within minutes. Vaccination of mice using microneedles induced higher levels of antibody responses and hemagglutination inhibition titers, and improved protection against lethal infection with avian influenza as compared to conventional intramuscular delivery of the same dose of the DNA vaccine. Additional analysis showed that the microneedle coating solution containing carboxymethylcellulose and a surfactant may have negatively affected the immunogenicity of the DNA vaccine. Overall, this study shows that DNA vaccine delivery by microneedles can be a promising approach for improved vaccination to mitigate an influenza pandemic. PMID:22504442
Directory of Open Access Journals (Sweden)
Ros Chapman
Full Text Available In an effort to make affordable vaccines suitable for the regions most affected by HIV-1, we have constructed stable vaccines that express an HIV-1 subtype C mosaic Gag immunogen (BCG-GagM, MVA-GagM and DNA-GagM. Mosaic immunogens have been designed to address the tremendous diversity of this virus. Here we have shown that GagM buds from cells infected and transfected with MVA-GagM and DNA-GagM respectively and forms virus-like particles. Previously we showed that a BCG-GagM prime MVA-GagM boost generated strong cellular immune responses in mice. In this study immune responses to the DNA-GagM and MVA-GagM vaccines were evaluated in homologous and heterologous prime-boost vaccinations. The DNA homologous prime boost vaccination elicited predominantly CD8+ T cells while the homologous MVA vaccination induced predominantly CD4+ T cells. A heterologous DNA-GagM prime MVA-GagM boost induced strong, more balanced Gag CD8+ and CD4+ T cell responses and that were predominantly of an effector memory phenotype. The immunogenicity of the mosaic Gag (GagM was compared to a naturally occurring subtype C Gag (GagN using a DNA homologous vaccination regimen. DNA-GagN expresses a natural Gag with a sequence that was closest to the consensus sequence of subtype C viruses sampled in South Africa. DNA-GagM homologous vaccination induced cumulative HIV-1 Gag-specific IFN-γ ELISPOT responses that were 6.5-fold higher than those induced by the DNA-GagN vaccination. Similarly, DNA-GagM vaccination generated 7-fold higher levels of cytokine-positive CD8+ T cells than DNA-GagN, indicating that this subtype C mosaic Gag elicits far more potent immune responses than a consensus-type Gag. Cells transfected and infected with DNA-GagM and MVA-GagM respectively, expressed high levels of GagM and produced budding virus-like particles. Our data indicates that a heterologous prime boost regimen using DNA and MVA vaccines expressing HIV-1 subtype C mosaic Gag is highly
Directory of Open Access Journals (Sweden)
Sandhya Vasan
Full Text Available DNA-based vaccines have been safe but weakly immunogenic in humans to date.We sought to determine the safety, tolerability, and immunogenicity of ADVAX, a multigenic HIV-1 DNA vaccine candidate, injected intramuscularly by in vivo electroporation (EP in a Phase-1, double-blind, randomized placebo-controlled trial in healthy volunteers. Eight volunteers each received 0.2 mg, 1 mg, or 4 mg ADVAX or saline placebo via EP, or 4 mg ADVAX via standard intramuscular injection at weeks 0 and 8. A third vaccination was administered to eleven volunteers at week 36. EP was safe, well-tolerated and considered acceptable for a prophylactic vaccine. EP delivery of ADVAX increased the magnitude of HIV-1-specific cell mediated immunity by up to 70-fold over IM injection, as measured by gamma interferon ELISpot. The number of antigens to which the response was detected improved with EP and increasing dosage. Intracellular cytokine staining analysis of ELISpot responders revealed both CD4+ and CD8+ T cell responses, with co-secretion of multiple cytokines.This is the first demonstration in healthy volunteers that EP is safe, tolerable, and effective in improving the magnitude, breadth and durability of cellular immune responses to a DNA vaccine candidate.ClinicalTrials.gov NCT00545987.
Knudsen, Maria L; Mbewe-Mvula, Alice; Rosario, Maximillian; Johansson, Daniel X; Kakoulidou, Maria; Bridgeman, Anne; Reyes-Sandoval, Arturo; Nicosia, Alfredo; Ljungberg, Karl; Hanke, Tomás; Liljeström, Peter
2012-04-01
Vaccination using "naked" DNA is a highly attractive strategy for induction of pathogen-specific immune responses; however, it has been only weakly immunogenic in humans. Previously, we constructed DNA-launched Semliki Forest virus replicons (DREP), which stimulate pattern recognition receptors and induce augmented immune responses. Also, in vivo electroporation was shown to enhance immune responses induced by conventional DNA vaccines. Here, we combine these two approaches and show that in vivo electroporation increases CD8(+) T cell responses induced by DREP and consequently decreases the DNA dose required to induce a response. The vaccines used in this study encode the multiclade HIV-1 T cell immunogen HIVconsv, which is currently being evaluated in clinical trials. Using intradermal delivery followed by electroporation, the DREP.HIVconsv DNA dose could be reduced to as low as 3.2 ng to elicit frequencies of HIV-1-specific CD8(+) T cells comparable to those induced by 1 μg of a conventional pTH.HIVconsv DNA vaccine, representing a 625-fold molar reduction in dose. Responses induced by both DREP.HIVconsv and pTH.HIVconsv were further increased by heterologous vaccine boosts employing modified vaccinia virus Ankara MVA.HIVconsv and attenuated chimpanzee adenovirus ChAdV63.HIVconsv. Using the same HIVconsv vaccines, the mouse observations were supported by an at least 20-fold-lower dose of DNA vaccine in rhesus macaques. These data point toward a strategy for overcoming the low immunogenicity of DNA vaccines in humans and strongly support further development of the DREP vaccine platform for clinical evaluation.
Histone deacetylase inhibitors augment doxorubicin-induced DNA damage in cardiomyocytes.
Ververis, Katherine; Rodd, Annabelle L; Tang, Michelle M; El-Osta, Assam; Karagiannis, Tom C
2011-12-01
Histone deacetylase inhibitors have emerged as a new class of anticancer therapeutics with suberoylanilide hydroxamic acid (Vorinostat) and depsipeptide (Romidepsin) already being approved for clinical use. Numerous studies have identified that histone deacetylase inhibitors will be most effective in the clinic when used in combination with conventional cancer therapies such as ionizing radiation and chemotherapeutic agents. One promising combination, particularly for hematologic malignancies, involves the use of histone deacetylase inhibitors with the anthracycline, doxorubicin. However, we previously identified that trichostatin A can potentiate doxorubicin-induced hypertrophy, the dose-limiting side-effect of the anthracycline, in cardiac myocytes. Here we have the extended the earlier studies and evaluated the effects of combinations of the histone deacetylase inhibitors, trichostatin A, valproic acid and sodium butyrate on doxorubicin-induced DNA double-strand breaks in cardiomyocytes. Using γH2AX as a molecular marker for the DNA lesions, we identified that all of the broad-spectrum histone deacetylase inhibitors tested augment doxorubicin-induced DNA damage. Furthermore, it is evident from the fluorescence photomicrographs of stained nuclei that the histone deacetylase inhibitors also augment doxorubicin-induced hypertrophy. These observations highlight the importance of investigating potential side-effects, in relevant model systems, which may be associated with emerging combination therapies for cancer.
Koh, Yi T.; Gray, Andrew; Higgins, Sean A.; Hubby, Bolyn; Kast, W. Martin
2009-01-01
Background Androgen ablation (AA) causes apoptosis of normal and neoplastic prostate cells. It is a standard treatment for advanced prostate cancer. Androgen ablation-mediated immunological effects include bone marrow hyperplasia, thymic regeneration, T and B cell lymphopoeisis and restoration of age-related peripheral T cell dysfunction. Androgens also regulate the transcription of several cytokines. Dendritic cells (DC) are the most potent antigen presenting cells that can activate antigen-specific naïve T cells. Despite myriad clinical trials involving DC-based prostate cancer immunotherapies, the effects of AA on DC function remain largely uncharacterized. Therefore, we investigated the effects of AA on DC and whether it could improve the efficacy of prostate cancer immunotherapy. Methods Cytokine expression changes due to AA were quantified by multiplex ELISA. Flow cytometry was used to assess AA-mediated effects on DC maturation and expression of costimulatory markers. Mixed leukocyte reactions and cell-mediated lysis assays elucidated the role of androgens in DC function. The effect of AA on the efficacy of vaccination against a prostate tumor-associated antigen was tested using Elispot assays. Results Androgen ablation increased dendritic cell maturation and costimulatory marker expression, but had no effect on DC costimulatory function. However, DC isolated from castrated mice increased the expression of key cytokines by antigen-experienced T cells while decreasing their expression in naïve cells. Finally, androgen ablation improved immune responses to vaccination only when applied after immunization. Conclusion Androgen ablation causes differential effects of DC on primary and secondary T cell responses, thus augmenting vaccine immunogenicity only when applied after immunization. PMID:19143030
C3d enhanced DNA vaccination induced humoral immune response to glycoprotein C of pseudorabies virus
International Nuclear Information System (INIS)
Tong Tiezhu; Fan Huiying; Tan Yadi; Xiao Shaobo; Ling Jieyu; Chen Huanchun; Guo Aizhen
2006-01-01
Murine C3d were utilized to enhance immunogenicity of pseudorabies virus (PrV) gC DNA vaccination. Three copies of C3d and four copies of CR2-binding domain M28 4 were fused, respectively, to truncated gC gene encoding soluble glycoprotein C (sgC) in pcDNA3.1. BALB/c mice were, respectively, immunized with recombinant plasmids, blank vector, and inactivated vaccine. The antibody ELISA titer for sgC-C3d 3 DNA was 49-fold more than that for sgC DNA, and the neutralizing antibody obtained 8-fold rise. Protection of mice from death after lethal PrV (316 LD 5 ) challenge was augmented from 25% to 100%. Furthermore, C3d fusion increased Th2-biased immune response by inducing IL-4 production. The IL-4 level for sgC-C3d 3 DNA immunization approached that for the inactivated vaccine. Compared to C3d, M28 enhanced sgC DNA immunogenicity to a lesser extent. In conclusion, we demonstrated that murine C3d fusion significantly enhanced gC DNA immunity by directing Th1-biased to a balanced and more effective Th1/Th2 response
International Nuclear Information System (INIS)
Kim, Seung Jo; Suh, Dongchul; Park, Sang Eun; Park, Jeong-Sook; Byun, Hyang-Min; Lee, Chan; Lee, Sun Young; Kim, Inho; Oh, Yu-Kyoung
2003-01-01
To increase the potency of DNA vaccines, we constructed genetic fusion vaccines encoding antigen, secretion signal, and/or chemokine RANTES. The DNA vaccines encoding secreted hepatitis B surface antigen (HBsAg) were constructed by inserting HBsAg gene into an expression vector with an endoplasmic reticulum (ER)-targeting secretory signal sequence. The plasmid encoding secretory HBsAg (pER/HBs) was fused to cDNA of RANTES, generating pER/HBs/R. For comparison, HBsAg genes were cloned into pVAX1 vector with no signal sequence (pHBs), and further linked to the N-terminus of RANTES (pHBs/R). Immunofluorescence study showed the cytoplasmic localization of HBsAg protein expressed from pHBs and pHBs/R, but not from pER/HBs and pER/HBs/R at 48 h after transfection. In mice, RANTES-fused DNA vaccines more effectively elicited the levels of HBsAg-specific IgG antibodies than pHBs. All the DNA vaccines induced higher levels of IgG 2a rather than IgG 1 antibodies. Of RANTES-fused vaccines, pER/HBs/R encoding the secreted fusion protein revealed much higher humoral and CD8 + T cell-stimulating responses compared to pHBs/R. These results suggest that the immunogenicity of DNA vaccines could be enhanced by genetic fusion to a secretory signal peptide sequence and RANTES
DEFF Research Database (Denmark)
Holst, Peter Johannes; Bassi, Maria Rosaria; Thomsen, Allan Randrup
2010-01-01
DNA vaccines are versatile and safe, but limited immunogenicity has prevented their use in the clinical setting. Experimentally, immunogenicity may be enhanced by the use of new delivery technologies, by coadministration of cytokines and pathogen-associated molecular patterns, or by fusion...... of antigens into molecular domains that enhance antigen presentation. More specifically, the immunogenicity of DNA vaccines may benefit from increased protein synthesis, increased T-cell help and MHC class I presentation, and the addition of a range of specific cytokines and pathogen-associated molecular...... with viral-vectored vaccines, various synergistic components may need to be incorporated into DNA vaccines. From the perspective of the future clinical use of DNA vaccines, it has been suggested that antigen presentation should be improved and cytokine coadministration attempted. However, even...
Juan, Long; Xiao, Zhao; Song, Yun; Zhijian, Zhang; Jing, Jin; Kun, Yu; Yuna, Hao; Dongfa, Dai; Lili, Ding; Liuxin, Tan; Fei, Liang; Nan, Liu; Fang, Yuan; Yuying, Sun; Yongzhi, Xi
2015-01-01
Current clinically available treatments for rheumatoid arthritis (RA) fail to cure the disease or unsatisfactorily halt disease progression. To overcome these limitations, the development of therapeutic DNA vaccines and boosters may offer new promising strategies. Because type II collagen (CII) as a critical autoantigen in RA and native chicken type II collagen (nCCII) has been used to effectively treat RA, we previously developed a novel therapeutic DNA vaccine encoding CCII (pcDNA-CCOL2A1) with efficacy comparable to that of the current "gold standard", methotrexate(MTX). Here, we systemically evaluated the safety and immunogenicity of the pcDNA-CCOL2A1 vaccine in normal Wistar rats. Group 1 received only a single intramuscular injection into the hind leg with pcDNA-CCOL2A1 at the maximum dosage of 3 mg/kg on day 0; Group 2 was injected with normal saline (NS) as a negative control. All rats were monitored daily for any systemic adverse events, reactions at the injection site, and changes in body weights. Plasma and tissues from all experimental rats were collected on day 14 for routine examinations of hematology and biochemistry parameters, anti-CII IgG antibody reactivity, and histopathology. Our results indicated clearly that at the maximum dosage of 3 mg/kg, the pcDNA-CCOL2A1 vaccine was safe and well-tolerated. No abnormal clinical signs or deaths occurred in the pcDNA-CCOL2A1 group compared with the NS group. Furthermore, no major alterations were observed in hematology, biochemistry, and histopathology, even at the maximum dose. In particularly, no anti-CII IgG antibodies were detected in vaccinated normal rats at 14 d after vaccination; this was relevant because we previously demonstrated that the pcDNA-CCOL2A1 vaccine, when administered at the therapeutic dosage of 300 μg/kg alone, did not induce anti-CII IgG antibody production and significantly reduced levels of anti-CII IgG antibodies in the plasma of rats with established collagen-induced arthritis
Kim, Tae S; Jung, Mi Y; Cho, Daeho; Cohen, Edward P
2006-10-30
Breast cancer cells, like other types of neoplastic cells, form weakly immunogenic tumor-associated antigens. The antigenic properties of the tumor-associated antigens can be enhanced if they are expressed by highly immunogenic cells. In this study, a cancer vaccine was prepared by transfer of a cDNA expression library from SB5b breast carcinoma into mouse fibroblast cells of C3H/He mouse origin (H-2(k)), that had been previously modified to secrete GM-CSF and to express allogeneic class I-determinants (H-2(b)). The transfected syngeneic/allogeneic fibroblasts secreting GM-CSF were used as a vaccine in C3H/He mice. Robust cell-mediated immunity toward the breast cancer cells was generated in mice immunized with the cDNA-based vaccine. The immunity, mediated predominantly by CD8(+) T lymphocytes, was directed toward the breast cancer cells, but not against either of two other non-cross-reactive neoplasms of C3H/He mice. The immunity was sufficient to prolong the survival of mice with established breast cancer. Among other advantages, preparation of the vaccine by cDNA-transfer into a fibroblast cell line enabled the recipient cells to be modified in advance of DNA-transfer to augment their immunogenic properties. As the transferred DNA is replicated as the transfected cells divide, the vaccine could be prepared from microgram quantities of tumor tissue.
Immunogenicity of autoantigens
Directory of Open Access Journals (Sweden)
Keller Andreas
2011-07-01
Full Text Available Abstract Background Autoantibodies against self-antigens have been associated not only with autoimmune diseases, but also with cancer and are even found in healthy individuals. The mechanism causing the autoantibody response remains elusive for the majority of the immunogenic antigens. To deepen the understanding of autoantibody responses, we ask whether natural-occurring, autoimmunity-associated and tumor-associated antigens have structural or biological features related to the immune response. To this end, we have carried out the most comprehensive in-silicio study of different groups of autoantigens including large antigen sets identified by our groups combined with publicly available antigen sets. Results We found evidence for an enrichment of genes with a larger exon length increasing the probability of the occurrence of potential immunogenic features such as mutations, SNPs, immunogenic sequence patterns and structural epitopes, or alternative splicing events. While SNPs seem to play a more central role in autoimmunity, somatic mutations seem to be stronger enriched in tumor-associated antigens. In addition, antigens of autoimmune diseases are different from other antigen sets in that they appear preferentially secreted, have frequently an extracellular location, and they are enriched in pathways associated with the immune system. Furthermore, for autoantibodies in general, we found enrichment of sequence-based properties including coiled-coils motifs, ELR motifs, and Zinc finger DNA-binding motifs. Moreover, we found enrichment of proteins binding to proteins or nucleic acids including RNA and enrichment of proteins that are part of ribosome or spliceosome. Both, homologies to proteins of other species and an enrichment of ancient protein domains indicate that immunogenic proteins are evolutionary conserved and that mimicry might play a central role. Conclusions Our results provide evidence that proteins which i are evolutionary conserved
The future of human DNA vaccines.
Li, Lei; Saade, Fadi; Petrovsky, Nikolai
2012-12-31
DNA vaccines have evolved greatly over the last 20 years since their invention, but have yet to become a competitive alternative to conventional protein or carbohydrate based human vaccines. Whilst safety concerns were an initial barrier, the Achilles heel of DNA vaccines remains their poor immunogenicity when compared to protein vaccines. A wide variety of strategies have been developed to optimize DNA vaccine immunogenicity, including codon optimization, genetic adjuvants, electroporation and sophisticated prime-boost regimens, with each of these methods having its advantages and limitations. Whilst each of these methods has contributed to incremental improvements in DNA vaccine efficacy, more is still needed if human DNA vaccines are to succeed commercially. This review foresees a final breakthrough in human DNA vaccines will come from application of the latest cutting-edge technologies, including "epigenetics" and "omics" approaches, alongside traditional techniques to improve immunogenicity such as adjuvants and electroporation, thereby overcoming the current limitations of DNA vaccines in humans. Copyright © 2012 Elsevier B.V. All rights reserved.
Directory of Open Access Journals (Sweden)
Peter T Loudon
2010-06-01
Full Text Available The recent H5N1 avian and H1N1 swine-origin influenza virus outbreaks reaffirm that the threat of a world-wide influenza pandemic is both real and ever-present. Vaccination is still considered the best strategy for protection against influenza virus infection but a significant challenge is to identify new vaccine approaches that offer accelerated production, broader protection against drifted and shifted strains, and the capacity to elicit anti-viral immune responses in the respiratory tract at the site of viral entry. As a safe alternative to live attenuated vaccines, the mucosal and systemic immunogenicity of an H1N1 influenza (A/New Caledonia/20/99 HA DNA vaccine administered by particle-mediated epidermal delivery (PMED or gene gun was analyzed in rhesus macaques.Macaques were immunized at weeks 0, 8, and 16 using a disposable single-shot particle-mediated delivery device designed for clinical use that delivers plasmid DNA directly into cells of the epidermis. Significant levels of hemagglutination inhibiting (HI antibodies and cytokine-secreting HA-specific T cells were observed in the periphery of macaques following 1-3 doses of the PMED HA DNA vaccine. In addition, HA DNA vaccination induced detectable levels of HA-specific mucosal antibodies and T cells in the lung and gut-associated lymphoid tissues of vaccinated macaques. Importantly, co-delivery of a DNA encoding the rhesus macaque GM-CSF gene was found to significantly enhance both the systemic and mucosal immunogenicity of the HA DNA vaccine.These results provide strong support for the development of a particle-mediated epidermal DNA vaccine for protection against respiratory pathogens such as influenza and demonstrate, for the first time, the ability of skin-delivered GM-CSF to serve as an effective mucosal adjuvant for vaccine induction of immune responses in the gut and respiratory tract.
Akt Kinase-Mediated Checkpoint of cGAS DNA Sensing Pathway
Directory of Open Access Journals (Sweden)
Gil Ju Seo
2015-10-01
Full Text Available Upon DNA stimulation, cyclic GMP-AMP synthase (cGAS synthesizes the second messenger cyclic GMP-AMP (cGAMP that binds to the STING, triggering antiviral interferon-β (IFN-β production. However, it has remained undetermined how hosts regulate cGAS enzymatic activity after the resolution of DNA immunogen. Here, we show that Akt kinase plays a negative role in cGAS-mediated anti-viral immune response. Akt phosphorylated the S291 or S305 residue of the enzymatic domain of mouse or human cGAS, respectively, and this phosphorylation robustly suppressed its enzymatic activity. Consequently, expression of activated Akt led to the reduction of cGAMP and IFN-β production and the increase of herpes simplex virus 1 replication, whereas treatment with Akt inhibitor augmented cGAS-mediated IFN-β production. Furthermore, expression of the phosphorylation-resistant cGAS S291A mutant enhanced IFN-β production upon DNA stimulation, HSV-1 infection, and vaccinia virus infection. Our study identifies an Akt kinase-mediated checkpoint to fine-tune hosts’ immune responses to DNA stimulation.
Expression and immunogenicity of novel subunit enterovirus 71 VP1 antigens
International Nuclear Information System (INIS)
Xu, Juan; Wang, Shixia; Gan, Weihua; Zhang, Wenhong; Ju, Liwen; Huang, Zuhu; Lu, Shan
2012-01-01
Highlights: ► EV71 is a major emerging infectious disease in many Asian countries. ► Inactivated EV71 vaccines are in clinical studies but their safety and efficacy are unknown. ► Developing subunit based EV71 vaccines is significant and novel antigen design is needed. ► DNA immunization is an efficient tool to test the immunogenicity of VP1 based EV71 vaccines. ► Multiple VP1 antigens are developed showing immunogenic potential. -- Abstract: Hand, foot, and mouth disease (HFMD) is a common viral illness in young children. HFMD is caused by viruses belonging to the enterovirus genus of the picornavirus family. Recently, enterovirus 71 (EV71) has emerged as a virulent agent for HFMD with severe clinical outcomes. In the current report, we conducted a pilot antigen engineering study to optimize the expression and immunogenicity of subunit VP1 antigen for the design of EV71 vaccines. DNA immunization was adopted as a simple technical approach to test different designs of VP1 antigens without the need to express VP1 protein in vitro first. Our studies indicated that the expression and immunogenicity of VP1 protein can be improved with alternated VP1 antigen designs. Data presented in the current report revealed novel pathways to optimize the design of VP1 antigen-based EV71 vaccines.
Directory of Open Access Journals (Sweden)
Smita S. Iyer
2014-02-01
Full Text Available Since the initial proof-of-concept studies examining the ability of antigen-encoded plasmid DNA to serve as an immunogen, DNA vaccines have evolved as a clinically safe and effective platform for priming HIV-specific cellular and humoral responses in heterologous “prime-boost” vaccination regimens. Direct injection of plasmid DNA into the muscle induces T- and B-cell responses against foreign antigens. However, the insufficient magnitude of this response has led to the development of approaches for enhancing the immunogenicity of DNA vaccines. The last two decades have seen significant progress in the DNA-based vaccine platform with optimized plasmid constructs, improved delivery methods, such as electroporation, the use of molecular adjuvants and novel strategies combining DNA with viral vectors and subunit proteins. These innovations are paving the way for the clinical application of DNA-based HIV vaccines. Here, we review preclinical studies on the DNA-prime/modified vaccinia Ankara (MVA-boost vaccine modality for HIV. There is a great deal of interest in enhancing the immunogenicity of DNA by engineering DNA vaccines to co-express immune modulatory adjuvants. Some of these adjuvants have demonstrated encouraging results in preclinical and clinical studies, and these data will be examined, as well.
Deng, Liufu; Liang, Hua; Xu, Meng; Yang, Xuanming; Burnette, Byron; Arina, Ainhoa; Li, Xiao-Dong; Mauceri, Helena; Beckett, Michael; Darga, Thomas; Huang, Xiaona; Gajewski, Thomas F; Chen, Zhijian J; Fu, Yang-Xin; Weichselbaum, Ralph R
2014-11-20
Ionizing radiation-mediated tumor regression depends on type I interferon (IFN) and the adaptive immune response, but several pathways control I IFN induction. Here, we demonstrate that adaptor protein STING, but not MyD88, is required for type I IFN-dependent antitumor effects of radiation. In dendritic cells (DCs), STING was required for IFN-? induction in response to irradiated-tumor cells. The cytosolic DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS) mediated sensing of irradiated-tumor cells in DCs. Moreover, STING was essential for radiation-induced adaptive immune responses, which relied on type I IFN signaling on DCs. Exogenous IFN-? treatment rescued the cross-priming by cGAS or STING-deficient DCs. Accordingly, activation of STING by a second messenger cGAMP administration enhanced antitumor immunity induced by radiation. Thus radiation-mediated antitumor immunity in immunogenic tumors requires a functional cytosolic DNA-sensing pathway and suggests that cGAMP treatment might provide a new strategy to improve radiotherapy. Copyright © 2014 Elsevier Inc. All rights reserved.
Expression and immunogenicity of novel subunit enterovirus 71 VP1 antigens
Energy Technology Data Exchange (ETDEWEB)
Xu, Juan [China-US Vaccine Research Center, The First Affiliated Hospital, Nanjing Medical University (China); Department of Microbiology and Immunology, Nanjing Medical University (China); Wang, Shixia [China-US Vaccine Research Center, The First Affiliated Hospital, Nanjing Medical University (China); Department of Medicine, University of Massachusetts Medical School (United States); Gan, Weihua [Department of Pediatrics, The Second Affiliated Hospital, Nanjing Medical University (China); Zhang, Wenhong [Department of Infectious Diseases, Huashan Hospital, Fudan University (China); Ju, Liwen [School of Public Health, Fudan University (China); Huang, Zuhu [Department of Infectious Diseases, The First Affiliated Hospital, Nanjing Medical University (China); China-US Vaccine Research Center, The First Affiliated Hospital, Nanjing Medical University (China); Lu, Shan, E-mail: shan.lu@umassmed.edu [Department of Infectious Diseases, The First Affiliated Hospital, Nanjing Medical University (China); China-US Vaccine Research Center, The First Affiliated Hospital, Nanjing Medical University (China); Department of Medicine, University of Massachusetts Medical School (United States)
2012-04-20
Highlights: Black-Right-Pointing-Pointer EV71 is a major emerging infectious disease in many Asian countries. Black-Right-Pointing-Pointer Inactivated EV71 vaccines are in clinical studies but their safety and efficacy are unknown. Black-Right-Pointing-Pointer Developing subunit based EV71 vaccines is significant and novel antigen design is needed. Black-Right-Pointing-Pointer DNA immunization is an efficient tool to test the immunogenicity of VP1 based EV71 vaccines. Black-Right-Pointing-Pointer Multiple VP1 antigens are developed showing immunogenic potential. -- Abstract: Hand, foot, and mouth disease (HFMD) is a common viral illness in young children. HFMD is caused by viruses belonging to the enterovirus genus of the picornavirus family. Recently, enterovirus 71 (EV71) has emerged as a virulent agent for HFMD with severe clinical outcomes. In the current report, we conducted a pilot antigen engineering study to optimize the expression and immunogenicity of subunit VP1 antigen for the design of EV71 vaccines. DNA immunization was adopted as a simple technical approach to test different designs of VP1 antigens without the need to express VP1 protein in vitro first. Our studies indicated that the expression and immunogenicity of VP1 protein can be improved with alternated VP1 antigen designs. Data presented in the current report revealed novel pathways to optimize the design of VP1 antigen-based EV71 vaccines.
Jancovich, James K; Chapman, Dave; Hansen, Debra T; Robida, Mark D; Loskutov, Andrey; Craciunescu, Felicia; Borovkov, Alex; Kibler, Karen; Goatley, Lynnette; King, Katherine; Netherton, Christopher L; Taylor, Geraldine; Jacobs, Bertram; Sykes, Kathryn; Dixon, Linda K
2018-04-15
African swine fever virus (ASFV) causes an acute hemorrhagic fever in domestic pigs, with high socioeconomic impact. No vaccine is available, limiting options for control. Although live attenuated ASFV can induce up to 100% protection against lethal challenge, little is known of the antigens which induce this protective response. To identify additional ASFV immunogenic and potentially protective antigens, we cloned 47 viral genes in individual plasmids for gene vaccination and in recombinant vaccinia viruses. These antigens were selected to include proteins with different functions and timing of expression. Pools of up to 22 antigens were delivered by DNA prime and recombinant vaccinia virus boost to groups of pigs. Responses of immune lymphocytes from pigs to individual recombinant proteins and to ASFV were measured by interferon gamma enzyme-linked immunosorbent spot (ELISpot) assays to identify a subset of the antigens that consistently induced the highest responses. All 47 antigens were then delivered to pigs by DNA prime and recombinant vaccinia virus boost, and pigs were challenged with a lethal dose of ASFV isolate Georgia 2007/1. Although pigs developed clinical and pathological signs consistent with acute ASFV, viral genome levels were significantly reduced in blood and several lymph tissues in those pigs immunized with vectors expressing ASFV antigens compared with the levels in control pigs. IMPORTANCE The lack of a vaccine limits the options to control African swine fever. Advances have been made in the development of genetically modified live attenuated ASFV that can induce protection against challenge. However, there may be safety issues relating to the use of these in the field. There is little information about ASFV antigens that can induce a protective immune response against challenge. We carried out a large screen of 30% of ASFV antigens by delivering individual genes in different pools to pigs by DNA immunization prime and recombinant vaccinia
Akt Kinase-Mediated Checkpoint of cGAS DNA Sensing Pathway.
Seo, Gil Ju; Yang, Aerin; Tan, Brandon; Kim, Sungyoon; Liang, Qiming; Choi, Younho; Yuan, Weiming; Feng, Pinghui; Park, Hee-Sung; Jung, Jae U
2015-10-13
Upon DNA stimulation, cyclic GMP-AMP synthase (cGAS) synthesizes the second messenger cyclic GMP-AMP (cGAMP) that binds to the STING, triggering antiviral interferon-β (IFN-β) production. However, it has remained undetermined how hosts regulate cGAS enzymatic activity after the resolution of DNA immunogen. Here, we show that Akt kinase plays a negative role in cGAS-mediated anti-viral immune response. Akt phosphorylated the S291 or S305 residue of the enzymatic domain of mouse or human cGAS, respectively, and this phosphorylation robustly suppressed its enzymatic activity. Consequently, expression of activated Akt led to the reduction of cGAMP and IFN-β production and the increase of herpes simplex virus 1 replication, whereas treatment with Akt inhibitor augmented cGAS-mediated IFN-β production. Furthermore, expression of the phosphorylation-resistant cGAS S291A mutant enhanced IFN-β production upon DNA stimulation, HSV-1 infection, and vaccinia virus infection. Our study identifies an Akt kinase-mediated checkpoint to fine-tune hosts' immune responses to DNA stimulation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Street, Matthew; Thambyah, Ashvin; Dray, Michael; Amirapu, Satya; Tuari, Donna; Callon, Karen E; McIntosh, Julie D; Burkert, Kristina; Dunbar, P Rod; Coleman, Brendan; Cornish, Jillian; Musson, David S
2015-10-20
Rotator cuff tears can cause significant pain and functional impairment. Without surgical repair, the rotator cuff has little healing potential, and following surgical repair, they are highly prone to re-rupture. Augmenting such repairs with a biomaterial scaffold has been suggested as a potential solution. Extracellular matrix (ECM)-based scaffolds are the most commonly used rotator cuff augments, although to date, reports on their success are variable. Here, we utilize pre-clinical in vitro and in vivo assays to assess the efficacy of a novel biomaterial scaffold, ovine forestomach extracellular matrix (OFM), in augmenting rotator cuff repair. OFM was assessed in vitro for primary tenocyte growth and adherence, and for immunogenicity using an assay of primary human dendritic cell activation. In vivo, using a murine model, supraspinatus tendon repairs were carried out in 34 animals. Augmentation with OFM was compared to sham surgery and unaugmented control. At 6- and 12-week time points, the repairs were analysed biomechanically for strength of repair and histologically for quality of healing. OFM supported tenocyte growth in vitro and did not cause an immunogenic response. Augmentation with OFM improved the quality of healing of the repaired tendon, with no evidence of excessive inflammatory response. However, there was no biomechanical advantage of augmentation. The ideal rotator cuff tendon augment has not yet been identified or clinically implemented. ECM scaffolds offer a promising solution to a difficult clinical problem. Here, we have shown improved histological healing with OFM augmentation. Identifying materials that offset the poorer mechanical properties of the rotator cuff post-injury/repair and enhance organised tendon healing will be paramount to incorporating augmentation into surgical treatment of the rotator cuff.
Relapse rate following antithyroid drug therapy of immunogenic and non-immunogenic hyperthyroidism
International Nuclear Information System (INIS)
Voth, E.; Dickmann, N.; Schicha, H.; Emrich, D.
1990-01-01
Data of 196 patients treated for hyperthyroidism exclusively with anthyroid drugs were analyzed retrospectively concerning the relapse rate within a follow-up period of four years. Patients were subdivided for primary or recurrent disease, and for immunogenic or non-immunogenic hyperthyroidism, respectively. In immunogenic as well as in non-immunogenic hyperthyroidism, the relapse rate was significantly lower for patients with primary disease (35% and 52%, respectively) compared to those with recurrent hyperthyroidism (82%, p [de
Safety and Immunogenicity of an Anti-Zika Virus DNA Vaccine - Preliminary Report.
Tebas, Pablo; Roberts, Christine C; Muthumani, Kar; Reuschel, Emma L; Kudchodkar, Sagar B; Zaidi, Faraz I; White, Scott; Khan, Amir S; Racine, Trina; Choi, Hyeree; Boyer, Jean; Park, Young K; Trottier, Sylvie; Remigio, Celine; Krieger, Diane; Spruill, Susan E; Bagarazzi, Mark; Kobinger, Gary P; Weiner, David B; Maslow, Joel N
2017-10-04
Background Although Zika virus (ZIKV) infection is typically self-limiting, other associated complications such as congenital birth defects and the Guillain-Barré syndrome are well described. There are no approved vaccines against ZIKV infection. Methods In this phase 1, open-label clinical trial, we evaluated the safety and immunogenicity of a synthetic, consensus DNA vaccine (GLS-5700) encoding the ZIKV premembrane and envelope proteins in two groups of 20 participants each. The participants received either 1 mg or 2 mg of vaccine intradermally, with each injection followed by electroporation (the use of a pulsed electric field to introduce the DNA sequence into cells) at baseline, 4 weeks, and 12 weeks. Results The median age of the participants was 38 years, and 60% were women; 78% were white, and 22% black; in addition, 30% were Hispanic. At the interim analysis at 14 weeks (i.e., after the third dose of vaccine), no serious adverse events were reported. Local reactions at the vaccination site (e.g., injection-site pain, redness, swelling, and itching) occurred in approximately 50% of the participants. After the third dose of vaccine, binding antibodies (as measured on enzyme-linked immunosorbent assay) were detected in all the participants, with geometric mean titers of 1642 and 2871 in recipients of 1 mg and 2 mg of vaccine, respectively. Neutralizing antibodies developed in 62% of the samples on Vero-cell assay. On neuronal-cell assay, there was 90% inhibition of ZIKV infection in 70% of the serum samples and 50% inhibition in 95% of the samples. The intraperitoneal injection of postvaccination serum protected 103 of 112 IFNAR knockout mice (bred with deletion of genes encoding interferon-α and interferon-β receptors) (92%) that were challenged with a lethal dose of ZIKV-PR209 strain; none of the mice receiving baseline serum survived the challenge. Survival was independent of the neutralization titer. Conclusions In this phase 1, open-label clinical
PD-L1 peptide co-stimulation increases immunogenicity of a dendritic cell-based cancer vaccine
DEFF Research Database (Denmark)
Munir Ahmad, Shamaila; Martinenaite, Evelina; Hansen, Morten
2016-01-01
elicited by the DC vaccine even further. Consequently, we observed a significant increase in the number of vaccine-reacting T cells in vitro. In conclusion, activation of PD-L1-specific T cells may directly modulate immunogenicity of DC vaccines. Addition of PD-L1 epitopes may thus be an easily applicable...... and attractive option to augment the effectiveness of cancer vaccines and other immunotherapeutic agents....
Techniques for augmentation of exogenous DNA uptake by ovine spermatozoa
Hoseini Pajooh, K.; Tajik, P.; Karimipoor, M.; Behdani, M.
2016-01-01
Sperm mediated gene transfer can be an inexpensive and simple method in animal transgenesis; however its efficiency is poor, mainly due to the spermatozoa’s lesser uptake of exogenous DNA. In the present study, the effects of lipofection and other augmentation techniques, such as sperm freezing and spermatozoa treatment with triton X100 and DMSO, on exogenous DNA uptake by sheep spermatozoa and motility of sperms with plasmid uptake were evaluated. In the first experiment, ram sperms were incubated with a complex of rhodamine labeled plasmid (p-EGFP) and Lipofectamine 2000TM. In the second, spermatozoa were treated with Triton X-100TM or DMSO or were frozen without cryoprotectant. The results indicated that there was no significant difference (Plipofected sperms with 300 and 600 ng of plasmid in comparison with control group, i.e. transfected without lipofectamine. Furthermore, lipofection could not improve sperm motility during true plasmid uptake. Almost all of triton X100 treated and frozen-thawed spermatozoa had absorbed foreign DNA, though all were immotile. In spermatozoa treated with 0.1% DMSO, plasmid absorption rate (69.40%) was significantly higher (P<0.05) than untreated spermatozoa (57.80%), but sperm motility was not significantly different from control group. In conclusion, lipofectamine® 2000 could neither improve transfection rate, nor support motility in transfected sperms. The methods inducing membrane disruption like, freeze-thaw and triton X100 treatment, can be used in ICSI-sperm mediated gene transfer without the need for sperm selection, provided that they cause no damage to sperm nucleus. PMID:27656225
Recombinant Brucella abortus gene expressing immunogenic protein
Energy Technology Data Exchange (ETDEWEB)
Mayfield, J.E.; Tabatabai, L.B.
1991-06-11
This patent describes a synthetic recombinant DNA molecule containing a DNA sequence. It comprises a gene of Brucella abortus encoding an immunogenic protein having a molecular weight of approximately 31,000 daltons as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis under denaturing conditions, the protein having an isoelectric point around 4.9, and containing a twenty-five amino acid sequence from its amino terminal end consisting of Gln-Ala-Pro-Thr-Phe-Phe-Arg-Ile-Gly-Thr-Gly-Gly-Thr-Ala-Gly-Thr-Tyr-Tyr-Pro-Ile-Gly-Gly-Leu-Ile-Ala, wherein Gln, Ala, Pro, Thr, Phe, Arg, Ile, Gly, Tyr, and Leu, respectively, represent glutamine, alanine, proline, threonine, phenylalanine, arginine, isolecuine, glycine, tyrosine, and leucine.
Kang, Dae-Woon; Shin, Sung-Chan; Jang, Jeon-Yeob; Park, Hee-Young; Lee, Jin-Choon; Wang, Soo-Geun; Lee, Byung-Joo
2017-01-01
The clinical application of allogenic and/or xenogenic cartilage for vocal fold augmentation requires to remove the antigenic cellular component. The objective of this study was to assess the effect of cartilage decellularization and determine the change in immunogenicity after detergent treatment in human nasal septal cartilage flakes made by the freezing and grinding method. Human nasal septal cartilages were obtained from surgical cases. The harvested cartilages were treated by the freezing and grinding technique. The obtained cartilage flakes were treated with 1% Triton X-100 or 2% sodium dodecyl sulfate (SDS) for decellularization of the cartilage flakes. Hematoxylin and eosin stain (H&E stain), surface electric microscopy, immunohistochemical stain for major histocompatibility complex I and II, and ELISA for DNA contents were performed to assess the effect of cartilage decellularization after detergent treatment. A total of 10 nasal septal cartilages were obtained from surgical cases. After detergent treatment, the average size of the cartilage flakes was significantly decreased. With H&E staining, the cell nuclei of decellularized cartilage flakes were not observed. The expression of major histocompatibility complex (MHC)-I and II antigens was not identified in the decellularized cartilage flakes after treatment with detergent. DNA content was removed almost entirely from the decellularized cartilage flakes. Treatment with 2% SDS or 1% Triton X-100 for 1 hour appears to be a promising method for decellularization of human nasal septal cartilage for vocal fold augmentation. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.
ZIKA-001: Safety and Immunogenicity of an Engineered DNA Vaccine Against ZIKA virus infection
Tebas, Pablo; Roberts, Christine C; Muthumani, Kar; Reuschel, Emma; White, Scott; Khan, Amir S; Racine, Trina; Choi, Hyeree; Zaidi, Faraz; Boyer, Jean; Kudchodkar, Sagar; Park, Young K; Trottier, Sylvie; Remigio, Celine; Krieger, Diane; Kobinger, Gary P; Weiner, David; Maslow, Joel
2017-01-01
Abstract Background While Zika virus (ZIKV) infection is typically self-limited, congenital birth defects and Guillain-Barré syndrome are well-described. There are no therapies or vaccines against ZIKV infection. Methods ZIKA-001 is a phase I, open label, clinical trial designed to evaluate the safety, side effect profile, and immunogenicity of a synthetic, DNA vaccine (GLS-5700) targeting the pre-membrane+envelope proteins (prME) of the virus. Two groups of 20 participants received GLS-5700 at one of two dose levels: 1 mg or 2 mg DNA/dose at 0, 4, and 12 weeks. Vaccine was administered as 0.1 or 0.2 ml (1 or 2 mg) intradermal (ID) injection followed by electroporation (EP) with the CELLECTRA®-3P device Results The median age of the 40 participants was 38 (IQR 30–54) years; 60% were female 30% Latino and 78% white. No SAEs have been reported to date. Local minor AEs were injection site pain, redness, swelling and itching that occurred in half of the participants. Systemic adverse events were rare and included headache, myalgias, upper respiratory infections, fatigue/malaise and nausea. Four weeks after the first dose 25% vs. 60% of the participants in the 1 mg and 2 mg dose seroconverted. By week 6, 2 weeks after the second dose, the response was 65 and 84% respectively and 2 weeks after the third dose all participants in both dosing groups developed antibodies. At the end of the vaccination period over 60% of vaccinated person neutralized Zika virus in a vero cell assay and greater than 80% on neuronal cell targets. The protective efficacy of the antibodies generated by the vaccine was evaluated in the lethal IFNAR−/− mouse model. After the intraperitoneal administration of 0.1 ml of either baseline, week 14 serum or PBS the animals were challenged with 106 PFUs of ZIKV PR209 isolate. Whereas animals administered PBS (control) or baseline serum succumbed after a median of 5 days, those pretreated with week 14 serum from study participants survived
Directory of Open Access Journals (Sweden)
Anna Stachyra
2014-01-01
Full Text Available Highly pathogenic avian influenza viruses (HPAIVs cause huge economic losses in the poultry industry because of high mortality rate in infected flocks and trade restrictions. Protective antibodies, directed mainly against hemagglutinin (HA, are the primary means of protection against influenza outbreaks. A recombinant DNA vaccine based on the sequence of H5 HA from the H5N1/A/swan/Poland/305-135V08/2006 strain of HPAIV was prepared. Sequence manipulation included deletion of the proteolytic cleavage site to improve protein stability, codon usage optimization to improve translation and stability of RNA in host cells, and cloning into a commercially available vector to enable expression in animal cells. Naked plasmid DNA was complexed with a liposomal carrier and the immunization followed the prime–boost strategy. The immunogenic potential of the DNA vaccine was first proved in broilers in near-to-field conditions resembling a commercial farm. Next, the protective activity of the vaccine was confirmed in SPF layer-type chickens. Experimental infections (challenge experiments indicated that 100% of vaccinated chickens were protected against H5N1 of the same clade and that 70% of them were protected against H5N1 influenza virus of a different clade. Moreover, the DNA vaccine significantly limited (or even eliminated transmission of the virus to contact control chickens. Two intramuscular doses of DNA vaccine encoding H5 HA induced a strong protective response in immunized chicken. The effective protection lasted for a minimum 8 weeks after the second dose of the vaccine and was not limited to the homologous H5N1 virus. In addition, the vaccine reduced shedding of the virus.
International Nuclear Information System (INIS)
Ebina, Hirotaka; Kanemura, Yuka; Suzuki, Yasutsugu; Urata, Kozue; Misawa, Naoko; Koyanagi, Yoshio
2012-01-01
HIV-1 possesses a viral protein, integrase (IN), which is necessary for its efficient integration in target cells. However, it has been reported that an IN-defective HIV strain is still capable of integration. Here, we assessed the ability of wild type (WT) HIV-1 to establish infection in the presence of IN inhibitors. We observed a low, yet clear infection of inhibitor-incubated cells infected with WT HIV which was identical to cells infected with IN-deficient HIV, D64A. Furthermore, the IN-independent integration could be enhanced by the pretreatment of cells with DNA-damaging agents suggesting that integration is mediated by a DNA repair system. Moreover, significantly faster viral replication kinetics with augmented viral DNA integration was observed after infection in irradiated cells treated with IN inhibitor compared to nonirradiated cells. Altogether, our results suggest that HIV DNA has integration potential in the presence of an IN inhibitor and may serve as a virus reservoir.
Energy Technology Data Exchange (ETDEWEB)
Ebina, Hirotaka, E-mail: hebina@virus.kyoto-u.ac.jp; Kanemura, Yuka; Suzuki, Yasutsugu; Urata, Kozue; Misawa, Naoko; Koyanagi, Yoshio
2012-05-25
HIV-1 possesses a viral protein, integrase (IN), which is necessary for its efficient integration in target cells. However, it has been reported that an IN-defective HIV strain is still capable of integration. Here, we assessed the ability of wild type (WT) HIV-1 to establish infection in the presence of IN inhibitors. We observed a low, yet clear infection of inhibitor-incubated cells infected with WT HIV which was identical to cells infected with IN-deficient HIV, D64A. Furthermore, the IN-independent integration could be enhanced by the pretreatment of cells with DNA-damaging agents suggesting that integration is mediated by a DNA repair system. Moreover, significantly faster viral replication kinetics with augmented viral DNA integration was observed after infection in irradiated cells treated with IN inhibitor compared to nonirradiated cells. Altogether, our results suggest that HIV DNA has integration potential in the presence of an IN inhibitor and may serve as a virus reservoir.
Directory of Open Access Journals (Sweden)
Adriano R Tonelli
2009-12-01
Full Text Available Adriano R Tonelli1, Farshid Rouhani1, Ning Li2, Pam Schreck1, Mark L Brantly11Alpha-1 Research Program, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, 2Department of Epidemiology and Biostatistics, University of Florida, Gainesville, Florida, USAIntroduction: Intravenous augmentation therapy with purified intravenous alpha-1 antitrypsin replaces the deficient protein and is the only currently approved treatment for alpha-1 antitrypsin deficiency (AATD related lung disease. While augmentation therapy has been available for more than 20 years, there are a limited number of studies evaluating the effect of augmentation on lung function.Material and methods: We examined the decline in forced expiratory volume in one second (FEV1 in patients enrolled in the Alpha-1 Foundation DNA and Tissue Bank in relation to the use or not of alpha-1 antitrypsin augmentation therapy. For the purpose of our analysis we included 164 patients with AATD and PI ZZ genotype.Results: Mean age of the patients was 60 years, 52% were females, 94% were white and 78% ex-smokers. The mean FEV1 at baseline was 1.7 L and the mean FEV1 % of predicted was 51.3%. The mean follow-up time was 41.7 months. A total of 124 (76% patients received augmentation therapy (augmented group while 40 patients (24% did not received it (non-augmented group. When adjusted by age at baseline, sex, smoking status, baseline FEV1 % of predicted, the mean overall change in FEV1 was 47.6 mL/year, favoring the augmented group (?FEV1 10.6 ± 21.4 mL/year in comparison with the non-augmented group (?FEV1 −36.96 ± 12.1 mL/year (P = 0.05. Beneficial ?FEV1 were observed in ex-smokers and the group with initial FEV1 % of predicted of <50%. No differences were observed in mortality.Conclusions: In conclusion, augmentation therapy improves lung function in subjects with AATD when adjusted by age, gender, smoking status and baseline FEV1 % of predicted. The beneficial
Directory of Open Access Journals (Sweden)
Charlotta Nilsson
Full Text Available We compared safety and immunogenicity of intradermal (ID vaccination with and without electroporation (EP in a phase I randomized placebo-controlled trial of an HIV-DNA prime HIV-MVA boost vaccine in healthy Swedish volunteers.HIV-DNA plasmids encoding HIV-1 genes gp160 subtypes A, B and C; Rev B; Gag A and B and RTmut B were given ID at weeks 0, 6 and 12 in a dose of 0.6 mg. Twenty-five volunteers received vaccine using a needle-free device (ZetaJet with (n=16 or without (n=9 ID EP (Dermavax. Five volunteers were placebo recipients. Boosting with recombinant MVA-CMDR expressing HIV-1 Env, Gag, Pol of CRF01_AE (HIV-MVA or placebo was performed at weeks 24 and 40. Nine of the vaccinees received a subtype C CN54 gp140 protein boost together with HIV-MVA.The ID/EP delivery was very well tolerated. After three HIV-DNA immunizations, no statistically significant difference was seen in the IFN-γ ELISpot response rate to Gag between HIV-DNA ID/EP recipients (5/15, 33% and HIV-DNA ID recipients (1/7, 14%, p=0.6158. The first HIV-MVA or HIV-MVA+gp140 vaccination increased the IFN-γ ELISpot response rate to 18/19 (95%. CD4+ and/or CD8+ T cell responses to Gag or Env were demonstrable in 94% of vaccinees. A balanced CD4+ and CD8+ T cell response was noted, with 78% and 71% responders, respectively. IFN-γ and IL-2 dominated the CD4+ T cell response to Gag and Env. The CD8+ response to Gag was broader with expression of IFN-γ, IL-2, MIP-1β and/or CD107. No differences were seen between DNA vaccine groups. Binding antibodies were induced after the second HIV-MVA+/-gp140 in 93% of vaccinees to subtype C Env, with the highest titers among EP/gp140 recipients.Intradermal electroporation of HIV-DNA was well tolerated. Strong cell- and antibody-mediated immune responses were elicited by the HIV-DNA prime and HIV-MVA boosting regimen, with or without intradermal electroporation use.International Standard Randomised Controlled Trial Number (ISRCTN 60284968.
Nilsson, Charlotta; Hejdeman, Bo; Godoy-Ramirez, Karina; Tecleab, Teghesti; Scarlatti, Gabriella; Bråve, Andreas; Earl, Patricia L; Stout, Richard R; Robb, Merlin L; Shattock, Robin J; Biberfeld, Gunnel; Sandström, Eric; Wahren, Britta
2015-01-01
We compared safety and immunogenicity of intradermal (ID) vaccination with and without electroporation (EP) in a phase I randomized placebo-controlled trial of an HIV-DNA prime HIV-MVA boost vaccine in healthy Swedish volunteers. HIV-DNA plasmids encoding HIV-1 genes gp160 subtypes A, B and C; Rev B; Gag A and B and RTmut B were given ID at weeks 0, 6 and 12 in a dose of 0.6 mg. Twenty-five volunteers received vaccine using a needle-free device (ZetaJet) with (n=16) or without (n=9) ID EP (Dermavax). Five volunteers were placebo recipients. Boosting with recombinant MVA-CMDR expressing HIV-1 Env, Gag, Pol of CRF01_AE (HIV-MVA) or placebo was performed at weeks 24 and 40. Nine of the vaccinees received a subtype C CN54 gp140 protein boost together with HIV-MVA. The ID/EP delivery was very well tolerated. After three HIV-DNA immunizations, no statistically significant difference was seen in the IFN-γ ELISpot response rate to Gag between HIV-DNA ID/EP recipients (5/15, 33%) and HIV-DNA ID recipients (1/7, 14%, p=0.6158). The first HIV-MVA or HIV-MVA+gp140 vaccination increased the IFN-γ ELISpot response rate to 18/19 (95%). CD4+ and/or CD8+ T cell responses to Gag or Env were demonstrable in 94% of vaccinees. A balanced CD4+ and CD8+ T cell response was noted, with 78% and 71% responders, respectively. IFN-γ and IL-2 dominated the CD4+ T cell response to Gag and Env. The CD8+ response to Gag was broader with expression of IFN-γ, IL-2, MIP-1β and/or CD107. No differences were seen between DNA vaccine groups. Binding antibodies were induced after the second HIV-MVA+/-gp140 in 93% of vaccinees to subtype C Env, with the highest titers among EP/gp140 recipients. Intradermal electroporation of HIV-DNA was well tolerated. Strong cell- and antibody-mediated immune responses were elicited by the HIV-DNA prime and HIV-MVA boosting regimen, with or without intradermal electroporation use. International Standard Randomised Controlled Trial Number (ISRCTN) 60284968.
Shafaghat, Farzaneh; Abbasi-Kenarsari, Hajar; Majidi, Jafar; Movassaghpour, Ali Akbar; Shanehbandi, Dariush; Kazemi, Tohid
2015-01-01
Purpose: Transmembrane CD34 glycoprotein is the most important marker for identification, isolation and enumeration of hematopoietic stem cells (HSCs). We aimed in this study to clone the cDNA coding for human CD34 from KG1a cell line and stably express in mouse fibroblast cell line NIH-3T3. Such artificial cell line could be useful as proper immunogen for production of mouse monoclonal antibodies. Methods: CD34 cDNA was cloned from KG1a cell line after total RNA extraction and cDNA synthesis. Pfu DNA polymerase-amplified specific band was ligated to pGEMT-easy TA-cloning vector and sub-cloned in pCMV6-Neo expression vector. After transfection of NIH-3T3 cells using 3 μg of recombinant construct and 6 μl of JetPEI transfection reagent, stable expression was obtained by selection of cells by G418 antibiotic and confirmed by surface flow cytometry. Results: 1158 bp specific band was aligned completely to reference sequence in NCBI database corresponding to long isoform of human CD34. Transient and stable expression of human CD34 on transfected NIH-3T3 mouse fibroblast cells was achieved (25% and 95%, respectively) as shown by flow cytometry. Conclusion: Cloning and stable expression of human CD34 cDNA was successfully performed and validated by standard flow cytometric analysis. Due to murine origin of NIH-3T3 cell line, CD34-expressing NIH-3T3 cells could be useful as immunogen in production of diagnostic monoclonal antibodies against human CD34. This approach could bypass the need for purification of recombinant proteins produced in eukaryotic expression systems. PMID:25789221
Directory of Open Access Journals (Sweden)
Beryl A Koblin
Full Text Available In the development of HIV vaccines, improving immunogenicity while maintaining safety is critical. Route of administration can be an important factor.This multicenter, open-label, randomized trial, HVTN 069, compared routes of administration on safety and immunogenicity of a DNA vaccine prime given intramuscularly at 0, 1 and 2 months and a recombinant replication-defective adenovirus type 5 (rAd5 vaccine boost given at 6 months by intramuscular (IM, intradermal (ID, or subcutaneous (SC route. Randomization was computer-generated by a central data management center; participants and staff were not blinded to group assignment. The outcomes were vaccine reactogenicity and humoral and cellular immunogenicity. Ninety healthy, HIV-1 uninfected adults in the US and Peru, aged 18-50 were enrolled and randomized. Due to the results of the Step Study, injections with rAd5 vaccine were halted; thus 61 received the booster dose of rAd5 vaccine (IM: 20; ID:21; SC:20. After the rAd5 boost, significant differences by study arm were found in severity of headache, pain and erythema/induration. Immune responses (binding and neutralizing antibodies, IFN-γ ELISpot HIV-specific responses and CD4+ and CD8+ T-cell responses by ICS at four weeks after the rAd5 booster were not significantly different by administration route of the rAd5 vaccine boost (Binding antibody responses: IM: 66.7%; ID: 70.0%; SC: 77.8%; neutralizing antibody responses: IM: 11.1%; ID: 0.0%; SC 16.7%; ELISpot responses: IM: 46.7%; ID: 35.3%; SC: 44.4%; CD4+ T-cell responses: IM: 29.4%; ID: 20.0%; SC: 35.3%; CD8+ T-cell responses: IM: 29.4%; ID: 16.7%; SC: 50.0%.This study was limited by the reduced sample size. The higher frequency of local reactions after ID and SC administration and the lack of sufficient evidence to show that there were any differences in immunogenicity by route of administration do not support changing route of administration for the rAd5 boost.ClinicalTrials.gov NCT00384787.
Du, Sean X.; Xu, Li; Zhang, Wenge; Tang, Susan; Boenig, Rebecca I.; Chen, Helen; Mariano, Ellaine B.; Zwick, Michael B.; Parren, Paul W. H. I.; Burton, Dennis R.; Wrin, Terri; Petropoulos, Christos J.; Ballantyne, John A.; Chambers, Michael; Whalen, Robert G.
2011-01-01
A prophylactic vaccine is needed to slow the spread of HIV-1 infection. Optimization of the wild-type envelope glycoproteins to create immunogens that can elicit effective neutralizing antibodies is a high priority. Starting with ten genes encoding subtype B HIV-1 gp120 envelope glycoproteins and using in vitro homologous DNA recombination, we created chimeric gp120 variants that were screened for their ability to bind neutralizing monoclonal antibodies. Hundreds of variants were identified with novel antigenic phenotypes that exhibit considerable sequence diversity. Immunization of rabbits with these gp120 variants demonstrated that the majority can induce neutralizing antibodies to HIV-1. One novel variant, called ST-008, induced significantly improved neutralizing antibody responses when assayed against a large panel of primary HIV-1 isolates. Further study of various deletion constructs of ST-008 showed that the enhanced immunogenicity results from a combination of effective DNA priming, an enhanced V3-based response, and an improved response to the constant backbone sequences. PMID:21738594
Specific microtubule-depolymerizing agents augment efficacy of dendritic cell-based cancer vaccines
Directory of Open Access Journals (Sweden)
Chang Wei-Ting
2011-06-01
Full Text Available Abstract Background Damage-associated molecular patterns (DAMPs are associated with immunogenic cell death and have the ability to enhance maturation and antigen presentation of dendritic cells (DCs. Specific microtubule-depolymerizing agents (MDAs such as colchicine have been shown to confer anti-cancer activity and also trigger activation of DCs. Methods In this study, we evaluated the ability of three MDAs (colchicine and two 2-phenyl-4-quinolone analogues to induce immunogenic cell death in test tumor cells, activate DCs, and augment T-cell proliferation activity. These MDAs were further evaluated for use as an adjuvant in a tumor cell lysate-pulsed DC vaccine. Results The three test phytochemicals considerably increased the expression of DAMPs including HSP70, HSP90 and HMGB1, but had no effect on expression of calreticulin (CRT. DC vaccines pulsed with MDA-treated tumor cell lysates had a significant effect on tumor growth, showed cytotoxic T-lymphocyte activity against tumors, and increased the survival rate of test mice. In vivo antibody depletion experiments suggested that CD8+ and NK cells, but not CD4+ cells, were the main effector cells responsible for the observed anti-tumor activity. In addition, culture of DCs with GM-CSF and IL-4 during the pulsing and stimulation period significantly increased the production of IL-12 and decreased production of IL-10. MDAs also induced phenotypic maturation of DCs and augmented CD4+ and CD8+ T-cell proliferation when co-cultured with DCs. Conclusions Specific MDAs including the clinical drug, colchicine, can induce immunogenic cell death in tumor cells, and DCs pulsed with MDA-treated tumor cell lysates (TCLs can generate potent anti-tumor immunity in mice. This approach may warrant future clinical evaluation as a cancer vaccine.
Liao, Jing-Fong; Lee, Jin-Ching; Lin, Chun-Kuang; Wei, Kuo-Chen; Chen, Pin-Yuan; Yang, Hung-Wei
2017-01-01
The strong immunogenicity induction is the powerful weapon to prevent the virus infections. This study demonstrated that one-step synthesis of DNA polyplex vaccine in microneedle (MN) patches can induce high immunogenicity through intradermal vaccination and increase the vaccine stability for storage outside the cold chain. More negative charged DNA vaccine was entrapped into the needle region of MNs followed by DNA polyplex formation with branched polyethylenimine (bPEI) pre-coated in the cavities of polydimethylsiloxane (PDMS) molds that can deliver more DNA vaccine to immune-cell rich epidermis with high transfection efficiency. Our data in this study support the safety and immunogenicity of the MN-based vaccine; the MN patch delivery system induced an immune response 3.5-fold as strong as seen with conventional intramuscular administration; the DNA polyplex formulation provided excellent vaccine stability at high temperature (could be stored at 45ºC for at least 4 months); the DNA vaccine is expected to be manufactured at low cost and not generate sharps waste. We think this study is significant to public health because there is a pressing need for an effective vaccination in developing countries. PMID:28819449
Fuchs, Jonathan D; Bart, Pierre-Alexandre; Frahm, Nicole; Morgan, Cecilia; Gilbert, Peter B; Kochar, Nidhi; DeRosa, Stephen C; Tomaras, Georgia D; Wagner, Theresa M; Baden, Lindsey R; Koblin, Beryl A; Rouphael, Nadine G; Kalams, Spyros A; Keefer, Michael C; Goepfert, Paul A; Sobieszczyk, Magdalena E; Mayer, Kenneth H; Swann, Edith; Liao, Hua-Xin; Haynes, Barton F; Graham, Barney S; McElrath, M Juliana
2015-05-01
Recombinant adenovirus serotype 5 (rAd5)-vectored HIV-1 vaccines have not prevented HIV-1 infection or disease and pre-existing Ad5 neutralizing antibodies may limit the clinical utility of Ad5 vectors globally. Using a rare Ad serotype vector, such as Ad35, may circumvent these issues, but there are few data on the safety and immunogenicity of rAd35 directly compared to rAd5 following human vaccination. HVTN 077 randomized 192 healthy, HIV-uninfected participants into one of four HIV-1 vaccine/placebo groups: rAd35/rAd5, DNA/rAd5, and DNA/rAd35 in Ad5-seronegative persons; and DNA/rAd35 in Ad5-seropositive persons. All vaccines encoded the HIV-1 EnvA antigen. Antibody and T-cell responses were measured 4 weeks post boost immunization. All vaccines were generally well tolerated and similarly immunogenic. As compared to rAd5, rAd35 was equally potent in boosting HIV-1-specific humoral and cellular immunity and responses were not significantly attenuated in those with baseline Ad5 seropositivity. Like DNA, rAd35 efficiently primed rAd5 boosting. All vaccine regimens tested elicited cross-clade antibody responses, including Env V1/V2-specific IgG responses. Vaccine antigen delivery by rAd35 is well-tolerated and immunogenic as a prime to rAd5 immunization and as a boost to prior DNA immunization with the homologous insert. Further development of rAd35-vectored prime-boost vaccine regimens is warranted.
Geisbert, Thomas W.; Bailey, Michael; Geisbert, Joan B.; Asiedu, Clement; Roederer, Mario; Grazia-Pau, Maria; Custers, Jerome; Jahrling, Peter; Goudsmit, Jaap; Koup, Richard; Sullivan, Nancy J.
2010-01-01
The immunogenicity and durability of genetic vaccines are influenced by the composition of gene inserts and choice of delivery vector. DNA vectors are a promising vaccine approach showing efficacy when combined in prime-boost regimens with recombinant protein or viral vectors, but they have shown
Immunogenic and non-immunogenic hyperthyroidism - a comparison
International Nuclear Information System (INIS)
Pohl, M.; Emrich, D.
1993-01-01
In a retrospective study 161 hyperthyroid patients without treatment were divided into 74 with immunogenic hyperthyroidism (IMH) and 87 with non-immunogenic hypethyroidism (NIMH). The frequency of complaints and the mean hormone concentrations were significantly higher in IMH and the median thyroid volume was significantly smaller. Diffusely reduced sonographic echos were observed in only 50% of patients with IMH compared to 5% of those with NIMH. Homogenous distribution of 99m Tc in the thyroid was observed scintigraphically in 95% of patients with IMH and in only 3% of those with NIMH. Although the median of global thyroid uptake of 99m Tc was significantly higher in IMH there was a broad overlap between the two groups. The mean hormone production is higher in IMH than in NIMH. In order to separate IMH and NIMH, several criteria have to be employed which differ concerning their diagnostic significance. (orig.) [de
Energy Technology Data Exchange (ETDEWEB)
Pohl, M. (Abt. Nuklearmedizin in Zentrum Radiologie, Georg-August-Univ., Goettingen (Germany)); Emrich, D. (Abt. Nuklearmedizin in Zentrum Radiologie, Georg-August-Univ., Goettingen (Germany))
1993-08-01
In a retrospective study 161 hyperthyroid patients without treatment were divided into 74 with immunogenic hyperthyroidism (IMH) and 87 with non-immunogenic hypethyroidism (NIMH). The frequency of complaints and the mean hormone concentrations were significantly higher in IMH and the median thyroid volume was significantly smaller. Diffusely reduced sonographic echos were observed in only 50% of patients with IMH compared to 5% of those with NIMH. Homogenous distribution of [sup 99m]Tc in the thyroid was observed scintigraphically in 95% of patients with IMH and in only 3% of those with NIMH. Although the median of global thyroid uptake of [sup 99m]Tc was significantly higher in IMH there was a broad overlap between the two groups. The mean hormone production is higher in IMH than in NIMH. In order to separate IMH and NIMH, several criteria have to be employed which differ concerning their diagnostic significance. (orig.)
Estrogen receptor accessory proteins augment receptor-DNA interaction and DNA bending.
Landel, C C; Potthoff, S J; Nardulli, A M; Kushner, P J; Greene, G L
1997-01-01
Increasing evidence suggests that accessory proteins play an important role in the ability of the estrogen receptor (ER) and other nuclear hormone receptors to modulate transcription when bound to cis-acting hormone response elements in target genes. We have previously shown that four proteins, hsp70, protein disulfide isomerase (PDI) and two unknown proteins (p48 and p45), copurify with ER that has been isolated by site-specific DNA chromatography (BERE) and influence the interaction of ER with DNA in vitro. To better define the nature of these effects, we used filter binding and electrophoretic mobility shift assays to study the ability of these proteins to alter the kinetics of ER-DNA interaction and to influence the ability of ER to bend DNA when bound to an estrogen response element (ERE). The results of both assays indicate that ERE-purified ER, with its four associated proteins (hsp70, PDI, p48, p45), has a greater ability to bind to the vitellogenin A2 ERE than ER purified by estradiol-Sepharose chromatography in the absence (ESeph) or presence (EATP) of ATP, in which p48, p45 (ESeph) and hsp70 (EATP) are removed. Surprisingly, the rates of association and dissociation of ER and ERE were essentially the same for all three mixtures, suggesting that one or more ER-associated proteins, especially p45 and p48, may be required for ER to attain maximum DNA binding activity. In addition, circular permutation and phasing analyses demonstrated that the same ER-associated proteins produced higher order ER-DNA complexes that significantly increased the magnitude of DNA distortion, but did not alter the direction of the ER-induced bend of ERE-containing DNA fragments, which was toward the major groove of the DNA helix. These results suggest that p45 and/or p48 and possibly hsp70, play an important role both in the specific DNA binding and bending activities of ER and thus contribute to the overall stimulation of transcription in target genes that contain cis
Immunogenicity of therapeutic proteins: the use of animal models.
Brinks, Vera; Jiskoot, Wim; Schellekens, Huub
2011-10-01
Immunogenicity of therapeutic proteins lowers patient well-being and drastically increases therapeutic costs. Preventing immunogenicity is an important issue to consider when developing novel therapeutic proteins and applying them in the clinic. Animal models are increasingly used to study immunogenicity of therapeutic proteins. They are employed as predictive tools to assess different aspects of immunogenicity during drug development and have become vital in studying the mechanisms underlying immunogenicity of therapeutic proteins. However, the use of animal models needs critical evaluation. Because of species differences, predictive value of such models is limited, and mechanistic studies can be restricted. This review addresses the suitability of animal models for immunogenicity prediction and summarizes the insights in immunogenicity that they have given so far.
Directory of Open Access Journals (Sweden)
Viraj Kulkarni
Full Text Available Viral diversity is considered a major impediment to the development of an effective HIV-1 vaccine. Despite this diversity, certain protein segments are nearly invariant across the known HIV-1 Group M sequences. We developed immunogens based on the highly conserved elements from the p24(gag region according to two principles: the immunogen must (i include strictly conserved elements of the virus that cannot mutate readily, and (ii exclude both HIV regions capable of mutating without limiting virus viability, and also immunodominant epitopes located in variable regions. We engineered two HIV-1 p24(gag DNA immunogens that express 7 highly Conserved Elements (CE of 12-24 amino acids in length and differ by only 1 amino acid in each CE ('toggle site', together covering >99% of the HIV-1 Group M sequences. Altering intracellular trafficking of the immunogens changed protein localization, stability, and also the nature of elicited immune responses. Immunization of C57BL/6 mice with p55(gag DNA induced poor, CD4(+ mediated cellular responses, to only 2 of the 7 CE; in contrast, vaccination with p24CE DNA induced cross-clade reactive, robust T cell responses to 4 of the 7 CE. The responses were multifunctional and composed of both CD4(+ and CD8(+ T cells with mature cytotoxic phenotype. These findings provide a method to increase immune response to universally conserved Gag epitopes, using the p24CE immunogen. p24CE DNA vaccination induced humoral immune responses similar in magnitude to those induced by p55(gag, which recognize the virus encoded p24(gag protein. The inclusion of DNA immunogens composed of conserved elements is a promising vaccine strategy to induce broader immunity by CD4(+ and CD8(+ T cells to additional regions of Gag compared to vaccination with p55(gag DNA, achieving maximal cross-clade reactive cellular and humoral responses.
Directory of Open Access Journals (Sweden)
Qiang Zou
2010-01-01
Full Text Available Various chemokines and cytokines as adjuvants can be used to improve efficacy of DNA vaccination. In this study, we sought to investigate if a DNA construct expressing IL-9 (designed as proV-IL9 as a molecular adjuvant enhance antigen specific immune responses elicited by the pcD-VP1 DNA vaccination. Mice immunized with pcD-VP1 combined with proV-IL9 developed a strong humoral response. In addition, the coinoculation induced significant higher level of antigen-specific cell proliferation and cytotoxic response. This agreed well with higher expression level of IFN-γ and perforin in CD8+ T cells, but not with IL-17 in these T cells. The results indicate that IL-9 induces the development of IFN-γ-producing CD8+ T cells (Tc1, but not the IL-17-producing CD8+ T cells (Tc17. Up-regulated expressions of BCL-2 and BCL-XL were exhibited in these Tc1 cells, suggesting that IL-9 may trigger antiapoptosis mechanism in these cells. Together, these results demonstrated that IL-9 used as molecular adjuvant could enhance the immunogenicity of DNA vaccination, in augmenting humoral and cellular responses and particularly promoting Tc1 activations. Thus, the IL-9 may be utilized as a potent Tc1 adjuvant for DNA vaccines.
Preclinical models used for immunogenicity prediction of therapeutic proteins.
Brinks, Vera; Weinbuch, Daniel; Baker, Matthew; Dean, Yann; Stas, Philippe; Kostense, Stefan; Rup, Bonita; Jiskoot, Wim
2013-07-01
All therapeutic proteins are potentially immunogenic. Antibodies formed against these drugs can decrease efficacy, leading to drastically increased therapeutic costs and in rare cases to serious and sometimes life threatening side-effects. Many efforts are therefore undertaken to develop therapeutic proteins with minimal immunogenicity. For this, immunogenicity prediction of candidate drugs during early drug development is essential. Several in silico, in vitro and in vivo models are used to predict immunogenicity of drug leads, to modify potentially immunogenic properties and to continue development of drug candidates with expected low immunogenicity. Despite the extensive use of these predictive models, their actual predictive value varies. Important reasons for this uncertainty are the limited/insufficient knowledge on the immune mechanisms underlying immunogenicity of therapeutic proteins, the fact that different predictive models explore different components of the immune system and the lack of an integrated clinical validation. In this review, we discuss the predictive models in use, summarize aspects of immunogenicity that these models predict and explore the merits and the limitations of each of the models.
National Research Council Canada - National Science Library
Dowling, William; Thompson, Elizabeth; Badger, Catherine; Mellquist, Jenny L; Garrison, Aura R; Smith, Jeffrey M; Paragas, Jason; Hogan, Robert J; Schmaljohn, Connie
2006-01-01
... or with deletions in the central hypervariable mucin region. We showed that mutation of one of the two N-linked GP2 glycosylation sites was highly detrimental to the antigenicity and immunogenicity of GP...
International Nuclear Information System (INIS)
Gasparro, F.P.; Santella, R.M.
1988-01-01
The direct photomodification of DNA by ultraviolet light or the photo-induced addition of exogenous compounds to DNA components results in alterations of DNA structure ranging from subtle to profound. There are two consequences of these conformational changes. First, cells in which the DNA has been damaged are capable of executing repair steps. Second, the DNA which is usually of very low immunogenicity now becomes highly antigenic. This latter property has allowed the production of a series of monoclonal antibodies that recognize photo-induced DNA damage. Monoclonal antibodies have been generated that recognize the 4',5'-monoadduct and the crosslink of 8-methoxypsoralen in DNA. In addition, another antibody has been prepared which recognizes the furan-side monoadduct of 6,4,4'-trimethylangelicin in DNA. These monoclonal antibodies have been characterized as to sensitivity and specificity using non-competitive and competitive enzyme-linked-immunosorbent assays (ELISA). (author)
Energy Technology Data Exchange (ETDEWEB)
Gasparro, F P; Santella, R M
1988-09-01
The direct photomodification of DNA by ultraviolet light or the photo-induced addition of exogenous compounds to DNA components results in alterations of DNA structure ranging from subtle to profound. There are two consequences of these conformational changes. First, cells in which the DNA has been damaged are capable of executing repair steps. Second, the DNA which is usually of very low immunogenicity now becomes highly antigenic. This latter property has allowed the production of a series of monoclonal antibodies that recognize photo-induced DNA damage. Monoclonal antibodies have been generated that recognize the 4',5'-monoadduct and the crosslink of 8-methoxypsoralen in DNA. In addition, another antibody has been prepared which recognizes the furan-side monoadduct of 6,4,4'-trimethylangelicin in DNA. These monoclonal antibodies have been characterized as to sensitivity and specificity using non-competitive and competitive enzyme-linked-immunosorbent assays (ELISA).
Directory of Open Access Journals (Sweden)
Matthew P Morrow
2016-01-01
Full Text Available We have previously demonstrated the immunogenicity of VGX-3100, a multicomponent DNA immunotherapy for the treatment of Human Papillomavirus (HPV16/18-positive CIN2/3 in a phase 1 clinical trial. Here, we report on the ability to boost immune responses with an additional dose of VGX-3100. Patients completing our initial phase 1 trial were offered enrollment into a follow on trial consisting of a single boost dose of VGX-3100. Data show both cellular and humoral immune responses could be augmented above pre-boost levels, including the induction of interferon (IFNγ production, tumor necrosis factor (TNFα production, CD8+ T cell activation and the synthesis of lytic proteins. Moreover, observation of antigen-specific regulation of immune-related gene transcripts suggests the induction of a proinflammatory response following the boost. Analysis of T cell receptor (TCR sequencing suggests the localization of putative HPV-specific T cell clones to the cervical mucosa, which underscores the putative mechanism of action of lesion regression and HPV16/18 elimination noted in our double-blind placebo-controlled phase 2B trial. Taken together, these data indicate that VGX-3100 drives the induction of robust cellular and humoral immune responses that can be augmented by a fourth “booster” dose. These data could be important in the scope of increasing the clinical efficacy rate of VGX-3100.
Immunogenic hyperthyroidism following radioiodine ablation of focal autonomy
International Nuclear Information System (INIS)
Boddenberg, B.; Voth, E.; Schicha, H.
1993-01-01
Immunogenic hyperthyroidism rarely develops after radioiodine elimination of focal autonomous thyroid tissue. We observed this phenomenon in 8 patients between 1989 and 1992. The occurrence of immunogenic hyperthyroidism shortly after elimination of autonomous nodules has not been studied nor is it properly understood. Most studies known today describe the development of autonomous nodules in the course of immunogenic hyperthyroidism or ignore the chronologic order of occurrence. The possibility that immunogenic hyperthyroidism may occur after radioiodine therapy of autonomous nodules, makes a consequent follow-up within the first year following radioiodine therapy mandatory. (orig.) [de
LENUS (Irish Health Repository)
Whelan, M C
2012-01-31
Obstacles to effective immunotherapeutic anti-cancer approaches include poor immunogenicity of the tumour cells and the presence of tolerogenic mechanisms in the tumour microenvironment. We report an effective immune-based treatment of weakly immunogenic, growing solid tumours using a locally delivered immunogene therapy to promote development of immune effector responses in the tumour microenvironment and a systemic based T regulatory cell (Treg) inactivation strategy to potentiate these responses by elimination of tolerogenic or immune suppressor influences. As the JBS fibrosarcoma is weakly immunogenic and accumulates Treg in its microenvironment with progressive growth, we used this tumour model to test our combined immunotherapies. Plasmids encoding GM-CSF and B7-1 were electrically delivered into 100 mm(3) tumours; Treg inactivation was accomplished by systemic administration of anti-CD25 antibody (Ab). Using this approach, we found that complete elimination of tumours was achieved at a level of 60% by immunogene therapy, 25% for Treg inactivation and 90% for combined therapies. Moreover, we found that these responses were immune transferable, systemic, tumour specific and durable. Combined gene-based immune effector therapy and Treg inactivation represents an effective treatment for weakly antigenic solid growing tumours and that could be considered for clinical development.
Ma, Fengying; Zou, Haoyong; He, Qigai
2011-09-01
The study was carried out to construct and characterize Salmonella choleraesuis vaccine strain expressing immunogenic genes of Mycoplasma hyopneumoniae and to test its immunogenicity in mice. We made p36, p46, p65 and p97R1-Nrdf, the main immunogenic genes of Mycoplasma hyopneumoniae, to insert into the prokaryotic expression plasmid pYA3493. Then these recombinant plasmids and pYA3493 were electroporated into C500 asd-mutant, resulting in the recombinant Salmonella choleraesuis vaccine strains C36 (pYA-36), C46 (pYA-46), C65 (pYA-65), C97R1-Nrdf(pYA-97R1-Nrdf) and CpYA(pYA3493). We characterized these recombinant Salmonella choleraesuis vaccine strains and tested the immunogenicity in mice by intramuscular injection or orally immunized. The results of the immunogenicity in mice indicated that the group orally immunized with C36, C46, C65, C97R1-Nrdf showed significantly higher Mycoplasma pneumoniae antibody than both the group orally immunized with C36, C46, C65 and the group intramuscular injected with the Mycoplasma hyopneumoniae bacterin (M + PAC) (P Mycoplasma hyopneumoniae bacterin (M + PAC) (P 0.05). The highest level of IL-4 was found in the group orally immunized with C36, C46, C65; higher levels of IL-4 was observed in the group orally immunized with C36, C46, C65, C97R1-Nrdf than the group injected with the Mycoplasma hyopneumoniae bacterin (M + PAC); and the lowest IL-4 level was found in the group injected with C36, C46, C65. There were no significant differences among them (P > 0.05). The Mycoplasma pneumoniae antibody, IFN-gamma or IL-4 production of the each group was obviously higher than the control group (P Mycoplasma hyopneumoniae which has immunogenicity in mice especially by intramuscular injection could probably serve as a vaccine against mycoplasmal pneumonia of swine.
Mosaic HIV envelope immunogenic polypeptides
Korber, Bette T. M.; Gnanakaran, S.; Perkins, Simon; Sodroski, Joseph; Haynes, Barton
2018-01-02
Disclosed herein are mosaic HIV envelope (Env) polypeptides that can elicit an immune response to HIV (such as cytotoxic T cell (CTL), helper T cell, and/or humoral responses). Also disclosed are sets of the disclosed mosaic Env polypeptides, which include two or more (for example, three) of the polypeptides. Also disclosed herein are methods for treating or inhibiting HIV in a subject including administering one or more of the disclosed immunogenic polypeptides or compositions to a subject infected with HIV or at risk of HIV infection. In some embodiments, the methods include inducing an immune response to HIV in a subject comprising administering to the subject at least one (such as two, three, or more) of the immunogenic polypeptides or at least one (such as two, three, or more) nucleic acids encoding at least one of the immunogenic polypeptides disclosed herein.
Immunogenicity and immunomodulatory properties of umbilical cord lining mesenchymal stem cells.
Deuse, Tobias; Stubbendorff, Mandy; Tang-Quan, Karis; Phillips, Neil; Kay, Mark A; Eiermann, Thomas; Phan, Thang T; Volk, Hans-Dieter; Reichenspurner, Hermann; Robbins, Robert C; Schrepfer, Sonja
2011-01-01
We here present an immunologic head-to-head comparison between human umbilical cord lining mesenchymal stem cells (clMSCs) and adult bone marrow MSCs (bmMSCs) from patients >65 years of age. clMSCs had significantly lower HLA class I expression, higher production of tolerogenic TGF-β and IL-10, and showed significantly faster proliferation. In vitro activation of allogeneic lymphocytes and xenogeneic in vivo immune activation was significantly stronger with bmMSCs, whereas immune recognition of clMSCs was significantly weaker. Thus, bmMSCs were more quickly rejected in immunocompetent mice. IFN-γ at 25 ng/ml increased both immunogenicity by upregulation of HLA class I/ HLA-DR expression and tolerogenicity by increasing intracellular HLA-G and surface HLA-E expression, augmenting TGF-β and IL-10 release, and inducing indoleamine 2,3-dioxygenase (IDO) expression. Higher concentrations of IFN-γ (>50 ng/ml) further enhanced the immunosuppressive phenotype of clMSCs, more strongly downregulating HLA-DR expression and further increasing IDO production (at 500 ng/ml). The net functional immunosuppressive efficacy of MSCs was tested in mixed lymphocyte cultures. Although both clMSCs and bmMSCs significantly reduced in vitro immune activation, clMSCs were significantly more effective than bmMSCs. The veto function of both MSC lines was enhanced in escalating IFN-γ environments. In conclusion, clMSCs show a more beneficial immunogeneic profile and stronger overall immunosuppressive potential than aged bmMSCs.
Identification of an Immunogenic Subset of Metastatic Uveal Melanoma.
Rothermel, Luke D; Sabesan, Arvind C; Stephens, Daniel J; Chandran, Smita S; Paria, Biman C; Srivastava, Abhishek K; Somerville, Robert; Wunderlich, John R; Lee, Chyi-Chia R; Xi, Liqiang; Pham, Trinh H; Raffeld, Mark; Jailwala, Parthav; Kasoji, Manjula; Kammula, Udai S
2016-05-01
Uveal melanoma is a rare melanoma variant with no effective therapies once metastases develop. Although durable cancer regression can be achieved in metastatic cutaneous melanoma with immunotherapies that augment naturally existing antitumor T-cell responses, the role of these treatments for metastatic uveal melanoma remains unclear. We sought to define the relative immunogenicity of these two melanoma variants and determine whether endogenous antitumor immune responses exist against uveal melanoma. We surgically procured liver metastases from uveal melanoma (n = 16) and cutaneous melanoma (n = 35) patients and compared the attributes of their respective tumor cell populations and their infiltrating T cells (TIL) using clinical radiology, histopathology, immune assays, and whole-exomic sequencing. Despite having common melanocytic lineage, uveal melanoma and cutaneous melanoma metastases differed in their melanin content, tumor differentiation antigen expression, and somatic mutational profile. Immunologic analysis of TIL cultures expanded from these divergent forms of melanoma revealed cutaneous melanoma TIL were predominantly composed of CD8(+) T cells, whereas uveal melanoma TIL were CD4(+) dominant. Reactivity against autologous tumor was significantly greater in cutaneous melanoma TIL compared with uveal melanoma TIL. However, we identified TIL from a subset of uveal melanoma patients which had robust antitumor reactivity comparable in magnitude with cutaneous melanoma TIL. Interestingly, the absence of melanin pigmentation in the parental tumor strongly correlated with the generation of highly reactive uveal melanoma TIL. The discovery of this immunogenic group of uveal melanoma metastases should prompt clinical efforts to determine whether patients who harbor these unique tumors can benefit from immunotherapies that exploit endogenous antitumor T-cell populations. Clin Cancer Res; 22(9); 2237-49. ©2015 AACR. ©2015 American Association for Cancer Research.
Dahiya, Shyam S; Saini, Mohini; Kumar, Pankaj; Gupta, Praveen K
2012-10-01
A replicon-based DNA vaccine encoding VP2 gene of canine parvovirus (CPV) was developed by cloning CPV-VP2 gene into a replicon-based DNA vaccine vector (pAlpha). The characteristics of a replicon-based DNA vaccine like, self-amplification of transcripts and induction of apoptosis were analyzed in transfected mammalian cells. When the pAlpha-CPV-VP2 was injected intradermal as DNA-launched replicon-based DNA vaccine in dogs, it induced CPV-specific humoral and cell mediated immune responses. The virus neutralization antibody and lymphocyte proliferative responses were higher than conventional CPV DNA vaccine and commercial CPV vaccine. These results indicated that DNA-launched replicon-based CPV DNA vaccine was effective in inducing both CPV-specific humoral and cellular immune responses and can be considered as effective alternative to conventional CPV DNA vaccine and commercial CPV vaccine. Crown Copyright © 2012. Published by Elsevier India Pvt Ltd. All rights reserved.
Energy Technology Data Exchange (ETDEWEB)
M Totrov; X Jiang; X Kong; S Cohen; C Krachmarov; A Salomon; C Williams; M Seaman; R Abagyan; et al.
2011-12-31
V3 loop is a major neutralizing determinant of the HIV-1 gp120. Using 3D structures of cholera toxin B subunit (CTB), complete V3 in the gp120 context, and V3 bound to a monoclonal antibody (mAb), we designed two V3-scaffold immunogen constructs (V3-CTB). The full-length V3-CTB presenting the complete V3 in a structural context mimicking gp120 was recognized by the large majority of our panel of 24 mAbs. The short V3-CTB presenting a V3 fragment in the conformation observed in the complex with the 447-52D Fab, exhibited high-affinity binding to this mAb. The immunogens were evaluated in rabbits using DNA-prime/protein-boost protocol. Boosting with the full-length V3-CTB induced high anti-V3 titers in sera that potently neutralize multiple HIV virus strains. The short V3-CTB was ineffective. The results suggest that very narrow antigenic profile of an immunogen is associated with poor Ab response. An immunogen with broader antigenic activity elicits robust Ab response.
Determinants of immunogenic response to protein therapeutics.
Singh, Satish K; Cousens, Leslie P; Alvarez, David; Mahajan, Pramod B
2012-09-01
Protein therapeutics occupy a very significant position in the biopharmaceutical market. In addition to the preclinical, clinical and post marketing challenges common to other drugs, unwanted immunogenicity is known to affect efficacy and/or safety of most biotherapeutics. A standard set of immunogenicity risk factors are routinely used to inform monitoring strategies in clinical studies. A number of in-silico, in vivo and in vitro approaches have also been employed to predict immunogenicity of biotherapeutics, but with limited success. Emerging data also indicates the role of immune tolerance mechanisms and impact of several product-related factors on modulating host immune responses. Thus, a comprehensive discussion of the impact of innate and adaptive mechanisms and molecules involved in induction of host immune responses on immunogenicity of protein therapeutics is needed. A detailed understanding of these issues is essential in order to fully exploit the therapeutic potential of this class of drugs. This Roundtable Session was designed to provide a common platform for discussing basic immunobiological and pharmacological issues related to the role of biotherapeutic-associated risk factors, as well as host immune system in immunogenicity against protein therapeutics. The session included overview presentations from three speakers, followed by a panel discussion with audience participation. Copyright © 2012. Published by Elsevier Ltd.. All rights reserved.
Huang, L Y; Wang, K Y; Xiao, D; Chen, D F; Geng, Y; Wang, J; He, Y; Wang, E L; Huang, J L; Xiao, G Y
2014-05-01
Attenuated Salmonella typhimurium SL7207 was used as a carrier for a reconstructed DNA vaccine against Streptococcus agalactiae. A 1.02 kb DNA fragment, encoding for a portion of the surface immunogenic protein (Sip) of S. agalactiae was inserted into pVAX1. The recombinant plasmid pVAX1-sip was transfected in EPC cells to detect the transient expression by an indirect immunofluorescence assay, together with Western blot analysis. The pVAX1-sip was transformed by electroporation into SL7207. The stability of pVAX1-sip into Salmonella was over 90% after 50 generations with antibiotic selection in vitro while remained stable over 80% during 35 generations under antibiotic-free conditions. The LD50 of SL/pVAX1-sip was 1.7 × 10(11) CFU/fish by intragastric administration which indicated a quite low virulence. Tilapias were inoculated orally at 10(8) CFU/fish, the recombinant bacteria were found present in intestinal tract, spleens and livers and eventually eliminated from the tissues 4 weeks after immunization. Fish immunized at 10(7), 10(8) and 10(9) CFU/fish with different immunization times caused various levels of serum antibody and an effective protection against lethal challenge with the wild-type strain S. agalactiae. Integration studies showed that the pVAX1-sip did not integrate with tilapia chromosomes. The DNA vaccine SL/pVAX1-sip was proved to be safe and effective in protecting tilapias against S. agalactiae infection. Copyright © 2014 Elsevier Ltd. All rights reserved.
Directory of Open Access Journals (Sweden)
Jyoti Gupta
Full Text Available We earlier demonstrated the immunoprophylactic efficacy of recombinant heavy chain myosin (Bm-Myo of Brugia malayi (B. malayi in rodent models. In the current study, further attempts have been made to improve this efficacy by employing alternate approaches such as homologous DNA (pcD-Myo and heterologous DNA/protein prime boost (pcD-Myo+Bm-Myo in BALB/c mouse model. The gene bm-myo was cloned in a mammalian expression vector pcDNA 3.1(+ and protein expression was confirmed in mammalian Vero cell line. A significant degree of protection (79.2%±2.32 against L3 challenge in pcD-Myo+Bm-Myo immunized group was observed which was much higher than that exerted by Bm-Myo (66.6%±2.23 and pcD-Myo (41.6%±2.45. In the heterologous immunized group, the percentage of peritoneal leukocytes such as macrophages, neutrophils, B cells and T cells marginally increased and their population augmented further significantly following L3 challenge. pcD-Myo+Bm-Myo immunization elicited robust cellular and humoral immune responses as compared to pcD-Myo and Bm-Myo groups as evidenced by an increased accumulation of CD4+, CD8+ T cells and CD19+ B cells in the mouse spleen and activation of peritoneal macrophages. Though immunized animals produced antigen-specific IgG antibodies and isotypes, sera of mice receiving pcD-Myo+Bm-Myo or Bm-Myo developed much higher antibody levels than other groups and there was profound antibody-dependent cellular adhesion and cytotoxicity (ADCC to B. malayi infective larvae (L3. pcD-Myo+Bm-Myo as well as Bm-Myo mice generated a mixed T helper cell phenotype as evidenced by the production of both pro-inflammatory (IL-2, IFN-γ and anti-inflammatory (IL-4, IL-10 cytokines. Mice receiving pcD-Myo on contrary displayed a polarized pro-inflammatory immune response. The findings suggest that the priming of animals with DNA followed by protein booster generates heightened and mixed pro- and anti-inflammatory immune responses that are capable of
Impact of product-related factors on immunogenicity of biotherapeutics.
Singh, Satish Kumar
2011-02-01
All protein therapeutics have the potential to be immunogenic. Several factors, including patient characteristics, disease state, and the therapy itself, influence the generation of an immune response. Product-related factors such as the molecule design, the expression system, post-translational modifications, impurities, contaminants, formulation and excipients, container, closure, as well as degradation products are all implicated. However, a critical examination of the available data shows that clear unequivocal evidence for the impact of these latter factors on clinical immunogenicity is lacking. No report could be found that clearly deconvolutes the clinical impact of the product attributes on patient susceptibility. Aggregation carries the greatest concern as a risk factor for immunogenicity, but the impact of aggregates is likely to depend on their structure as well as on the functionality (e.g., immunostimulatory or immunomodulatory) of the therapeutic. Preclinical studies are not yet capable of assessing the clinically relevant immunogenicity potential of these product-related factors. Simply addressing these risk factors as part of product development will not eliminate immunogenicity. Minimization of immunogenicity has to begin at the molecule design stage by reducing or eliminating antigenic epitopes and building in favorable physical and chemical properties. Copyright © 2010 Wiley-Liss, Inc.
Chimeric infectious DNA clones, chimeric porcine circoviruses and uses thereof
2011-01-01
The present invention relates to infectious DNA clones, infectious chimeric DNA clones of porcine circovirus (PCV), vaccines and means of protecting pigs against viral infection or postweaning multisystemic wasting syndrome (PMWS) caused by PCV2. The new chimeric infectious DNA clone and its derived, avirulent chimeric virus are constructed from the nonpathogenic PCV1 in which the immunogenic ORF gene of the pathogenic PCV2 replaces a gene of the nonpathogenic PCV1, preferably in the same pos...
Cancer vaccine development: Designing tumor cells for greater immunogenicity
Bozeman, Erica N.; Shashidharamurthy, Rangaiah; Paulos, Simon A.; Palaniappan, Ravi; D’Souza, Martin; Selvaraj, Periasamy
2014-01-01
Cancer vaccine development is one of the most hopeful and exhilarating areas in cancer research. For this reason, there has been a growing interest in the development and application of novel immunotherapies for the treatment of cancer with the focus being on stimulating the immune system to target tumor cells specifically while leaving normal cells unharmed. From such research has emerged a host of promising immunotherapies such as dendritic cell-based vaccines, cytokine therapies and gene transfer technology. These therapies seek to counteract the poor immunogenicity of tumors by augmenting the host’s immune system with a variety of immunostimulatory proteins such as cytokines and costimulatory molecules. While such therapies have proven effective in the induction of anti-tumor immunity in animal models, they are less than optimal and pose a high risk of clinical infeasibility. Herein, we further discuss these immunotherapies as well as a feasible and efficient alternative that, in pre-clinical animal models, allows for the expression of specific immunostimulatory molecules on the surface of tumor cells by a novel protein transfer technology. PMID:20036822
Directory of Open Access Journals (Sweden)
Juliet Mpendo
Full Text Available Strategies to enhance the immunogenicity of DNA vaccines in humans include i co-administration of molecular adjuvants, ii intramuscular administration followed by in vivo electroporation (IM/EP and/or iii boosting with a different vaccine. Combining these strategies provided protection of macaques challenged with SIV; this clinical trial was designed to mimic the vaccine regimen in the SIV study.Seventy five healthy, HIV-seronegative adults were enrolled into a phase 1, randomized, double-blind, placebo-controlled trial. Multi-antigenic HIV (HIVMAG plasmid DNA (pDNA vaccine alone or co-administered with pDNA encoding human Interleukin 12 (IL-12 (GENEVAX IL-12 given by IM/EP using the TriGrid Delivery System was tested in different prime-boost regimens with recombinant Ad35 HIV vaccine given IM.All local reactions but one were mild or moderate. Systemic reactions and unsolicited adverse events including laboratory abnormalities did not differ between vaccine and placebo recipients. No serious adverse events (SAEs were reported. T cell and antibody response rates after HIVMAG (x3 prime-Ad35 (x1 boost were independent of IL-12, while the magnitude of interferon gamma (IFN-γ ELISPOT responses was highest after HIVMAG (x3 without IL-12. The quality and phenotype of T cell responses shown by intracellular cytokine staining (ICS were similar between groups. Inhibition of HIV replication by autologous T cells was demonstrated after HIVMAG (x3 prime and was boosted after Ad35. HIV specific antibodies were detected only after Ad35 boost, although there was a priming effect with 3 doses of HIVMAG with or without IL-12. No anti-IL-12 antibodies were detected.The vaccines were safe, well tolerated and moderately immunogenic. Repeated administration IM/EP was well accepted. An adjuvant effect of co-administered plasmid IL-12 was not detected.ClinicalTrials.gov NCT01496989.
Directory of Open Access Journals (Sweden)
Alexandra J Spencer
Full Text Available To prevent important infectious diseases such as tuberculosis, malaria and HIV, vaccines inducing greater T cell responses are required. In this study, we investigated whether fusion of the M. tuberculosis antigen 85A to recently described adjuvant IMX313, a hybrid avian C4bp oligomerization domain, could increase T cell responses in pre-clinical vaccine model species. In mice, the fused antigen 85A showed consistent increases in CD4(+ and CD8(+ T cell responses after DNA and MVA vaccination. In rhesus macaques, higher IFN-γ responses were observed in animals vaccinated with MVA-Ag85A IMX313 after both primary and secondary immunizations. In both animal models, fusion to IMX313 induced a quantitative enhancement in the response without altering its quality: multifunctional cytokines were uniformly increased and differentiation into effector and memory T cell subsets was augmented rather than skewed. An extensive in vivo characterization suggests that IMX313 improves the initiation of immune responses as an increase in antigen 85A specific cells was observed as early as day 3 after vaccination. This report demonstrates that antigen multimerization using IMX313 is a simple and effective cross-species method to improve vaccine immunogenicity with potentially broad applicability.
Multivalent human papillomavirus l1 DNA vaccination utilizing electroporation.
Directory of Open Access Journals (Sweden)
Kihyuck Kwak
Full Text Available Naked DNA vaccines can be manufactured simply and are stable at ambient temperature, but require improved delivery technologies to boost immunogenicity. Here we explore in vivo electroporation for multivalent codon-optimized human papillomavirus (HPV L1 and L2 DNA vaccination.Balb/c mice were vaccinated three times at two week intervals with a fusion protein comprising L2 residues ∼11-88 of 8 different HPV types (11-88×8 or its DNA expression vector, DNA constructs expressing L1 only or L1+L2 of a single HPV type, or as a mixture of several high-risk HPV types and administered utilizing electroporation, i.m. injection or gene gun. Serum was collected two weeks and 3 months after the last vaccination. Sera from immunized mice were tested for in-vitro neutralization titer, and protective efficacy upon passive transfer to naive mice and vaginal HPV challenge. Heterotypic interactions between L1 proteins of HPV6, HPV16 and HPV18 in 293TT cells were tested by co-precipitation using type-specific monoclonal antibodies.Electroporation with L2 multimer DNA did not elicit detectable antibody titer, whereas DNA expressing L1 or L1+L2 induced L1-specific, type-restricted neutralizing antibodies, with titers approaching those induced by Gardasil. Co-expression of L2 neither augmented L1-specific responses nor induced L2-specific antibodies. Delivery of HPV L1 DNA via in vivo electroporation produces a stronger antibody response compared to i.m. injection or i.d. ballistic delivery via gene gun. Reduced neutralizing antibody titers were observed for certain types when vaccinating with a mixture of L1 (or L1+L2 vectors of multiple HPV types, likely resulting from heterotypic L1 interactions observed in co-immunoprecipitation studies. High titers were restored by vaccinating with individual constructs at different sites, or partially recovered by co-expression of L2, such that durable protective antibody titers were achieved for each type
Identification of Novel Immunogenic Proteins of Neisseria gonorrhoeae by Phage Display.
Directory of Open Access Journals (Sweden)
Daniel O Connor
Full Text Available Neisseria gonorrhoeae is one of the most prevalent sexually transmitted diseases worldwide with more than 100 million new infections per year. A lack of intense research over the last decades and increasing resistances to the recommended antibiotics call for a better understanding of gonococcal infection, fast diagnostics and therapeutic measures against N. gonorrhoeae. Therefore, the aim of this work was to identify novel immunogenic proteins as a first step to advance those unresolved problems. For the identification of immunogenic proteins, pHORF oligopeptide phage display libraries of the entire N. gonorrhoeae genome were constructed. Several immunogenic oligopeptides were identified using polyclonal rabbit antibodies against N. gonorrhoeae. Corresponding full-length proteins of the identified oligopeptides were expressed and their immunogenic character was verified by ELISA. The immunogenic character of six proteins was identified for the first time. Additional 13 proteins were verified as immunogenic proteins in N. gonorrhoeae.
Khan, Md Asad; Alam, Khursheed; Mehdi, Syed Hassan; Rizvi, M Moshahid A
2017-12-01
Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease characterized by auto-antibodies against native deoxyribonucleic acid after modification and is one of the reasons for the development of SLE. Here, we have evaluated the structural perturbations in human placental DNA by peroxynitrite using spectroscopy, thermal denaturation and high-performance liquid chromatography (HPLC). Peroxynitrite is a powerful potent bi-functional oxidative/nitrative agent that is produced both endogenously and exogenously. In experimental animals, the peroxynitrite-modified DNA was found to be highly immunogenic. The induced antibodies showed cross-reactions with different types of DNA and nitrogen bases that were modified with peroxynitrite by inhibition ELISA. The antibody activity was inhibited by approximately 89% with its immunogen as the inhibitor. The antigen-antibodies interaction between induced antibodies with peroxynitrite-modified DNA showed retarded mobility as compared to the native form. Furthermore, significantly increased binding was also observed in SLE autoantibodies with peroxynitrite-modified DNA than native form. Moreover, DNA isolated from lymphocyte of SLE patients revealed significant recognition of anti-peroxynitrite-modified DNA immunoglobulin G (IgG). Our data indicates that DNA modified with peroxynitrite presents unique antigenic determinants that may induce autoantibody response in SLE. Copyright © 2017 Elsevier Inc. All rights reserved.
The Comparative Immunogenicity Of Three Lentogenic Brands Of ...
African Journals Online (AJOL)
The comparative immunogenicity of a new lentogenic viscerotropic Newcastle disease vaccine, NDvac-1 (VG/GA strain) and two other existing proprietary pneumotropic lentogenic Newcastle disease vaccines in Nigeria, NDvac-2 (R2B) and NDvac-3 (LaSota) were studied. Immunogenicity was assessed on the basis of ...
Immunogenicity of therapeutic proteins. Part 2: impact of container closures.
Sharma, Basant
2007-01-01
Immunogenicity as a potential consequence of therapeutic protein administration is increasingly being scrutinized in the biopharmaceuticals industry, particularly with the imminent introduction of biosimilar products. Immunogenicity is an important safety aspect requiring rigorous investigation to fully appreciate its impact. Factors involved in product handling, such as storage temperature, light exposure, and shaking, have been implicated in immunogenicity, while container closure systems are no less important. Intended to provide a stable environment for the dosage form, container closures may also interact with a product, affecting performance and potentially enhancing immunogenicity. Glass surfaces, air-liquid interfaces, and lubricants can mediate protein denaturation, while phthalates in plastics and latex rubber are sources of extractables and leachates that may contaminate a product, causing allergic reactions and increasing immunogenicity. The manufacture of therapeutic proteins therefore requires rigorous safety evaluations not just in the context of the product, but also product containment.
Mobile Collaborative Augmented Reality: The Augmented Stroll
Renevier , Philippe; Nigay , Laurence
2001-01-01
International audience; The paper focuses on Augmented Reality systems in which interaction with the real world is augmented by the computer, the task being performed in the real world. We first define what mobile AR systems, collaborative AR systems and finally mobile and collaborative AR systems are. We then present the augmented stroll and its software design as one example of a mobile and collaborative AR system. The augmented stroll is applied to Archaeology in the MAGIC (Mobile Augmente...
Directory of Open Access Journals (Sweden)
Johanna Poecheim
2015-12-01
Full Text Available Adjuvants enhance immunogenicity of vaccines through either targeted antigen delivery or stimulation of immune receptors. Three cationic nanoparticle formulations were evaluated for their potential as carriers for a DNA vaccine, and muramyl dipeptide (MDP as immunostimulatory agent, to induce and increase immunogenicity of Mycobacterium tuberculosis antigen encoding plasmid DNA (pDNA. The formulations included (1 trimethyl chitosan (TMC nanoparticles, (2 a squalene-in-water nanoemulsion, and (3 a mineral oil-in-water nanoemulsion. The adjuvant effect of the pDNA-nanocomplexes was evaluated by serum antibody analysis in immunized mice. All three carriers display a strong adjuvant effect, however, only TMC nanoparticles were capable to bias immune responses towards Th1. pDNA naturally contains immunostimulatory unmethylated CpG motifs that are recognized by Toll-like receptor 9 (TLR-9. In mechanistic in vitro studies, activation of TLR-9 and the ability to enhance immunogenicity by simultaneously targeting TLR-9 and NOD-like receptor 2 (NLR-2 was determined by proinflammatory cytokine release in RAW264.7 macrophages. pDNA in combination with MDP was shown to significantly increase proinflammatory cytokine release in a synergistic manner, dependent on NLR-2 activation. In summary, novel pDNA-Ag85A loaded nanoparticle formulations, which induce antigen specific immune responses in mice were developed, taking advantage of the synergistic combinations of TLR and NLR agonists to increase the adjuvanticity of the carriers used.
Real-Life Efficacy, Immunogenicity and Safety of Biosimilar Infliximab.
Vegh, Zsuzsanna; Kurti, Zsuzsanna; Lakatos, Peter L
2017-01-01
Recently, the use of biosimilar infliximab (IFX) in the treatment of inflammatory bowel diseases has become widespread in some European and non-European countries. Data on the efficacy, safety and immunogenicity from real-life cohorts are accumulating. The first reports showed similar outcomes in the induction and maintenance of remission, mucosal healing, safety and immunogenicity profile to the originator IFX. In the present review, we aimed to summarize the existing knowledge on the efficacy, safety and immunogenicity profile of biosimilar IFX reported from real-life cohorts. © 2017 S. Karger AG, Basel.
High pathogenicity and strong immunogenicity of a Chinese isolate of Eimeria magna Pérard, 1925.
Tao, Geru; Wang, Yunzhou; Li, Chao; Gu, Xiaolong; Cui, Ping; Fang, Sufang; Suo, Xun; Liu, Xianyong
2017-06-01
Coccidia infection of rabbits with one or several species of parasites of the genus Eimeria causes coccidiosis, a disease leading to huge economic losses in the rabbit industry. Eimeria magna, one of the causal agents of rabbit coccidiosis, was characterized as mildly pathogenic and moderately immunogenic in previous studies. In this study, we identified a Chinese isolate of E. magna by testing its biological features (oocyst morphology and size, prepatent time) and sequencing its internal transcribed spacer 1 (ITS-1) DNA fragment. This isolate is highly pathogenic; infection of rabbits with only 1×10 2 oocysts caused a 55% reduction in weight gain in 14days. In addition, immunization with 1×10 2 oocysts prevented body weight loss against re-infection with 5×10 4 oocysts, indicating the high immunogenicity of this isolate. Our study described the distinctive phenotype of the Chinese isolate of E. magna and contributed to the research of geographic variation of rabbit coccidia. Copyright © 2017 Elsevier B.V. All rights reserved.
Encoded novel forms of HSP70 or a cytolytic protein increase DNA vaccine potency.
Garrod, Tamsin; Grubor-Bauk, Branka; Yu, Stanley; Gargett, Tessa; Gowans, Eric J
2014-01-01
In humans, DNA vaccines have failed to demonstrate the equivalent levels of immunogenicity that were shown in smaller animals. Previous studies have encoded adjuvants, predominantly cytokines, within these vaccines in an attempt to increase antigen-specific immune responses. However, these strategies have lacked breadth of innate immune activation and have led to disappointing results in clinical trials. Damage associated molecular patterns (DAMPs) have been identified as pattern recognition receptor (PRR) agonists. DAMPs can bind to a wide range of PRRs on dendritic cells (DCs) and thus our studies have aimed to utilize this characteristic to act as an adjuvant in a DNA vaccine approach. Specifically, HSP70 has been identified as a DAMP, but has been limited by its lack of accessibility to PRRs in and on DCs. Here, we discuss the promising results achieved with the inclusion of membrane-bound or secreted HSP70 into a DNA vaccine encoding HIV gag as the model immunogen.
Golshani, Maryam; Rafati, Sima; Nejati-Moheimani, Mehdi; Ghasemian, Melina; Bouzari, Saeid
2016-12-25
In the present study, immunogenicity and protective efficacy of the Brucella outer membrane protein 2b (Omp2b) was evaluated in BALB/c mice using Protein/Protein, DNA/DNA and DNA/Protein vaccine strategies. Immunization of mice with three vaccine regimens elicited a strong specific IgG response (higher IgG2a titers over IgG1 titers) and provided Th1-oriented immune response. Vaccination of BALB/c mice with the DNA/Pro regimen induced higher levels of IFN-γ/IL-2 and conferred more protection levels against B. melitenisis and B. abortus challenge than did the protein or DNA alone. In conclusion, Omp2b is able to stimulate specific immune responses and to confer cross protection against B. melitensis and B. abortus infection. Therefore, it could be introduced as a new potential candidate for the development of a subunit vaccine against Brucella infection. Copyright © 2016 Elsevier B.V. All rights reserved.
Glycan bioengineering in immunogen design for tumor T antigen immunotargeting
DEFF Research Database (Denmark)
Sendra, Victor G; Zlocowski, Natacha; Ditamo, Yanina
2009-01-01
MM2 energy function showed that pentalysine (Lys5) linker and benzyl (Bzl) residue enhance TFD rigidity of the glycosidic bond. Antibodies raised against BzlalphaTFD-Lys5 immunogen recognize tumor T antigen. Competitive assays confirm that TFD-related structures are the main glycan epitope...... to the bioengineered glycoconjugate inhibited CT26 tumor cell proliferation and reduced tumor growth in an in vivo mouse model. These results show that TFD bioengineering is a useful immunogenic strategy with potential application in cancer therapy. The same approach can be extended to other glycan immunogens......Bioengineering of Galbeta3GalNAcalpha, known as Thomsen-Friedenreich disaccharide (TFD), is studied to promote glycan immunogenicity and immunotargeting to tumor T antigen (Galbeta3GalNAcalpha-O-Ser/Thr). Theoretical studies on disaccharide conformations by energy minimization of structures using...
Preclinical characterization and safety of a novel hydrogel for augmenting dural repair
International Nuclear Information System (INIS)
Strong, Michael J; Carnahan, Michael A; D’Alessio, Keith; Butlin, Jared D G; Butt, Mark T; Asher, Anthony L
2015-01-01
Cerebrospinal fluid (CSF) leakage is a potentially serious complication in surgical procedures involving opening of the dura mater. Although several materials have been developed to help achieve watertight dural closures, CSF leakages persist. The goal of this study was to evaluate the performance of a novel hydrogel designed to provide augmentation to standard methods of dural repair. Performance measures such as polymerization time, dimensional swelling, burst strength, and elasticity were examined in laboratory situations. Additionally, biocompatibility in an in vivo rat model was examined. The results demonstrate that this novel hydrogel has superior mechanical strength and tissue adherence with enhanced flexibility, reduced swelling, and quicker set time compared with existing hydrogel dural sealants approved for intra-cranial use. Furthermore, biocompatibility studies demonstrate that this compound is both non-toxic and non-immunogenic. (paper)
Phase 1 study of pandemic H1 DNA vaccine in healthy adults.
Directory of Open Access Journals (Sweden)
Michelle C Crank
Full Text Available A novel, swine-origin influenza A (H1N1 virus was detected worldwide in April 2009, and the World Health Organization (WHO declared a global pandemic that June. DNA vaccine priming improves responses to inactivated influenza vaccines. We describe the rapid production and clinical evaluation of a DNA vaccine encoding the hemagglutinin protein of the 2009 pandemic A/California/04/2009(H1N1 influenza virus, accomplished nearly two months faster than production of A/California/07/2009(H1N1 licensed monovalent inactivated vaccine (MIV.20 subjects received three H1 DNA vaccinations (4 mg intramuscularly with Biojector at 4-week intervals. Eighteen subjects received an optional boost when the licensed H1N1 MIV became available. The interval between the third H1 DNA injection and MIV boost was 3-17 weeks. Vaccine safety was assessed by clinical observation, laboratory parameters, and 7-day solicited reactogenicity. Antibody responses were assessed by ELISA, HAI and neutralization assays, and T cell responses by ELISpot and flow cytometry.Vaccinations were safe and well-tolerated. As evaluated by HAI, 6/20 developed positive responses at 4 weeks after third DNA injection and 13/18 at 4 weeks after MIV boost. Similar results were detected in neutralization assays. T cell responses were detected after DNA and MIV. The antibody responses were significantly amplified by the MIV boost, however, the boost did not increased T cell responses induced by DNA vaccine.H1 DNA vaccine was produced quickly, was well-tolerated, and had modest immunogenicity as a single agent. Other HA DNA prime-MIV boost regimens utilizing one DNA prime vaccination and longer boost intervals have shown significant immunogenicity. Rapid and large-scale production of HA DNA vaccines has the potential to contribute to an efficient response against future influenza pandemics.Clinicaltrials.gov NCT00973895.
Towards Pervasive Augmented Reality: Context-Awareness in Augmented Reality.
Grubert, Jens; Langlotz, Tobias; Zollmann, Stefanie; Regenbrecht, Holger
2017-06-01
Augmented Reality is a technique that enables users to interact with their physical environment through the overlay of digital information. While being researched for decades, more recently, Augmented Reality moved out of the research labs and into the field. While most of the applications are used sporadically and for one particular task only, current and future scenarios will provide a continuous and multi-purpose user experience. Therefore, in this paper, we present the concept of Pervasive Augmented Reality, aiming to provide such an experience by sensing the user's current context and adapting the AR system based on the changing requirements and constraints. We present a taxonomy for Pervasive Augmented Reality and context-aware Augmented Reality, which classifies context sources and context targets relevant for implementing such a context-aware, continuous Augmented Reality experience. We further summarize existing approaches that contribute towards Pervasive Augmented Reality. Based our taxonomy and survey, we identify challenges for future research directions in Pervasive Augmented Reality.
Salk's HIV immunogen: an immune-based therapy in human trials since 1988.
Jonas Salk, the developer of the first polio vaccine, has created a therapeutic vaccine for HIV which helps the immune system fight disease progression. Salk uses inactivated HIV-1 virus combined with Incomplete Freund's Adjuvant (IFA) in the vaccine preparation. The resulting HIV-1 immunogen was first studied in 1987, and since then, 235 seropositive individuals have received inoculations without serious adverse effects. Data from the first 25 subjects indicate that immunization with the HIV-1 immunogen results in improvement of cell-mediated response against the virus, a slower increase in the amount of virus present, and a reduced rate of clinical progression. Subsequent studies also show that higher doses of immunogen may produce stronger cell-mediated responses and high HIV-DTH (delayed-type hypersensitivity responsiveness immunogen) is associated with better outcome. Additional trials of HIV-1 immunogen are awaiting Food and Drug Administration approval.
Wikman, Maria; Friedman, Mikaela; Pinitkiatisakul, Sunan; Hemphill, Andrew; Lövgren-Bengtsson, Karin; Lundén, Anna; Ståhl, Stefan
2005-04-01
We have previously reported strategies for Escherichia coli production of recombinant immunogens fused to hydrophobic peptide or lipid tags to improve their capacity to be incorporated into an adjuvant formulation. In the present study, we have explored the strong interaction between biotin and SA (streptavidin) (K(D) approximately 10(-15) M) to couple recombinant immunogens to iscoms (immunostimulating complexes). Two different concepts were evaluated. In the first concept, a His(6)-tagged SA fusion protein (His(6)-SA) was bound to Ni(2+)-loaded iscom matrix (iscom without associated protein), and biotinylated immunogens were thereafter associated with the SA-coated iscoms. The immunogens were either biotinylated in vivo on E. coli expression or double biotinylated in vivo and in vitro. In the second concept, the recombinant immunogens were expressed as SA fusion proteins, which were directly bound to a biotinylated iscom matrix. A 53-amino-acid malaria peptide (M5), derived from the central repeat region of the Plasmodium falciparum blood-stage antigen Pf155/RESA, and a 232-amino-acid segment (SRS2') from the central region (from Pro-97 to Lys-328) of the major surface antigen NcSRS2 of the protozoan parasite Neospora caninum, served as model immunogens in the present study. All fusion proteins generated were found to be efficiently expressed and could be recovered to high purity using affinity chromatography. The association between the different immunogen-containing fusion proteins and the corresponding iscom matrix was demonstrated by analytical ultracentrifugation in a sucrose density gradient. However, some fusion proteins were, to a certain extent, also found to associate unspecifically with a regular iscom matrix. Furthermore, selected iscom fractions were demonstrated to induce high-titre antigen-specific antibody responses on immunization of mice. For the particular target immunogen SRS2', the induced antibodies demonstrated reactivity to the native
International Nuclear Information System (INIS)
Moser, E.
1992-01-01
During the past few years high rates of recidivation have increasingly been reported following drug treatment for hyperthyroidism. In view of these unsatisfactory results it is only natural that the use of surgery and ratioiodine treatment is now more often considered in order to achieve complete elimination of the metabolic disorders caused by hyperactivity of the thyroid gland. The aim of this study was to investigate into the effectiveness of radioiodine therapy in a large cohort of patients (n = 925). Particular attention was given to the influence of the dose applied to the thyroid tissue on the rates of success achieved in immunogenic hyperthyroidism (IH) and autonomous disorders (non-immunogenic hyperthyroidism = NIH). (orig./GDG) [de
Structure-Based Design of Head-Only Fusion Glycoprotein Immunogens for Respiratory Syncytial Virus.
Directory of Open Access Journals (Sweden)
Jeffrey C Boyington
Full Text Available Respiratory syncytial virus (RSV is a significant cause of severe respiratory illness worldwide, particularly in infants, young children, and the elderly. Although no licensed vaccine is currently available, an engineered version of the metastable RSV fusion (F surface glycoprotein-stabilized in the pre-fusion (pre-F conformation by "DS-Cav1" mutations-elicits high titer RSV-neutralizing responses. Moreover, pre-F-specific antibodies, often against the neutralization-sensitive antigenic site Ø in the membrane-distal head region of trimeric F glycoprotein, comprise a substantial portion of the human response to natural RSV infection. To focus the vaccine-elicited response to antigenic site Ø, we designed a series of RSV F immunogens that comprised the membrane-distal head of the F glycoprotein in its pre-F conformation. These "head-only" immunogens formed monomers, dimers, and trimers. Antigenic analysis revealed that a majority of the 70 engineered head-only immunogens displayed reactivity to site Ø-targeting antibodies, which was similar to that of the parent RSV F DS-Cav1 trimers, often with increased thermostability. We evaluated four of these head-only immunogens in detail, probing their recognition by antibodies, their physical stability, structure, and immunogenicity. When tested in naïve mice, a head-only trimer, half the size of the parent RSV F trimer, induced RSV titers, which were statistically comparable to those induced by DS-Cav1. When used to boost DS-Cav1-primed mice, two head-only RSV F immunogens, a dimer and a trimer, boosted RSV-neutralizing titers to levels that were comparable to those boosted by DS-Cav1, although with higher site Ø-directed responses. Our results provide proof-of-concept for the ability of the smaller head-only RSV F immunogens to focus the vaccine-elicited response to antigenic site Ø. Decent primary immunogenicity, enhanced physical stability, potential ease of manufacture, and potent
ARLearn: augmented reality meets augmented virtuality
Ternier, Stefaan; Klemke, Roland; Kalz, Marco; Van Ulzen, Patricia; Specht, Marcus
2012-01-01
Ternier, S., Klemke, R., Kalz, M., Van Ulzen, P., & Specht, M. (2012). ARLearn: augmented reality meets augmented virtuality [Special issue]. Journal of Universal Computer Science - Technology for learning across physical and virtual spaces, 18(15), 2143-2164.
Battlefield-Acquired Immunogenicity to Metals Affects Orthopaedic Implant Outcome
2015-10-01
Award Number: W81XWH-10-2-0138 TITLE: Battlefield-Acquired Immunogenicity to Metals Affects Orthopaedic Implant Outcome PRINCIPAL INVESTIGATOR...Immunogenicity to Metals Affects Orthopaedic pla t Outcome 5b. GRANT NUMBER W91ZSQ0135N646 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Nadim James...DISTRIBUTION / AVAILABILITY STATEMENT Approved for public release; distribution unlimited 13. SUPPLEM ENTARY NOTES 14. ABSTRACT The effects of battlefield
Understanding the immunogenicity and antigenicity of nanomaterials: Past, present and future
International Nuclear Information System (INIS)
Ilinskaya, Anna N.; Dobrovolskaia, Marina A.
2016-01-01
Nanoparticle immunogenicity and antigenicity have been under investigation for many years. During the past decade, significant progress has been made in understanding what makes a nanoparticle immunogenic, how immune cells respond to nanoparticles, what consequences of nanoparticle-specific antibody formation exist and how they challenge the application of nanoparticles for drug delivery. Moreover, it has been recognized that accidental contamination of therapeutic protein formulations with nanosized particulate materials may contribute to the immunogenicity of this type of biotechnology products. While the immunological properties of engineered nanomaterials and their application as vaccine carriers and adjuvants have been given substantial consideration in the current literature, little attention has been paid to nanoparticle immuno- and antigenicity. To fill in this gap, we herein provide an overview of this subject to highlight the current state of the field, review past and present research, and discuss future research directions. - Highlights: • Most engineered nanomaterials are not immunogenic per se. • Generation of nanoparticle-specific antibody can be T-cell dependent or independent. • Antibodies can be generated to particle core, terminal groups or surface coatings. • Engineered and accidental nanomaterials have distinct contribution to immunogenicity. • Tunable physicochemical properties make each nanoparticle unique.
Understanding the immunogenicity and antigenicity of nanomaterials: Past, present and future
Energy Technology Data Exchange (ETDEWEB)
Ilinskaya, Anna N.; Dobrovolskaia, Marina A., E-mail: marina@mail.nih.gov
2016-05-15
Nanoparticle immunogenicity and antigenicity have been under investigation for many years. During the past decade, significant progress has been made in understanding what makes a nanoparticle immunogenic, how immune cells respond to nanoparticles, what consequences of nanoparticle-specific antibody formation exist and how they challenge the application of nanoparticles for drug delivery. Moreover, it has been recognized that accidental contamination of therapeutic protein formulations with nanosized particulate materials may contribute to the immunogenicity of this type of biotechnology products. While the immunological properties of engineered nanomaterials and their application as vaccine carriers and adjuvants have been given substantial consideration in the current literature, little attention has been paid to nanoparticle immuno- and antigenicity. To fill in this gap, we herein provide an overview of this subject to highlight the current state of the field, review past and present research, and discuss future research directions. - Highlights: • Most engineered nanomaterials are not immunogenic per se. • Generation of nanoparticle-specific antibody can be T-cell dependent or independent. • Antibodies can be generated to particle core, terminal groups or surface coatings. • Engineered and accidental nanomaterials have distinct contribution to immunogenicity. • Tunable physicochemical properties make each nanoparticle unique.
Bernik , Aleš
2012-01-01
The aim of this thesis is the examination of augmented reality technology, which allows us mixing real and virtual elements. Augmented reality is a relatively new technology which is becoming more widespread, thanks to a fairly reasonable price of smart phones. Here we presents the types of augmented reality, the necessary technology and their advantages and disadvantages, its current use in applications, and software for building augmented reality applications. The thesis is mainly focuse...
Immunogenicity moderation effect of interleukin-24 on myelogenous leukemia cells.
Yu, Xin; Miao, Jingcheng; Xia, Wei; Gu, Zong-Jiang
2018-04-01
Previous studies have shown that interleukin-24 (IL-24) has tumor-suppressing activity by multiple pathways. However, the immunogenicity moderation effect of IL-24 on malignant cells has not been explored extensively. In this study, we investigated the role of IL-24 in immunogenicity modulation of the myelogenous leukemia cells. Data show that myelogenous leukemia cells express low levels of immunogenicity molecules. Treatment with IL-24 could enhance leukemia cell immunogenicity, predominantly regulate leukemia cells to produce immune-associated cytokines, and improve the cytotoxic sensitivity of these cells to immune effector cells. IL-24 expression could retard transplanted leukemia cell tumor growth in vivo in athymic nude mice. Moreover, IL-24 had marked effects on downregulating the expression of angiogenesis-related proteins vascular endothelial growth factor, cluster of differentiation (CD) 31, CD34, collagen IV and metastasis-related factors CD147, membrane type-1 matrix metalloproteinase (MMP), and MMP-2 and MMP-9 in transplanted tumors. These findings indicated novel functions of this antitumor gene and characterized IL-24 as a promising agent for further clinical trial for hematologic malignancy immunotherapy.
Viegas, Edna Omar; Tembe, Nelson; Nilsson, Charlotta; Meggi, Bindiya; Maueia, Cremildo; Augusto, Orvalho; Stout, Richard; Scarlatti, Gabriella; Ferrari, Guido; Earl, Patricia L; Wahren, Britta; Andersson, Sören; Robb, Merlin L; Osman, Nafissa; Biberfeld, Gunnel; Jani, Ilesh; Sandström, Eric
2017-11-27
We assessed the safety and immunogenicity of HIV-DNA priming using Zetajet™, a needle-free device intradermally followed by intramuscular HIV-MVA boosts, in 24 healthy Mozambicans. Volunteers were randomized to receive three immunizations of 600 μg (n = 10; 2 × 0.1 ml) or 1,200 μg (n = 10; 2 × 0.2 ml) of HIV-DNA (3 mg/ml), followed by two boosts of 10 8 pfu HIV-MVA. Four subjects received placebo saline injections. Vaccines and injections were safe and well tolerated with no difference between the two priming groups. After three HIV-DNA immunizations, IFN-γ ELISpot responses to Gag were detected in 9/17 (53%) vaccinees, while none responded to Envelope (Env). After the first HIV-MVA, the overall response rate to Gag and/or Env increased to 14/15 (93%); 14/15 (93%) to Gag and 13/15 (87%) to Env. There were no significant differences between the immunization groups in frequency of response to Gag and Env or magnitude of Gag responses. Env responses were significantly higher in the higher dose group (median 420 vs. 157.5 SFC/million peripheral blood mononuclear cell, p = .014). HIV-specific antibodies to subtype C gp140 and subtype B gp160 were elicited in all vaccinees after the second HIV-MVA, without differences in titers between the groups. Neutralizing antibody responses were not detected. Two (13%) of 16 vaccinees, one in each of the priming groups, exhibited antibodies mediating antibody-dependent cellular cytotoxicity to CRF01_AE. In conclusion, HIV-DNA vaccine delivered intradermally in volumes of 0.1-0.2 ml using Zetajet was safe and well tolerated. Priming with the 1,200 μg dose of HIV-DNA generated higher magnitudes of ELISpot responses to Env.
Stading, Benjamin; Osorio, Jorge E.; Velasco-Villa, Andres; Smotherman, Michael; Kingstad-Bakke, Brock; Rocke, Tonie E.
2016-01-01
Bats (Order Chiroptera) are an abundant group of mammals with tremendous ecological value as insectivores and plant dispersers, but their role as reservoirs of zoonotic diseases has received more attention in the last decade. With the goal of managing disease in free-ranging bats, we tested modified vaccinia Ankara (MVA) and raccoon poxvirus (RCN) as potential vaccine vectors in the Brazilian Free-tailed bat (Tadarida brasiliensis), using biophotonic in vivo imaging and immunogenicity studies. Animals were administered recombinant poxviral vectors expressing the luciferase gene (MVA-luc, RCN-luc) through oronasal (ON) or intramuscular (IM) routes and subsequently monitored for bioluminescent signal indicative of viral infection. No clinical illness was noted after exposure to any of the vectors, and limited luciferase expression was observed. Higher and longer levels of expression were observed with the RCN-luc construct. When given IM, luciferase expression was limited to the site of injection, while ON exposure led to initial expression in the oral cavity, often followed by secondary replication at another location, likely the gastric mucosa or gastric associated lymphatic tissue. Viral DNA was detected in oral swabs up to 7 and 9 days post infection (dpi) for MVA and RCN, respectively. While no live virus was detected in oral swabs from MVA-infected bats, titers up to 3.88 x 104 PFU/ml were recovered from oral swabs of RCN-infected bats. Viral DNA was also detected in fecal samples from two bats inoculated IM with RCN, but no live virus was recovered. Finally, we examined the immunogenicity of a RCN based rabies vaccine (RCN-G) following ON administration. Significant rabies neutralizing antibody titers were detected in the serum of immunized bats using the rapid fluorescence focus inhibition test (RFFIT). These studies highlight the safety and immunogenicity of attenuated poxviruses and their potential use as vaccine vectors in bats.
Immunogenicity of biotherapy used in psoriasis: the science behind the scenes.
Jullien, Denis; Prinz, Jörg C; Nestle, Frank O
2015-01-01
A potential limitation in the use of biologic drugs used to treat psoriasis is the development of anti-drug antibodies (ADAs). Many factors contribute to this unwanted immune response, from the product itself, to its mode of administration, the underlying disease, and patient characteristics. ADAs may decrease the efficacy of biologic drugs by neutralizing them or modifying their clearance and may account for hypersensitivity reactions. This article reviews the scientific basis of immunogenicity and the mechanisms by which it affects clinical outcomes. It also considers testing for immunogenicity and how biologic therapy of psoriasis may be tailored on the basis of immunogenicity.
International Nuclear Information System (INIS)
Ju, Huanyu; Wei, Na; Wang, Qian; Wang, Chunyuan; Jing, Zhiqiang; Guo, Lu; Liu, Dapeng; Gao, Mingchun; Ma, Bo; Wang, Junwei
2011-01-01
Highlights: → All three capsid proteins can be expressed in insect cells in baculovirus expression system. → All three recombinant proteins were spontaneously self-assemble into virus-like particles whose size and appearance were similar to those of native purified GPV virions. → The immunogenicity of GPV-VLPs was better than commercial inactivated vaccine and attenuated vaccine. -- Abstract: Goose parvovirus (GPV), a small non-enveloped ssDNA virus, can cause Derzsy's disease, and three capsid proteins of VP1, VP2, and VP3 are encoded by an overlapping nucleotide sequence. However, little is known on whether recombinant viral proteins (VPs) could spontaneously assemble into virus-like particles (VLPs) in insect cells and whether these VLPs could retain their immunoreactivity and immunogenicity in susceptible geese. To address these issues, genes for these GPV VPs were amplified by PCR, and the recombinant VPs proteins were expressed in insect cells using a baculovirus expression system for the characterization of their structures, immunoreactivity, and immunogenicity. The rVP1, rVP2, and rVP3 expressed in Sf9 cells were detected by anti-GPV sera, anti-VP3 sera, and anti-His antibodies, respectively. Electron microscopy revealed that these rVPs spontaneously assembled into VLPs in insect cells, similar to that of the purified wild-type GPV virions. In addition, vaccination with individual types of VLPs, particularly with the rVP2-VLPs, induced higher titers of antibodies and neutralized different strains of GPVs in primary goose and duck embryo fibroblast cells in vitro. These data indicated that these VLPs retained immunoreactivity and had strong immunogenicity in susceptible geese. Therefore, our findings may provide a framework for development of new vaccines for the prevention of Derzsy's disease and vehicles for the delivery of drugs.
Ruiz-Sternberg, Ángela María; Moreira, Edson D; Restrepo, Jaime A; Lazcano-Ponce, Eduardo; Cabello, Robinson; Silva, Arnaldo; Andrade, Rosires; Revollo, Francisco; Uscanga, Santos; Victoria, Alejandro; Guevara, Ana María; Luna, Joaquín; Plata, Manuel; Dominguez, Claudia Nossa; Fedrizzi, Edison; Suarez, Eugenio; Reina, Julio C; Ellison, Misoo C; Moeller, Erin; Ritter, Michael; Shields, Christine; Cashat, Miguel; Perez, Gonzalo; Luxembourg, Alain
2018-06-01
A 9-valent human papillomavirus (HPV6/11/16/18/31/33/45/52/58; 9vHPV) vaccine was developed to expand coverage of the previously developed quadrivalent (HPV6/11/16/18; qHPV) vaccine. Efficacy, immunogenicity, and safety outcomes were assessed in Latin American participants enrolled in 2 international studies of the 9vHPV vaccine, including a randomized, double-blinded, controlled with qHPV vaccine, efficacy, immunogenicity, and safety study in young women aged 16-26 years, and an immunogenicity and safety study in girls and boys aged 9-15 years. Participants (N=5312) received vaccination at Day 1, Month 2, and Month 6. Gynecological swabs were collected regularly in young women for cytological and HPV DNA testing. Serum was analyzed for HPV antibodies in all participants. Adverse events (AEs) were also monitored in all participants. The 9vHPV vaccine prevented HPV 31-, 33-, 45-, 52-, and 58-related high-grade cervical, vulvar, and vaginal dysplasia with 92.3% efficacy (95% confidence interval 54.4, 99.6). Anti-HPV6, 11, 16, and 18 geometric mean titers at Month 7 were similar in the 9vHPV and qHPV vaccination groups. Anti-HPV antibody responses following vaccination were higher among girls and boys than in young women. Most (>99%) 9vHPV vaccine recipients seroconverted for all 9 HPV types at Month 7. Antibody responses to the 9 HPV types persisted over 5 years. The most common AEs were injection-site related, mostly of mild to moderate intensity. The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Latin American young women, girls, and boys. These data support 9vHPV vaccination programs in Latin America, a region with substantial cervical cancer burden. Copyright © 2018 Merck Sharp & Dohme Corp., and The Authors. Published by Elsevier B.V. All rights reserved.
Energy Technology Data Exchange (ETDEWEB)
Ju, Huanyu; Wei, Na; Wang, Qian; Wang, Chunyuan; Jing, Zhiqiang; Guo, Lu; Liu, Dapeng; Gao, Mingchun; Ma, Bo [College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang 150030 (China); Wang, Junwei, E-mail: jwwang@neau.edu.cn [College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang 150030 (China)
2011-05-27
Highlights: {yields} All three capsid proteins can be expressed in insect cells in baculovirus expression system. {yields} All three recombinant proteins were spontaneously self-assemble into virus-like particles whose size and appearance were similar to those of native purified GPV virions. {yields} The immunogenicity of GPV-VLPs was better than commercial inactivated vaccine and attenuated vaccine. -- Abstract: Goose parvovirus (GPV), a small non-enveloped ssDNA virus, can cause Derzsy's disease, and three capsid proteins of VP1, VP2, and VP3 are encoded by an overlapping nucleotide sequence. However, little is known on whether recombinant viral proteins (VPs) could spontaneously assemble into virus-like particles (VLPs) in insect cells and whether these VLPs could retain their immunoreactivity and immunogenicity in susceptible geese. To address these issues, genes for these GPV VPs were amplified by PCR, and the recombinant VPs proteins were expressed in insect cells using a baculovirus expression system for the characterization of their structures, immunoreactivity, and immunogenicity. The rVP1, rVP2, and rVP3 expressed in Sf9 cells were detected by anti-GPV sera, anti-VP3 sera, and anti-His antibodies, respectively. Electron microscopy revealed that these rVPs spontaneously assembled into VLPs in insect cells, similar to that of the purified wild-type GPV virions. In addition, vaccination with individual types of VLPs, particularly with the rVP2-VLPs, induced higher titers of antibodies and neutralized different strains of GPVs in primary goose and duck embryo fibroblast cells in vitro. These data indicated that these VLPs retained immunoreactivity and had strong immunogenicity in susceptible geese. Therefore, our findings may provide a framework for development of new vaccines for the prevention of Derzsy's disease and vehicles for the delivery of drugs.
Liu, Betty R; Huang, Yue-Wern; Aronstam, Robert S; Lee, Han-Jung
2016-01-01
Cell-penetrating peptides (CPPs) have been shown to deliver cargos, including protein, DNA, RNA, and nanomaterials, in fully active forms into live cells. Most of the CPP sequences in use today are based on non-native proteins that may be immunogenic. Here we demonstrate that the L5a CPP (RRWQW) from bovine lactoferricin (LFcin), stably and noncovalently complexed with plasmid DNA and prepared at an optimal nitrogen/phosphate ratio of 12, is able to efficiently enter into human lung cancer A549 cells. The L5a CPP delivered a plasmid containing the enhanced green fluorescent protein (EGFP) coding sequence that was subsequently expressed in cells, as revealed by real-time PCR and fluorescent microscopy at the mRNA and protein levels, respectively. Treatment with calcium chloride increased the level of gene expression, without affecting CPP-mediated transfection efficiency. Zeta-potential analysis revealed that positively electrostatic interactions of CPP/DNA complexes correlated with CPP-mediated transport. The L5a and L5a/DNA complexes were not cytotoxic. This biomimetic LFcin L5a represents one of the shortest effective CPPs and could be a promising lead peptide with less immunogenic for DNA delivery in gene therapy.
Factors influencing preclinical in vivo evaluation of mumps vaccine strain immunogenicity.
Halassy, B; Kurtović, T; Brgles, M; Lang Balija, M; Forčić, D
2015-01-01
Immunogenicity testing in animals is a necessary preclinical assay for demonstration of vaccine efficacy the results of which are often the basis for the decision whether to proceed or withdraw the further development of the novel vaccine candidate. However, in vivo assays are rarely, if at all, optimized and validated. Here we clearly demonstrate the importance of in vivo assay (mumps virus immunogenicity testing in guinea pigs) optimization for gaining reliable results and the suitability of Fractional factorial design of experiments (DoE) for such a purpose. By the use of DoE with resolution IV (2IV((4-1))) we clearly revealed that the parameters significantly increasing assay sensitivity were interval between animal immunizations followed by the body weight of experimental animals. The quantity (0 versus 2%) of the stabilizer (fetal bovine serum, FBS) in the sample was shown as non-influencing parameter in DoE setup. However, the separate experiment investigating only the FBS influence, and performed under other parameters optimally set, showed that FBS also influences the results of immunogenicity assay. Such finding indicated that (a) factors with strong influence on the measured outcome can hide the effects of parameters with modest/low influence and (b) the matrix of mumps virus samples to be compared for immunogenicity must be identical for reliable virus immunogenicity comparison. Finally the 3 mumps vaccine strains widely used for decades in the licensed vaccines were for the first time compared in an animal model, and results obtained were in line with their reported immunogenicity in human population supporting the predictive power of the optimized in vivo assay.
Factors contributing to the immunogenicity of meningococcal conjugate vaccines
Bröker, Michael; Berti, Francesco; Costantino, Paolo
2016-01-01
ABSTRACT Various glycoprotein conjugate vaccines have been developed for the prevention of invasive meningococcal disease, having significant advantages over pure polysaccharide vaccines. One of the most important features of the conjugate vaccines is the induction of a T-cell dependent immune response, which enables both the induction of immune memory and a booster response after repeated immunization. The nature of the carrier protein to which the polysaccharides are chemically linked, is often regarded as the main component of the vaccine in determining its immunogenicity. However, other factors can have a significant impact on the vaccine's profile. In this review, we explore the physico-chemical properties of meningococcal conjugate vaccines, which can significantly contribute to the vaccine's immunogenicity. We demonstrate that the carrier is not the sole determining factor of the vaccine's profile, but, moreover, that the conjugate vaccine's immunogenicity is the result of multiple physico-chemical structures and characteristics. PMID:26934310
Immunogenicity of Anti-TNF-α Biotherapies
DEFF Research Database (Denmark)
Bendtzen, Klaus
2015-01-01
Immunogenicity of biopharmaceuticals is complex and influenced by both structural and pharmacological factors, and by patient-related conditions such as disease being treated, previous and concomitant therapies, and individual immune responsiveness. Essential for tailored therapeutic strategies b...
Ju, Huanyu; Wei, Na; Wang, Qian; Wang, Chunyuan; Jing, Zhiqiang; Guo, Lu; Liu, Dapeng; Gao, Mingchun; Ma, Bo; Wang, Junwei
2011-05-27
Goose parvovirus (GPV), a small non-enveloped ssDNA virus, can cause Derzsy's disease, and three capsid proteins of VP1, VP2, and VP3 are encoded by an overlapping nucleotide sequence. However, little is known on whether recombinant viral proteins (VPs) could spontaneously assemble into virus-like particles (VLPs) in insect cells and whether these VLPs could retain their immunoreactivity and immunogenicity in susceptible geese. To address these issues, genes for these GPV VPs were amplified by PCR, and the recombinant VPs proteins were expressed in insect cells using a baculovirus expression system for the characterization of their structures, immunoreactivity, and immunogenicity. The rVP1, rVP2, and rVP3 expressed in Sf9 cells were detected by anti-GPV sera, anti-VP3 sera, and anti-His antibodies, respectively. Electron microscopy revealed that these rVPs spontaneously assembled into VLPs in insect cells, similar to that of the purified wild-type GPV virions. In addition, vaccination with individual types of VLPs, particularly with the rVP2-VLPs, induced higher titers of antibodies and neutralized different strains of GPVs in primary goose and duck embryo fibroblast cells in vitro. These data indicated that these VLPs retained immunoreactivity and had strong immunogenicity in susceptible geese. Therefore, our findings may provide a framework for development of new vaccines for the prevention of Derzsy's disease and vehicles for the delivery of drugs. Copyright © 2011 Elsevier Inc. All rights reserved.
DEFF Research Database (Denmark)
Li, Yiping; Kang, H.N.; Babiuk, L.A.
2006-01-01
boosting with a recombinant E2 protein vaccine formulated with CpG ODN and 10% Emulsigen. The immunogenicity of HCV E2 vaccines was analyzed by ELISA for antibody responses, MTT assay for lymphocyte proliferation, ELISPOT for the number of interferon-gamma secreting cells, and cytotoxic T lymphocyte assays...... and shifted the immune response towards Th2-like ones in piglets. CONCLUSION: A DNA vaccine expressing a secreted form of HCV E2 protein elicited E2-specific immune responses in mice and piglets. Recombinant E2 protein vaccination following DNA immunization significantly increased the antibody response......AIM: To characterize the immunogenicity of a hepatitis C virus (HCV) E2 DNA vaccine alone or with a protein vaccine boost in murine and porcine animal models. METHODS: A DNA vaccine expressing a secreted form of HCV E2 protein was constructed and used to vaccinate mice and piglets with or without...
Fernández-Fernández, M Rosario; Martínez-Torrecuadrada, Jorge L; Roncal, Fernando; Domínguez, Elvira; García, Juan Antonio
2002-12-01
PEPSCAN analysis has been used to characterize the immunogenic regions of the capsid protein (CP) in virions of plum pox potyvirus (PPV). In addition to the well-known highly immunogenic N- and C-terminal domains of CP, regions within the core domain of the protein have also shown high immunogenicity. Moreover, the N terminus of CP is not homogeneously immunogenic, alternatively showing regions frequently recognized by antibodies and others that are not recognized at all. These results have helped us to design efficient antigen presentation vectors based on PPV. As predicted by PEPSCAN analysis, a small displacement of the insertion site in a previously constructed vector, PPV-gamma, turned the derived chimeras into efficient immunogens. Vectors expressing foreign peptides at different positions within a highly immunogenic region (amino acids 43 to 52) in the N-terminal domain of CP were the most effective at inducing specific antibody responses against the foreign sequence.
Directory of Open Access Journals (Sweden)
Anne Endmann
Full Text Available Currently marketed vaccines against hepatitis B virus (HBV based on the small (S hepatitis B surface antigen (HBsAg fail to induce a protective immune response in about 10% of vaccinees. DNA vaccination and the inclusion of PreS1 and PreS2 domains of HBsAg have been reported to represent feasible strategies to improve the efficacy of HBV vaccines. Here, we evaluated the immunogenicity of SAINT-18-formulated MIDGE-Th1 vectors encoding the S or the large (L protein of HBsAg in mice and pigs. In both animal models, vectors encoding the secretion-competent S protein induced stronger humoral responses than vectors encoding the L protein, which was shown to be retained mainly intracellularly despite the presence of a heterologous secretion signal. In pigs, SAINT-18-formulated MIDGE-Th1 vectors encoding the S protein elicited an immune response of the same magnitude as the licensed protein vaccine Engerix-B, with S protein-specific antibody levels significantly higher than those considered protective in humans, and lasting for at least six months after the third immunization. Thus, our results provide not only the proof of concept for the SAINT-18-formulated MIDGE-Th1 vector approach but also confirm that with a cationic-lipid formulation, a DNA vaccine at a relatively low dose can elicit an immune response similar to a human dose of an aluminum hydroxide-adjuvanted protein vaccine in large animals.
International Nuclear Information System (INIS)
Moser, E.; Pickardt, C.R.; Mann, K.; Engelhardt, D.; Kirsch, C.M.; Knesewitsch, P.; Tatsch, K.; Kreisig, T.; Kurz, C.; Saller, B.; Klinikum Grosshadern, Muenchen; Muenchen Univ.
1988-01-01
The aim of this study was to check the efficacy of radioiodine ( 131 I) therapy (RIT) in a large number of patients (n = 506) suffering from immunogenic or non-immunogenic hyperthyroidism (Graves' disease, Plummer's disease). Since there is no causal cure for immunogenic hyperthyroidism RIT provides, like all other modalities, only a moderate rate of success which is clearly dose-related. Applying 60 Gy, normal thyroid function can be achieved is only 54% of the cases. A dose of 150 Gy succeeds in 86% of the cases. The solitary decompensated autonomous adenoma (DAA) can be eliminated surgically as well as by RIT with a high degree of success (95%). Contrary to surgery, RIT does not have any noticeable early or late morbidity. The high rate of success of RIT in patients with DAA could be confirmed in two groups with different follow-up periods (16 and 65 months). As expected, the rate of hypothyroidism increased from 11% in the early group to 23% in the late group. Multinodular autonomous adenomas can be eliminated successfully using RIT as well. The concept to apply a dose of 400 Gy to the total functional autonomous tissue as determined by ultrasound yields better results (95%) than 150 Gy to the whole thyroid gland as measured by ultrasound (88%). The rate of hypothyroidism as shown by these results (up to a maximum of 62% after RIT of Graves' disease using 150 Gy) is the lesser evil compared to remaining or recurrent hyperthyroidism since these patients can be treated with thyroid hormones without problems. (orig.) [de
Hytti, Maria; Szabó, Dora; Piippo, Niina; Korhonen, Eveliina; Honkakoski, Paavo; Kaarniranta, Kai; Petrovski, Goran; Kauppinen, Anu
2017-04-01
Plant-derived polyphenols are known to possess anti-inflammatory and antioxidant effects. In recent years, several studies have investigated their potential benefits for treating chronic diseases associated with prolonged inflammation and excessive oxidative stress, such as age-related macular degeneration (AMD). Previously, two polyphenols, fisetin and luteolin, have been reported to increase the survival of retinal pigment epithelial (RPE) cells suffering from oxidative stress as well as decreasing inflammation but the benefits of polyphenol therapy seem to depend on the model system used. Our aim was to analyze the effects of fisetin and luteolin on inflammation and cellular viability in a model of nonoxidative DNA damage-induced cell death in human RPE (hRPE) cells. Pretreatment of ARPE-19 or primary hRPE cells with the polyphenols augmented etoposide-induced cell death as measured by the lactate dehydrogenase and 3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. However, the treatment was able to reduce the release of two proinflammatory cytokines, IL-6 and IL-8, which were determined by enzyme-linked Immunosorbent assay. Analyses of caspase 3 activity, p53 acetylation and SIRT1 protein levels revealed the apoptotic nature of etoposide-evoked cell death and that fisetin and luteolin augmented the etoposide-induced acetylation of p53 and decreased SIRT1 levels. Taken together, our findings suggest that the cytoprotective effects of fisetin and luteolin depend on the stressor they need to combat, whereas their anti-inflammatory potential is sustained over a variety of model systems. Careful consideration of disease pathways will be necessary before fisetin or luteolin can be recommended as therapeutic agents for inflammatory diseases in general and specifically AMD. Copyright © 2017 Elsevier Inc. All rights reserved.
DEFF Research Database (Denmark)
Rup, B; Pallardy, M; Sikkema, D
2015-01-01
scientists are involved in: interpretation and management of clinical and biological outcomes of BP immunogenicity, improvement of methods for describing, predicting and mitigating immunogenicity risk and elucidation of underlying causes. Collaboration and alignment of efforts across these communities...... the Risk; www.abirisk.eu] was formed by leading clinicians, academic scientists and EFPIA (European Federation of Pharmaceutical Industries and Associations) members to elucidate underlying causes, improve methods for immunogenicity prediction and mitigation and establish common definitions around terms...
Wang, Xing; Morgan, Donna M; Wang, Gan; Mozier, Ned M
2012-02-01
Residual DNA (rDNA) is comprised of deoxyribonucleic acid (DNA) fragments and longer length molecules originating from the host organism that may be present in samples from recombinant biological processes. Although similar in basic structural base pair units, rDNA may exist in different sizes and physical forms. Interest in measuring rDNA in recombinant products is based primarily on demonstration of effective purification during manufacturing, but also on some hypothetical concerns that, in rare cases, depending on the host expression system, some DNA sequences may be potentially infectious or oncogenic (e.g., HIV virus and the Ras oncogene, respectively). Recent studies suggest that a sequence known as long interspersed nucleotide element-1 (LINE-1), widely distributed in the mammalian genome, is active as a retrotransposon that can be transcribed to RNA, reverse-transcribed into DNA and inserts into a new site in genome. This integration process could potentially disrupt critical gene functions or induce tumorigenesis in mammals. Genomic DNA from microbial sources, on the other hand, could add to risk of immunogenicity to the target recombinant protein being expressed, due to the high CpG content and unmethylated DNA sequence. For these and other reasons, it is necessary for manufacturers to show clearance of DNA throughout production processes and to confirm low levels in the final drug substance using an appropriately specific and quantitative analytical method. The heterogeneity of potential rDNA sequences that might be makes the testing of all potential analytes challenging. The most common methodology for rDNA quantitation used currently is real-time polymerase chain reaction (RT-PCR), a robust and proven technology. Like most rDNA quantitation methods, the specificity of RT-PCR is limited by the sequences to which the primers are directed. To address this, primase-based whole genome amplification is introduced herein. This paper will review the recent
Charles-Niño, Claudia; Pedroza-Roldan, Cesar; Viveros, Monica; Gevorkian, Goar; Manoutcharian, Karen
2011-07-18
The extreme antigenic variability of human immunodeficiency virus (HIV) leads to immune escape of the virus, representing a major challenge in the design of effective vaccine. We have developed a novel concept for immunogen construction based on introduction of massive mutations within the epitopes targeting antigenically variable pathogens and diseases. Previously, we showed that these immunogens carrying large combinatorial libraries of mutated epitope variants, termed as variable epitope libraries (VELs), induce potent, broad and long lasting CD8+IFN-γ+ T-cell response. Moreover, we demonstrated that these T cells recognize more than 50% of heavily mutated variants (5 out of 10 amino acid positions were mutated in each epitope variant) of HIV-1 gp120 V3 loop-derived cytotoxic T lymphocyte epitope (RGPGRAFVTI) in mice. The constructed VELs had complexities of 10000 and 12500 individual members, generated as plasmid DNA or as M13 phage display combinatorial libraries, respectively, and with structural composition RGPGXAXXXX or XGXGXAXVXI, where X is any of 20 natural amino acids. Here, we demonstrated that sera from mice immunized with these VELs are capable of neutralizing 5 out of 10 viral isolates from Tier 2 reference panel of subtype B envelope clones, including HIV-1 isolates which are known to be resistant to neutralization by several potent monoclonal antibodies, described previously. These data indicate the feasibility of the application of immunogens based on VEL concept as an alternative approach for the development of molecular vaccines against antigenically variable pathogens. Copyright © 2011 Elsevier Ltd. All rights reserved.
Directory of Open Access Journals (Sweden)
Yingying Xu
2014-07-01
Full Text Available Intranasal delivery of DNA vaccines has become a popular research area recently. It offers some distinguished advantages over parenteral and other routes of vaccine administration. Nasal mucosa as site of vaccine administration can stimulate respiratory mucosal immunity by interacting with the nasopharyngeal-associated lymphoid tissues (NALT. Different kinds of DNA vaccines are investigated to provide protection against respiratory infectious diseases including tuberculosis, coronavirus, influenza and respiratory syncytial virus (RSV etc. DNA vaccines have several attractive development potential, such as producing cross-protection towards different virus subtypes, enabling the possibility of mass manufacture in a relatively short time and a better safety profile. The biggest obstacle to DNA vaccines is low immunogenicity. One of the approaches to enhance the efficacy of DNA vaccine is to improve DNA delivery efficiency. This review provides insight on the development of intranasal DNA vaccine for respiratory infections, with special attention paid to the strategies to improve the delivery of DNA vaccines using non-viral delivery agents.
Directory of Open Access Journals (Sweden)
Kar Muthumani
Full Text Available An effective HIV vaccine will most likely require the induction of strong T-cell responses, broadly neutralizing antibodies (bNAbs, and the elicitation of antibody-dependent cellular cytotoxicity (ADCC. Previously, we demonstrated the induction of strong HIV/SIV cellular immune responses in macaques and humans using synthetic consensus DNA immunogens delivered via adaptive electroporation (EP. However, the ability of this improved DNA approach to prime for relevant antibody responses has not been previously studied. Here, we investigate the immunogenicity of consensus DNA constructs encoding gp140 sequences from HIV-1 subtypes A, B, C and D in a DNA prime-protein boost vaccine regimen. Mice and guinea pigs were primed with single- and multi-clade DNA via EP and boosted with recombinant gp120 protein. Sera were analyzed for gp120 binding and induction of neutralizing antibody activity. Immunization with recombinant Env protein alone induced low-titer binding antibodies with limited neutralization breath. In contrast, the synthetic DNA prime-protein boost protocol induced significantly higher antibody binding titers. Furthermore, sera from DNA prime-protein boost groups were able to neutralize a broader range of viruses in a panel of tier 1 clade B viruses as well as multiple tier 1 clade A and clade C viruses. Further investigation of synthetic DNA prime plus adaptive EP plus protein boost appears warranted.
Sequence variability is correlated with weak immunogenicity in Streptococcus pyogenes M protein
Lannergård, Jonas; Kristensen, Bodil M; Gustafsson, Mattias C U; Persson, Jenny J; Norrby-Teglund, Anna; Stålhammar-Carlemalm, Margaretha; Lindahl, Gunnar
2015-01-01
The M protein of Streptococcus pyogenes, a major bacterial virulence factor, has an amino-terminal hypervariable region (HVR) that is a target for type-specific protective antibodies. Intriguingly, the HVR elicits a weak antibody response, indicating that it escapes host immunity by two mechanisms, sequence variability and weak immunogenicity. However, the properties influencing the immunogenicity of regions in an M protein remain poorly understood. Here, we studied the antibody response to different regions of the classical M1 and M5 proteins, in which not only the HVR but also the adjacent fibrinogen-binding B repeat region exhibits extensive sequence divergence. Analysis of antisera from S. pyogenes-infected patients, infected mice, and immunized mice showed that both the HVR and the B repeat region elicited weak antibody responses, while the conserved carboxy-terminal part was immunodominant. Thus, we identified a correlation between sequence variability and weak immunogenicity for M protein regions. A potential explanation for the weak immunogenicity was provided by the demonstration that protease digestion selectively eliminated the HVR-B part from whole M protein-expressing bacteria. These data support a coherent model, in which the entire variable HVR-B part evades antibody attack, not only by sequence variability but also by weak immunogenicity resulting from protease attack. PMID:26175306
Novel autoantigens immunogenic in COPD patients
Directory of Open Access Journals (Sweden)
Stephan Bernhard
2009-03-01
Full Text Available Abstract Background Chronic obstructive pulmonary disease (COPD is a respiratory inflammatory condition with autoimmune features including IgG autoantibodies. In this study we analyze the complexity of the autoantibody response and reveal the nature of the antigens that are recognized by autoantibodies in COPD patients. Methods An array of 1827 gridded immunogenic peptide clones was established and screened with 17 sera of COPD patients and 60 healthy controls. Protein arrays were evaluated both by visual inspection and a recently developed computer aided image analysis technique. By this computer aided image analysis technique we computed the intensity values for each peptide clone and each serum and calculated the area under the receiver operator characteristics curve (AUC for each clone and the separation COPD sera versus control sera. Results By visual evaluation we detected 381 peptide clones that reacted with autoantibodies of COPD patients including 17 clones that reacted with more than 60% of the COPD sera and seven clones that reacted with more than 90% of the COPD sera. The comparison of COPD sera and controls by the automated image analysis system identified 212 peptide clones with informative AUC values. By in silico sequence analysis we found an enrichment of sequence motives previously associated with immunogenicity. Conclusion The identification of a rather complex humoral immune response in COPD patients supports the idea of COPD as a disease with strong autoimmune features. The identification of novel immunogenic antigens is a first step towards a better understanding of the autoimmune component of COPD.
Arca, M J; Krauss, J C; Strome, S E; Cameron, M J; Chang, A E
1996-05-01
We evaluated the in vivo response to the poorly immunogenic B16-BL6 (BL6) murine melanoma genetically altered to secrete interleukin-2 (IL-2), IL-4, interferon gamma (IFN gamma) and granulocyte/macrophage-colony-stimulating factor (GM-CSF). Three parameters were evaluated: (1) tumorigenicity, (2) vaccination of naive animals, and (3) assessment of antitumor reactivity of T cells derived from tumor-draining lymph nodes (TDLN). Secretion of IL-2 abrogated the tumorigenicity of BL6, while IFN gamma and IL-4 partially reduced tumorigenicity, and GM-CSF had no effect. Protective immunity to wild-type tumor challenge could not be achieved by vaccination with irradiated cytokine-secreting tumors, although IL-2 and IL-4 secretion appeared to retard the growth of the challenge inoculum significantly. An alternative method to evaluate the immunogenicity of the cytokine-secreting tumors was to measure the ability of T cells obtained from TDLN to mediate regression of wild-type tumor in adoptive immunotherapy. Neither IL-2 nor IFN gamma secretion resulted in the induction of immune T cells. By contrast, GM-CSF and IL-4 secretion were found to induce immune T cells in the TDLN with GM-CSF being superior to IL-4. The combined secretion of GM-CSF and IL-4 did not lead to enhanced induction of immune T cells. GM-CSF secretion was found to upregulate B7-1 expression in TDLN, consistent with an increase in the population of antigen-presenting cells. These studies demonstrated that reduced tumorigenicity by cytokine secretion did not correlate with increased immunogenicity. With the cytokines examined, there was limited capability of developing protective immunity against the BL6 tumor. Nevertheless, GM-CSF and IL-4 secretion significantly enhanced T cell immune reactivity to the poorly immunogenic BL6 tumor.
Increase in DNA vaccine efficacy by virosome delivery and co-expression of a cytolytic protein.
Gargett, Tessa; Grubor-Bauk, Branka; Miller, Darren; Garrod, Tamsin; Yu, Stanley; Wesselingh, Steve; Suhrbier, Andreas; Gowans, Eric J
2014-06-01
The potential of DNA vaccines has not been realised due to suboptimal delivery, poor antigen expression and the lack of localised inflammation, essential for antigen presentation and an effective immune response to the immunogen. Initially, we examined the delivery of a DNA vaccine encoding a model antigen, luciferase (LUC), to the respiratory tract of mice by encapsulation in a virosome. Virosomes that incorporated influenza virus haemagglutinin effectively delivered DNA to cells in the mouse respiratory tract and resulted in antigen expression and systemic and mucosal immune responses to the immunogen after an intranasal (IN) prime/intradermal (ID) boost regimen, whereas a multidose ID regimen only generated systemic immunity. We also examined systemic immune responses to LUC after ID vaccination with a DNA vaccine, which also encoded one of the several cytolytic or toxic proteins. Although the herpes simplex virus thymidine kinase, in the presence of the prodrug, ganciclovir, resulted in cell death, this failed to increase the humoral or cell-mediated immune responses. In contrast, the co-expression of LUC with the rotavirus non-structural protein 4 (NSP4) protein or a mutant form of mouse perforin, proteins which are directly cytolytic, resulted in increased LUC-specific humoral and cell-mediated immunity. On the other hand, co-expression of LUC with diphtheria toxin subunit A or overexpression of perforin or NSP4 resulted in a lower level of immunity. In summary, the efficacy of DNA vaccines can be improved by targeted IN delivery of DNA or by the induction of cell death in vaccine-targeted cells after ID delivery.
Ledgerwood, J E; Costner, P; Desai, N; Holman, L; Enama, M E; Yamshchikov, G; Mulangu, S; Hu, Z; Andrews, C A; Sheets, R A; Koup, R A; Roederer, M; Bailer, R; Mascola, J R; Pau, M G; Sullivan, N J; Goudsmit, J; Nabel, G J; Graham, B S
2010-12-16
Ebola virus causes irregular outbreaks of severe hemorrhagic fever in equatorial Africa. Case mortality remains high; there is no effective treatment and outbreaks are sporadic and unpredictable. Studies of Ebola virus vaccine platforms in non-human primates have established that the induction of protective immunity is possible and safety and human immunogenicity has been demonstrated in a previous Phase I clinical trial of a 1st generation Ebola DNA vaccine. We now report the safety and immunogenicity of a recombinant adenovirus serotype 5 (rAd5) vaccine encoding the envelope glycoprotein (GP) from the Zaire and Sudan Ebola virus species, in a randomized, placebo-controlled, double-blinded, dose escalation, Phase I human study. Thirty-one healthy adults received vaccine at 2×10(9) (n=12), or 2×10(10) (n=11) viral particles or placebo (n=8) as an intramuscular injection. Antibody responses were assessed by ELISA and neutralizing assays; and T cell responses were assessed by ELISpot and intracellular cytokine staining assays. This recombinant Ebola virus vaccine was safe and subjects developed antigen specific humoral and cellular immune responses. Published by Elsevier Ltd.
Immunogenicity and Clinical Efficacy of Influenza Vaccination In Pregnancy
Directory of Open Access Journals (Sweden)
Alexander W Kay
2015-06-01
Full Text Available Pregnant women are at high risk from influenza due to disproportionate morbidity, mortality, and adverse pregnancy outcomes following infection. As such, they are classified as a high priority group for vaccination. However, changes in the maternal immune system required to accommodate the allogeneic fetus may alter the immunogenicity of influenza vaccines. A large number of studies have evaluated the safety of the influenza vaccine. Here, we will review available studies on the immunogenicity and efficacy of the influenza vaccine during pregnancy, focusing on both humoral and cellular immunity.
Directory of Open Access Journals (Sweden)
Betty R Liu
Full Text Available Cell-penetrating peptides (CPPs have been shown to deliver cargos, including protein, DNA, RNA, and nanomaterials, in fully active forms into live cells. Most of the CPP sequences in use today are based on non-native proteins that may be immunogenic. Here we demonstrate that the L5a CPP (RRWQW from bovine lactoferricin (LFcin, stably and noncovalently complexed with plasmid DNA and prepared at an optimal nitrogen/phosphate ratio of 12, is able to efficiently enter into human lung cancer A549 cells. The L5a CPP delivered a plasmid containing the enhanced green fluorescent protein (EGFP coding sequence that was subsequently expressed in cells, as revealed by real-time PCR and fluorescent microscopy at the mRNA and protein levels, respectively. Treatment with calcium chloride increased the level of gene expression, without affecting CPP-mediated transfection efficiency. Zeta-potential analysis revealed that positively electrostatic interactions of CPP/DNA complexes correlated with CPP-mediated transport. The L5a and L5a/DNA complexes were not cytotoxic. This biomimetic LFcin L5a represents one of the shortest effective CPPs and could be a promising lead peptide with less immunogenic for DNA delivery in gene therapy.
Intrinsic immunogenicity of rapidly-degradable polymers evolves during degradation.
Andorko, James I; Hess, Krystina L; Pineault, Kevin G; Jewell, Christopher M
2016-03-01
Recent studies reveal many biomaterial vaccine carriers are able to activate immunostimulatory pathways, even in the absence of other immune signals. How the changing properties of polymers during biodegradation impact this intrinsic immunogenicity is not well studied, yet this information could contribute to rational design of degradable vaccine carriers that help direct immune response. We use degradable poly(beta-amino esters) (PBAEs) to explore intrinsic immunogenicity as a function of the degree of polymer degradation and polymer form (e.g., soluble, particles). PBAE particles condensed by electrostatic interaction to mimic a common vaccine approach strongly activate dendritic cells, drive antigen presentation, and enhance T cell proliferation in the presence of antigen. Polymer molecular weight strongly influences these effects, with maximum stimulation at short degradation times--corresponding to high molecular weight--and waning levels as degradation continues. In contrast, free polymer is immunologically inert. In mice, PBAE particles increase the numbers and activation state of cells in lymph nodes. Mechanistic studies reveal that this evolving immunogenicity occurs as the physicochemical properties and concentration of particles change during polymer degradation. This work confirms the immunological profile of degradable, synthetic polymers can evolve over time and creates an opportunity to leverage this feature in new vaccines. Degradable polymers are increasingly important in vaccination, but how the inherent immunogenicity of polymers changes during degradation is poorly understood. Using common rapidly-degradable vaccine carriers, we show that the activation of immune cells--even in the absence of other adjuvants--depends on polymer form (e.g., free, particulate) and the extent of degradation. These changing characteristics alter the physicochemical properties (e.g., charge, size, molecular weight) of polymer particles, driving changes in
Generation and Characterization of a Defective HIV-1 Virus as an Immunogen for a Therapeutic Vaccine
García-Pérez, Javier; García, Felipe; Blanco, Julia; Escribà-García, Laura; Gatell, Jose Maria; Alcamí, Jose; Plana, Montserrat; Sánchez-Palomino, Sonsoles
2012-01-01
Background The generation of new immunogens able to elicit strong specific immune responses remains a major challenge in the attempts to obtain a prophylactic or therapeutic vaccine against HIV/AIDS. We designed and constructed a defective recombinant virus based on the HIV-1 genome generating infective but non-replicative virions able to elicit broad and strong cellular immune responses in HIV-1 seropositive individuals. Results Viral particles were generated through transient transfection in producer cells (293-T) of a full length HIV-1 DNA carrying a deletion of 892 base pairs (bp) in the pol gene encompassing the sequence that codes for the reverse transcriptase (NL4-3/ΔRT clone). The viral particles generated were able to enter target cells, but due to the absence of reverse transcriptase no replication was detected. The immunogenic capacity of these particles was assessed by ELISPOT to determine γ-interferon production in a cohort of 69 chronic asymptomatic HIV-1 seropositive individuals. Surprisingly, defective particles produced from NL4-3/ΔRT triggered stronger cellular responses than wild-type HIV-1 viruses inactivated with Aldrithiol-2 (AT-2) and in a larger proportion of individuals (55% versus 23% seropositive individuals tested). Electron microscopy showed that NL4-3/ΔRT virions display immature morphology. Interestingly, wild-type viruses treated with Amprenavir (APV) to induce defective core maturation also induced stronger responses than the same viral particles generated in the absence of protease inhibitors. Conclusions We propose that immature HIV-1 virions generated from NL4-3/ΔRT viral clones may represent new prototypes of immunogens with a safer profile and stronger capacity to induce cellular immune responses than wild-type inactivated viral particles. PMID:23144996
Characterization of a linear epitope on Chlamydia trachomatis serovar L2 DnaK-like protein
DEFF Research Database (Denmark)
Ozkokmen, D; Birkelund, Svend; Christiansen, Gunna
1994-01-01
A cytoplasmic 75-kDa immunogen from Chlamydia trachomatis serovar L2 has previously been characterized as being similar to the Escherichia coli heat shock protein DnaK. We have localized a linear epitope for one monoclonal antibody specific for C. trachomatis DnaK. By use of a recombinant DNA...... technique, the epitope was limited to 14 amino acids. With synthetic peptides, the epitope was further limited to eight amino acids. Six of these amino acids are conserved in bovine HSP70, which has a known three-dimensional structure. The amino acid sequence homologous to the epitope is located in a linear...
Secondary Breast Augmentation.
Brown, Mitchell H; Somogyi, Ron B; Aggarwal, Shagun
2016-07-01
After studying this article, the participant should be able to: 1. Assess common clinical problems in the secondary breast augmentation patient. 2. Describe a treatment plan to correct the most common complications of breast augmentation. 3. Provide surgical and nonsurgical options for managing complications of breast augmentation. 4. Decrease the incidence of future complications through accurate assessment, preoperative planning, and precise surgical technique. Breast augmentation has been increasing steadily in popularity over the past three decades. Many of these patients present with secondary problems or complications following their primary breast augmentation. Two of the most common complications are capsular contracture and implant malposition. Familiarity and comfort with the assessment and management of these complications is necessary for all plastic surgeons. An up-to-date understanding of current devices and techniques may decrease the need to manage future complications from the current cohort of breast augmentation patients.
ChemPreview: an augmented reality-based molecular interface.
Zheng, Min; Waller, Mark P
2017-05-01
Human computer interfaces make computational science more comprehensible and impactful. Complex 3D structures such as proteins or DNA are magnified by digital representations and displayed on two-dimensional monitors. Augmented reality has recently opened another door to access the virtual three-dimensional world. Herein, we present an augmented reality application called ChemPreview with the potential to manipulate bio-molecular structures at an atomistic level. ChemPreview is available at https://github.com/wallerlab/chem-preview/releases, and is built on top of the Meta 1 platform https://www.metavision.com/. ChemPreview can be used to interact with a protein in an intuitive way using natural hand gestures, thereby making it appealing to computational chemists or structural biologists. The ability to manipulate atoms in real world could eventually provide new and more efficient ways of extracting structural knowledge, or designing new molecules in silico. Copyright © 2017 Elsevier Inc. All rights reserved.
International Nuclear Information System (INIS)
Kim, Eun-Sung; Yang, Seung-Woo; Hong, Dong-Ki; Kim, Woo-Taek; Kim, Ho-Guen; Lee, Sang-Kyou
2010-01-01
Non-viral gene delivery is a safe and suitable alternative to viral vector-mediated delivery to overcome the immunogenicity and tumorigenesis associated with viral vectors. Using the novel, human-origin Hph-1 protein transduction domain that can facilitate the transduction of protein into cells, we developed a new strategy to deliver naked DNA in vitro and in vivo. The new DNA delivery system contains Hph-1-GAL4 DNA-binding domain (DBD) fusion protein and enhanced green fluorescent protein (EGFP) reporter plasmid that includes the five repeats of GAL4 upstream activating sequence (UAS). Hph-1-GAL4-DBD protein formed complex with plasmid DNA through the specific interaction between GAL4-DBD and UAS, and delivered into the cells via the Hph-1-PTD. The pEGFP DNA was successfully delivered by the Hph-1-GAL4 system, and the EGFP was effectively expressed in mammalian cells such as HeLa and Jurkat, as well as in Bright Yellow-2 (BY-2) plant cells. When 10 μg of pEGFP DNA was intranasally administered to mice using Hph-1-GAL4 protein, a high level of EGFP expression was detected throughout the lung tissue for 7 days. These results suggest that an Hph-1-PTD-mediated DNA delivery strategy may be an useful non-viral DNA delivery system for gene therapy and DNA vaccines.
Energy Technology Data Exchange (ETDEWEB)
Kim, Eun-Sung; Yang, Seung-Woo [Department of Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Hong, Dong-Ki; Kim, Woo-Taek [Department of Biology, Yonsei University, Seoul 120-749 (Korea, Republic of); Kim, Ho-Guen [Department of Pathology, Yonsei Medical School, Seoul 120-752 (Korea, Republic of); Lee, Sang-Kyou, E-mail: sjrlee@yonsei.ac.kr [Department of Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)
2010-01-29
Non-viral gene delivery is a safe and suitable alternative to viral vector-mediated delivery to overcome the immunogenicity and tumorigenesis associated with viral vectors. Using the novel, human-origin Hph-1 protein transduction domain that can facilitate the transduction of protein into cells, we developed a new strategy to deliver naked DNA in vitro and in vivo. The new DNA delivery system contains Hph-1-GAL4 DNA-binding domain (DBD) fusion protein and enhanced green fluorescent protein (EGFP) reporter plasmid that includes the five repeats of GAL4 upstream activating sequence (UAS). Hph-1-GAL4-DBD protein formed complex with plasmid DNA through the specific interaction between GAL4-DBD and UAS, and delivered into the cells via the Hph-1-PTD. The pEGFP DNA was successfully delivered by the Hph-1-GAL4 system, and the EGFP was effectively expressed in mammalian cells such as HeLa and Jurkat, as well as in Bright Yellow-2 (BY-2) plant cells. When 10 {mu}g of pEGFP DNA was intranasally administered to mice using Hph-1-GAL4 protein, a high level of EGFP expression was detected throughout the lung tissue for 7 days. These results suggest that an Hph-1-PTD-mediated DNA delivery strategy may be an useful non-viral DNA delivery system for gene therapy and DNA vaccines.
DEFF Research Database (Denmark)
Beekman, N.J.C.M.; Schaaper, W.M.M.; Tesser, G.I.
1997-01-01
Synthetic peptides have frequently been used to immunize animals. However, peptides less than about 20 to 30 amino acids long are poor immunogens. In general, to increase its immunogenicity, the presentation of the peptide should be improved, and molecular weight needs to be increased. Many...... or an amide bond. It was found that these S-palmitoylated peptides were much more immunogenic than N-palmitoylated peptides and at least similar to KLH-conjugated peptides with respect to appearance and magnitude of induced antibodies (canine parvovirus) or immunocastration effect (gonadotropin...
Sequence variability is correlated with weak immunogenicity in Streptococcus pyogenes M protein.
Lannergård, Jonas; Kristensen, Bodil M; Gustafsson, Mattias C U; Persson, Jenny J; Norrby-Teglund, Anna; Stålhammar-Carlemalm, Margaretha; Lindahl, Gunnar
2015-10-01
The M protein of Streptococcus pyogenes, a major bacterial virulence factor, has an amino-terminal hypervariable region (HVR) that is a target for type-specific protective antibodies. Intriguingly, the HVR elicits a weak antibody response, indicating that it escapes host immunity by two mechanisms, sequence variability and weak immunogenicity. However, the properties influencing the immunogenicity of regions in an M protein remain poorly understood. Here, we studied the antibody response to different regions of the classical M1 and M5 proteins, in which not only the HVR but also the adjacent fibrinogen-binding B repeat region exhibits extensive sequence divergence. Analysis of antisera from S. pyogenes-infected patients, infected mice, and immunized mice showed that both the HVR and the B repeat region elicited weak antibody responses, while the conserved carboxy-terminal part was immunodominant. Thus, we identified a correlation between sequence variability and weak immunogenicity for M protein regions. A potential explanation for the weak immunogenicity was provided by the demonstration that protease digestion selectively eliminated the HVR-B part from whole M protein-expressing bacteria. These data support a coherent model, in which the entire variable HVR-B part evades antibody attack, not only by sequence variability but also by weak immunogenicity resulting from protease attack. © 2015 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.
Directory of Open Access Journals (Sweden)
Ángela María Ruiz-Sternberg
2018-06-01
Full Text Available Background: A 9-valent human papillomavirus (HPV6/11/16/18/31/33/45/52/58; 9vHPV vaccine was developed to expand coverage of the previously developed quadrivalent (HPV6/11/16/18; qHPV vaccine. Methods: Efficacy, immunogenicity, and safety outcomes were assessed in Latin American participants enrolled in 2 international studies of the 9vHPV vaccine, including a randomized, double-blinded, controlled with qHPV vaccine, efficacy, immunogenicity, and safety study in young women aged 16–26 years, and an immunogenicity and safety study in girls and boys aged 9–15 years. Participants (N=5312 received vaccination at Day 1, Month 2, and Month 6. Gynecological swabs were collected regularly in young women for cytological and HPV DNA testing. Serum was analyzed for HPV antibodies in all participants. Adverse events (AEs were also monitored in all participants. Results: The 9vHPV vaccine prevented HPV 31-, 33-, 45-, 52-, and 58-related high-grade cervical, vulvar, and vaginal dysplasia with 92.3% efficacy (95% confidence interval 54.4, 99.6. Anti-HPV6, 11, 16, and 18 geometric mean titers at Month 7 were similar in the 9vHPV and qHPV vaccination groups. Anti-HPV antibody responses following vaccination were higher among girls and boys than in young women. Most (>99% 9vHPV vaccine recipients seroconverted for all 9 HPV types at Month 7. Antibody responses to the 9 HPV types persisted over 5 years. The most common AEs were injection-site related, mostly of mild to moderate intensity. Conclusions: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Latin American young women, girls, and boys. These data support 9vHPV vaccination programs in Latin America, a region with substantial cervical cancer burden. Keywords: Human papillomavirus, Vaccine, Cervical cancer, Persistent infection, 9vHPV
Enhancing poxvirus vectors vaccine immunogenicity.
García-Arriaza, Juan; Esteban, Mariano
2014-01-01
Attenuated recombinant poxvirus vectors expressing heterologous antigens from pathogens are currently at various stages in clinical trials with the aim to establish their efficacy. This is because these vectors have shown excellent safety profiles, significant immunogenicity against foreign expressed antigens and are able to induce protective immune responses. In view of the limited efficacy triggered by some poxvirus strains used in clinical trials (i.e, ALVAC in the RV144 phase III clinical trial for HIV), and of the restrictive replication capacity of the highly attenuated vectors like MVA and NYVAC, there is a consensus that further improvements of these vectors should be pursuit. In this review we considered several strategies that are currently being implemented, as well as new approaches, to improve the immunogenicity of the poxvirus vectors. This includes heterologous prime/boost protocols, use of co-stimulatory molecules, deletion of viral immunomodulatory genes still present in the poxvirus genome, enhancing virus promoter strength, enhancing vector replication capacity, optimizing expression of foreign heterologous sequences, and the combined use of adjuvants. An optimized poxvirus vector triggering long-lasting immunity with a high protective efficacy against a selective disease should be sought.
Ma, Yan-Ping; Ke, Hao; Liang, Zhi-Ling; Ma, Jiang-Yao; Hao, Le; Liu, Zhen-Xing
2017-07-01
Streptococcus agalactiae (S. agalactiae) is an important fish pathogen, which has received more attention in the past decade due to the increasing economic losses in the tilapia industry worldwide. As existing effective vaccines of S. agalactiae in fish have obvious disadvantage, to select immunoprotective antigens and package materials would undoubtedly contribute to the development of novel oral vaccines. In the present study, surface immunogenic protein (sip) was selected from the S. agalactiae serovar I a genomes as immunogenic protein in DNA vaccine form with cationic chitosan and biodegradable and biocompatible PLGA. The pcSip plasmid in cationic-PLGA was successfully expressed in tissues of immunized tilapia and the immunogenicity was assessed in tilapia challenge model. A significant increase was observed in the cytokine levels of IL-1β, TNF-α, CC1, CC2 in spleen and kidney tissues. Furthermore, immunized tilapia conferred different levels of protection against challenge with a lethal dose of highly virulent serovar I a S. agalactiae. Our results indicated that the pcSip plasmid in cationic-PLGA induced high level of antibodies and protection against S. agalactiae infection, could be effective oral DNA vaccine candidates. Copyright © 2017 Elsevier Ltd. All rights reserved.
Subhani, Zuhaib; Daniel, Barbara; Frascione, Nunzianda
2018-05-25
This study evaluated the compatibility of the most common enhancement methods and lifting techniques with DNA profiling. Emphasis is placed on modern lifting techniques (i.e., gelatin lifters and Isomark™) and historical fingerprint lifts for which limited research has been previously conducted. A total of 180 fingerprints were deposited on a glass surface, enhanced, lifted, and processed for DNA typing. DNA could be extracted and profiled for all the powders and lifts tested and from both groomed fingerprints and natural prints with no significant difference in the percentage of profile recovered. DNA profiles could also be obtained from historical fingerprint lifts (79.2% of 72 lifts) with one or more alleles detected. These results demonstrate the compatibility between different powder/lift combinations and DNA profiling therefore augmenting the evidential value of fingerprints in forensic casework. © 2018 American Academy of Forensic Sciences.
Miandare, Hamed Kolangi; Mirghaed, Ali Taheri; Hosseini, Marjan; Mazloumi, Nastaran; Zargar, Ashkan; Nazari, Sajad
2017-11-01
Pacific white shrimp Litopenaeus vannamei (Boone, 1931) is an important economical shrimp species worldwide, especially in the Middle East region, and farming activities of this species have been largely affected by diseases, mostly viral and bacterial diseases. Scientists have started to use prebiotics for bolstering the immune status of the animal. This study aimed to investigate the influence of Immunogen ® on growth, digestive enzyme activity and immune related gene expression of Litopenaeus vannamei post-larvae. All post-larvae were acclimated to the laboratory condition for 14 days. Upon acclimation, shrimps were fed on different levels of Immunogen ® (0, 0.5, 1 and 1.5 g kg -1 ) for 60 days. No significant differences were detected in weight gain, specific growth rate (SGR) and food conversion ratio (FCR) in shrimp post-larvae in which fed with different levels of Immunogen ® and control diet. The results showed that digestive enzymes activity including protease and lipase increased with different amounts of Immunogen ® in the shrimp diet. Protease activity increased with 1.5 g kg -1 Immunogen ® after 60 days and lipase activity increased with 1 and 1.5 g kg -1 Immunogen ® after 30 and 60 days of the trial respectively (P 0.05). The expression of immune related genes including, prophenoloxidase, crustin and g-type lysozyme increased with diet 1.5 g kg -1 Immunogen ® (P < 0.05) while expression of penaeidin gene increased only with experimental diet 1 g kg -1 of Immunogen ® . These results indicated that increase in digestive enzymes activity and expression of immune related genes could modulate the Immunogen ® in the innate immune system in L. vannamei in this study. Copyright © 2017. Published by Elsevier Ltd.
Efficacy of a DNA Vaccine Carrying Eimeria maxima Gam56 Antigen Gene against Coccidiosis in Chickens
Xu, Jinjun; Zhang, Yan
2013-01-01
To control coccidiosis without using prophylactic medications, a DNA vaccine targeting the gametophyte antigen Gam56 from Eimeria maxima in chickens was constructed, and the immunogenicity and protective effects were evaluated. The ORF of Gam56 gene was cloned into an eukaryotic expression vector pcDNA3.1(zeo)+. Expression of Gam56 protein in COS-7 cells transfected with recombinant plasmid pcDNA-Gam56 was confirmed by indirect immunofluorescence assay. The DNA vaccine was injected intramuscularly to yellow feathered broilers of 1-week old at 3 dosages (25, 50, and 100 µg/chick). Injection was repeated once 1 week later. One week after the second injection, birds were challenged orally with 5×104 sporulated oocysts of E. maxima, then weighed and killed at day 8 post challenge. Blood samples were collected and examined for specific peripheral blood lymphocyte proliferation activity and serum antibody levels. Compared with control groups, the administration of pcDNA-Gam56 vaccine markedly increased the lymphocyte proliferation activity (P<0.05) at day 7 and 14 after the first immunization. The level of lymphocyte proliferation started to decrease on day 21 after the first immunization. A similar trend was seen in specific antibody levels. Among the 3 pcDNA-Gam56 immunized groups, the median dosage group displayed the highest lymphocyte proliferation and antibody levels (P<0.05). The median dosage group had the greatest relative body weight gain (89.7%), and the greatest oocyst shedding reduction (53.7%). These results indicate that median dosage of DNA vaccine had good immunogenicity and immune protection effects, and may be used in field applications for coccidiosis control. PMID:23710081
Directory of Open Access Journals (Sweden)
Patrik Pucer
2011-08-01
Full Text Available Today we can obtain in a simple and rapid way most of the information that we need. Devices, such as personal computers and mobile phones, enable access to information in different formats (written, pictorial, audio or video whenever and wherever. Daily we use and encounter information that can be seen as virtual objects or objects that are part of the virtual world of computers. Everyone, at least once, wanted to bring these virtual objects from the virtual world of computers into real environments and thus mix virtual and real worlds. In such a mixed reality, real and virtual objects coexist in the same environment. The reality, where users watch and use the real environment upgraded with virtual objects is called augmented reality. In this article we describe the main properties of augmented reality. In addition to the basic properties that define a reality as augmented reality, we present the various building elements (possible hardware and software that provide an insight into such a reality and practical applications of augmented reality. The applications are divided into three groups depending on the information and functions that augmented reality offers, such as help, guide and simulator.
Directory of Open Access Journals (Sweden)
A.N. Mironov
2010-01-01
Full Text Available NPO «Microgen» developed vaccine «PANDEFLU» — influenza inactivated subunit adsorbed monovalent vaccine, strain A/California/7/2009 (H1N1, for specific prophylaxis of pandemic influenza in different age groups of citizens. Reactogenicity, safety and immunogenicity were analyzed in a study of volunteers 18–60 years old. The article presents results of administration of vaccine «PANDEFLU» in children. The study performed in two clinical centers proves good tolerability, reactogenicity, safety and high immunogenicity of this vaccine.Key words: children, influenza, influenza virus А/H1N1, inactivated influenza vaccine, reactogenicity, safety, immunogenicity.(Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(4:106-109
International Nuclear Information System (INIS)
Eisenberg, G.H. Jr.; Osterman, J.V.
1979-01-01
Scrub typhus immunogens were prepared from Rickettsia tsutsugamushi strains Karp, Kato, Gilliam, Kostival, and Buie by exposing frozen infected yolk sac suspensions to 300 krad of gamma radiation. Mouse protection tests showed that each of the irradiated immunogens protected C3H/HeDub mice against high challenge levels of Karp and Gilliam, but that none of these single-strain immunogens were capable of protecting against all five of the challenge strains. Broad-spectrum protection was achieved by using combinations of three strains of irradiated rickettsiae in a vaccination regimen of three injections at 5-day intervals
International Nuclear Information System (INIS)
Lafer, E.M.; Moeller, A.; Valle, R.P.C.; Nordheim, V.A.; Rich, A.; Stollar, B.D.; Massachusetts Inst. of Tech., Cambridge)
1983-01-01
To measure serological reactions under physiological ionic strength, we prepared a brominated (Bl) poly(dG-dC).poly(dG-dC), which forms a stable Z helix in solutions of low salt concentration. Mice and rabbits were immunized with this polymer complexed with the basic protein methylated bovine serum albumin (MBSA), and it was discovered that the Z-DNA helix is a strong immunogen. Various antibody populations were purified from the rabbit serum by quantitative immunoprecipitation. Spleen cells from the mice were used for the preparation of hybridoma cell lines secreting monoclonal antibodies. Anti-Z-DNA antibodies were also raised by immunizing animals with poly(dG-dm 5 C).poly(dG-dm 5 C) under conditions where it was reported to be in the left-handed Z conformation as well as unmodified poly(dG-dC).poly(dG-dC) that was in the right-handed B conformation: both were complexed with MBSA. Z-DNA reactive antibodies were found in both murine and human SLE. A Z-DNA-specific as well as a dDNA and Z-DNA cross-reactive antibody population were distinguished by affinity chromatography of the SLE sera. The specificities of the various anti-Z-DNA antibody populations were measured by direct-binding and competitive radioimmunoassays, using synthetic polymers of defined structure under various ionic strengths. These studies allow us to map the possible antigenic sites for these antibodies, which serve as a model for DNA-protein recognition. The findings also established the usefulness of the antibodies as biochemical probes for Z-DNA. 29 references, 6 figures, 1 table
Immunogenicity of ascites tumor cells following in vitro hyperthermia
International Nuclear Information System (INIS)
Dickson, J.A.; Jasiewicz, M.L.; Simpson, A.C.
1982-01-01
The concept that host immunization may be achieved by heat-induced antigenic modifications of cancer cells and/or the release of immunogenic products by dead or dying tumor cells following in vitro heating was examined. Ehrlich ascites cells were used, inasmuch as it was claimed that in vitro hyperthermia increased the immunogenicity of these cells. Tumor cell populations of different viability were obtained by heating Ehrlich cells at 42.5 degrees, 45 degrees, or 60 degrees C. Viable and nonviable cells were separated by Ficoll-Hypaque density centrifugation; viable nonreplicating cells were obtained by treatment with mitomycin C. Cell populations of different viability after heating were left to die slowly over 3 days at 37 degrees C. Swiss TO mice were then given injections of the treated cells and/or medium. No survival benefit occurred in mice inoculated with any of these different components and then challenged with viable tumor cells. Injection of irradiated cells, however, did produce host immunity. Similarly, D23 rat hepatoma ascites cells produced host immunity after 15,000 rad but not after heating. The claim that in vitro hyperthermia increases the immunogenicity of tumor cells was not confirmed
Genome-Derived Cytosolic DNA Mediates Type I Interferon-Dependent Rejection of B Cell Lymphoma Cells
Directory of Open Access Journals (Sweden)
Yu J. Shen
2015-04-01
Full Text Available The DNA damage response (DDR induces the expression of type I interferons (IFNs, but the underlying mechanisms are poorly understood. Here, we show the presence of cytosolic DNA in different mouse and human tumor cells. Treatment of cells with genotoxic agents increased the levels of cytosolic DNA in a DDR-dependent manner. Cloning of cytosolic DNA molecules from mouse lymphoma cells suggests that cytosolic DNA is derived from unique genomic loci and has the potential to form non-B DNA structures, including R-loops. Overexpression of Rnaseh1, which resolves R-loops, reduced the levels of cytosolic DNA, type I Ifn transcripts, and type I IFN-dependent rejection of lymphoma cells. Live-cell imaging showed a dynamic contact of cytosolic DNA with mitochondria, an important organelle for innate immune recognition of cytosolic nucleotides. In summary, we found that cytosolic DNA is present in many tumor cells and contributes to the immunogenicity of tumor cells.
Directory of Open Access Journals (Sweden)
Marina V. Atzingen
2014-01-01
Full Text Available Leptospirosis is an important global disease of human and veterinary concern. Caused by pathogenic Leptospira, the illness was recently classified as an emerging infectious disease. Currently available veterinarian vaccines do not induce long-term protection against infection and do not provide cross-protective immunity. Several studies have suggested the use of DnaK as an antigen in vaccine formulation, due to an exceptional degree of immunogenicity. We focused on four surface proteins: rLIC10368 (Lsa21, rLIC10494, rLIC12690 (Lp95, and rLIC12730, previously shown to be involved in host-pathogen interactions. Our goal was to evaluate the immunogenicity of the proteins genetically fused with DnaK in animal model. The chosen genes were amplified by PCR methodology and cloned into pAE, an E. coli vector. The recombinant proteins were expressed alone or in fusion with DnaK at the N-terminus. Our results demonstrate that leptospiral proteins fused with DnaK have elicited an enhanced immune response in mice when compared to the effect promoted by the individual proteins. The boosted immune effect was demonstrated by the production of total IgG, lymphocyte proliferation, and significant amounts of IL-10 in supernatant of splenocyte cell cultures. We believe that this approach could be employed in vaccines to enhance presentation of antigens of Leptospira to professional immune cells.
Immunogenicity of novel sulfadimethoxide conjugates | Chen ...
African Journals Online (AJOL)
Immunogenicity of novel sulfadimethoxide conjugates. L Chen, J Su, X Zhang, L Li, X He. Abstract. Sulfadimethoxine (SDM) is an antibiotic commonly added to animal feeds. Anti-SDM antibodies are useful for the detection of residual SDM in foods, feeds and biological fluids by ELISA. In this study, we show that SDM is ...
Energy Technology Data Exchange (ETDEWEB)
Davis, P; Russell, A S; Percy, J S
1976-12-01
Antibodies to ultraviolet light denatured DNA (UV DNA) have been measured in patients with systemic lupus erythematosus (SLE) and normal subjects, using a millipore filter radioimmunoassay. High levels of UV DNA binding were only found in patients with SLE. The presence of UV DNA antibodies correlated well with the presence of native DNA antibodies, although immunodiffusion studies and inhibition techniques showed these antibodies to be immunologically distinct in many cases. Forty-one percent of the SLE patients had had photosensitivity at some stage of their disease, but there was a poor correlation between this symptom and the presence of UV DNA antibodies. Although UV DNA is known to be a potent immunogen, none of the results from this study suggests that antibodies to UV DNA are more than another example of the broad spectrum of antinuclear antibodies seen in SLE.
International Nuclear Information System (INIS)
1987-01-01
Immunochemical methods are being developed to quantitate unique DNA base damages in x-irradiated DNA. The approach is to chemically synthesize modified nucleotides, conjugate them to protein carriers, and use the conjugates as immunogens in rabbits. Several thymine ring saturation or fragmentation products have been chosen as models for pyrimidine radiolysis products. These include thymine glycol, dihydrothymine and urea. The characterized antibodies are used to quantitate DNA damage x-irradiated in vitro and to immunochemically characterize the antibody to dihydrothymine. 12 refs., 1 fig., 1 tab
DEFF Research Database (Denmark)
Skov, Kirsten; Bahn, Anne Louise
2017-01-01
Projektets grundlæggende idé er udvikling af visuel, æstetisk læring med Augmented Reality, hvor intentionen er at bidrage med konkrete undersøgelser og udforskning af begrebet Augmented Reality – herunder koblingen mellem det analoge og digitale i forhold til læring, multimodalitet og it...
Strand, Tor Egil Riegels
2008-01-01
This report deals with providing tracking to an outdoor mobile augmented reality system and the Zion Augmented Reality Application. ZionARA is meant to display a virtual recreation of a 13th century castle on the site it once stood through an augmented reality Head Mounted Display. Mobile outdoor augmented/mixed reality puts special demands on what kind of equipment is practical. After briefly evaluating the different existing tracking methods, a solution based on GPS and an augmented inertia...
Ponce, Rafael; Abad, Leslie; Amaravadi, Lakshmi; Gelzleichter, Thomas; Gore, Elizabeth; Green, James; Gupta, Shalini; Herzyk, Danuta; Hurst, Christopher; Ivens, Inge A; Kawabata, Thomas; Maier, Curtis; Mounho, Barbara; Rup, Bonita; Shankar, Gopi; Smith, Holly; Thomas, Peter; Wierda, Dan
2009-07-01
An evaluation of potential antibody formation to biologic therapeutics during the course of nonclinical safety studies and its impact on the toxicity profile is expected under current regulatory guidance and is accepted standard practice. However, approaches for incorporating this information in the interpretation of nonclinical safety studies are not clearly established. Described here are the immunological basis of anti-drug antibody formation to biopharmaceuticals (immunogenicity) in laboratory animals, and approaches for generating and interpreting immunogenicity data from nonclinical safety studies of biotechnology-derived therapeutics to support their progression to clinical evaluation. We subscribe that immunogenicity testing strategies should be adapted to the specific needs of each therapeutic development program, and data generated from such analyses should be integrated with available clinical and anatomic pathology, pharmacokinetic, and pharmacodynamic data to properly interpret nonclinical studies.
Pinto, Ligia A; Dillner, Joakim; Beddows, Simon; Unger, Elizabeth R
2018-01-17
When administered as standard three-dose schedules, the licensed HPV prophylactic vaccines have demonstrated extraordinary immunogenicity and efficacy. We summarize the immunogenicity of these licensed vaccines and the most commonly used serology assays, with a focus on key considerations for one-dose vaccine schedules. Although immune correlates of protection against infection are not entirely clear, both preclinical and clinical evidence point to neutralizing antibodies as the principal mechanism of protection. Thus, immunogenicity assessments in vaccine trials have focused on measurements of antibody responses to the vaccine. Non-inferiority of antibody responses after two doses of HPV vaccines separated by 6 months has been demonstrated and this evidence supported the recent WHO recommendations for two-dose vaccination schedules in both boys and girls 9-14 years of age. There is also some evidence suggesting that one dose of HPV vaccines may provide protection similar to the currently recommended two-dose regimens but robust data on efficacy and immunogenicity of one-dose vaccine schedules are lacking. In addition, immunogenicity has been assessed and reported using different methods, precluding direct comparison of results between different studies and vaccines. New head-to-head vaccine trials evaluating one-dose immunogenicity and efficacy have been initiated and an increase in the number of trials relying on immunobridging is anticipated. Therefore, standardized measurement and reporting of immunogenicity for the up to nine HPV types targeted by the current vaccines is now critical. Building on previous HPV serology assay standardization and harmonization efforts initiated by the WHO HPV LabNet in 2006, new secondary standards, critical reference reagents and testing guidelines will be generated as part of a new partnership to facilitate harmonization of the immunogenicity testing in new HPV vaccine trials. Copyright © 2018 Elsevier Ltd. All rights
Development of a transgenic mouse model to study the immunogenicity of recombinant human insulin
Torosantucci, Riccardo; Brinks, Vera; Kijanka, Grzegorz; Halim, Liem Andhyk; Sauerborn, Melody; Schellekens, Huub; Jiskoot, Wim
2014-01-01
Mouse models are commonly used to assess the immunogenicity of therapeutic proteins and to investigate the immunological processes leading to antidrug antibodies. The aim of this work was to develop a transgenic (TG) Balb/c mouse model for evaluating the immunogenicity of recombinant human insulin
Can dendritic cells improve whole cancer cell vaccines based on immunogenically killed cancer cells?
Cicchelero, Laetitia; Denies, Sofie; Devriendt, Bert; de Rooster, Hilde; Sanders, Niek N
2015-01-01
Immunogenic cell death (ICD) offers interesting opportunities in cancer cell (CC) vaccine manufacture, as it increases the immunogenicity of the dead CC. Furthermore, fusion of CCs with dendritic cells (DCs) is considered a superior method for generating whole CC vaccines. Therefore, in this work, we determined in naive mice whether immunogenically killed CCs per se (CC vaccine) elicit an antitumoral immune response different from the response observed when immunogenically killed CCs are associated with DCs through fusion (fusion vaccine) or through co-incubation (co-incubation vaccine). After tumor inoculation, the type of immune response in the prophylactically vaccinated mice differed between the groups. In more detail, fusion vaccines elicited a humoral anticancer response, whereas the co-incubation and CC vaccine mainly induced a cellular response. Despite these differences, all three approaches offered a prophylactic protection against tumor development in the murine mammary carcinoma model. In summary, it can be concluded that whole CC vaccines based on immunogenically killed CCs may not necessarily require association with DCs to elicit a protective anticancer immune response. If this finding can be endorsed in other cancer models, the manufacture of CC vaccines would greatly benefit from this new insight, as production of DC-based vaccines is laborious, time-consuming and expensive. PMID:26587315
Liao, Hua-Xin; Tomaras, Georgia D.; Bonsignori, Mattia; Tsao, Chun-Yen; Hwang, Kwan-Ki; Chen, Haiyan; Lloyd, Krissey E.; Bowman, Cindy; Sutherland, Laura; Jeffries, Thomas L.; Kozink, Daniel M.; Stewart, Shelley; Anasti, Kara; Jaeger, Frederick H.; Parks, Robert; Yates, Nicole L.; Overman, R. Glenn; Sinangil, Faruk; Berman, Phillip W.; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Karasavva, Nicos; Rerks-Ngarm, Supachai; Kim, Jerome H.; Michael, Nelson L.; Zolla-Pazner, Susan; Santra, Sampa; Letvin, Norman L.; Harrison, Stephen C.
2013-01-01
An immune correlates analysis of the RV144 HIV-1 vaccine trial revealed that antibody responses to the gp120 V1/V2 region correlated inversely with infection risk. The RV144 protein immunogens (A244-rp120 and MN-rgp120) were modified by an N-terminal 11-amino-acid deletion (Δ11) and addition of a herpes simplex virus (HSV) gD protein-derived tag (gD). We investigated the effects of these modifications on gp120 expression, antigenicity, and immunogenicity by comparing unmodified A244 gp120 with both Δ11 deletion and gD tag and with Δ11 only. Analysis of A244 gp120, with or without Δ11 or gD, demonstrated that the Δ11 deletion, without the addition of gD, was sufficient for enhanced antigenicity to gp120 C1 region, conformational V2, and V1/V2 gp120 conformational epitopes. RV144 vaccinee serum IgGs bound more avidly to A244 gp120 Δ11 than to the unmodified gp120, and their binding was blocked by C1, V2, and V1/V2 antibodies. Rhesus macaques immunized with the three different forms of A244 gp120 proteins gave similar levels of gp120 antibody titers, although higher antibody titers developed earlier in A244 Δ11 gp120-immunized animals. Conformational V1/V2 monoclonal antibodies (MAbs) gave significantly higher levels of blocking of plasma IgG from A244 Δ11 gp120-immunized animals than IgG from animals immunized with unmodified A244 gp120, thus indicating a qualitative difference in the V1/V2 antibodies induced by A244 Δ11 gp120. These results demonstrate that deletion of N-terminal residues in the RV144 A244 gp120 immunogen improves both envelope antigenicity and immunogenicity. PMID:23175357
Understanding augmented reality concepts and applications
Craig, Alan B
2013-01-01
Augmented reality is not a technology. Augmented reality is a medium. Likewise, a book on augmented reality that only addresses the technology that is required to support the medium of augmented reality falls far short of providing the background that is needed to produce, or critically consume augmented reality applications. One reads a book. One watches a movie. One experiences augmented reality. Understanding Augmented Reality addresses the elements that are required to create compelling augmented reality experiences. The technology that supports
Generation of Gene-Engineered Chimeric DNA Molecules for Specific Therapy of Autoimmune Diseases
Gesheva, Vera; Szekeres, Zsuzsanna; Mihaylova, Nikolina; Dimitrova, Iliyana; Nikolova, Maria; Erdei, Anna; Prechl, Jozsef
2012-01-01
Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the development of self-reactive B and T cells and autoantibody production. In particular, double-stranded DNA-specific B cells play an important role in lupus progression, and their selective elimination is a reasonable approach for effective therapy of SLE. DNA-based vaccines aim at the induction of immune response against the vector-encoded antigen. Here, we are exploring, as a new DNA-based therapy of SLE, a chimeric DNA molecule encoding a DNA-mimotope peptide, and the Fv but not the immunogenic Fc fragment of an FcγRIIb-specific monoclonal antibody. This DNA construct was inserted in the expression vector pNut and used as a naked DNA vaccine in a mouse model of lupus. The chimeric DNA molecule can be expressed in eukaryotic cells and cross-links cell surface receptors on DNA-specific B cells, delivering an inhibitory intracellular signal. Intramuscular administration of the recombinant DNA molecule to lupus-prone MRL/lpr mice prevented increase in IgG anti-DNA antibodies and was associated with a low degree of proteinuria, modulation of cytokine profile, and suppression of lupus nephritis. PMID:23075110
Immunogenicity and safety of the 9-valent HPV vaccine in men
DEFF Research Database (Denmark)
Castellsagué, X; Giuliano, A R; Goldstone, S
2015-01-01
OBJECTIVES: This study was designed to evaluate the immunogenicity and tolerability of a prophylactic 9-valent HPV (types 6/11/16/18/31/33/45/52/58) VLP (9vHPV) vaccine in young men 16-26 years of age in comparison to young women 16-26 years of age (the population that was used to establish 9v......HPV vaccine efficacy). Safety and immunogenicity data from this study will be used to bridge 9vHPV vaccine efficacy findings in 16-26 year old women to 16-26 year old men. METHODS: This study enrolled 1106 heterosexual men (HM) and 1101 women who had not yet received HPV vaccination. In addition, 313 men...... having sex with men (MSM) were enrolled and were evaluated separately for immunogenicity because previous results showed that antibody responses to quadrivalent HPV (types 6/11/16/18) VLP (qHPV) vaccine were lower in MSM than in HM. All subjects were administered a 3-dose regimen (Day 1, Month 2, Month 6...
International Nuclear Information System (INIS)
Clissa, Patricia Bianca
1997-01-01
Literature data show that 2.0 kGy dose of gamma radiation, generated by 60 source, reduces the toxic activity of Crotalus durissus terrificus venom, without altering its immunogenic capacity. When crotoxin, main toxin from crotalic venom, was irradiated with the same dose, toxicity was also reduced and the immunogenicity was maintained. This fact was attributed to aggregates (compounds with high molecular weight generated during irradiation), that showed no toxicity but were able to induce the antibodies formation against native venom. Crotalus durissus terrificus venom was irradiated with 2.0, 3.0, 5.0 and 10.0 kGy doses and submitted to molecular exclusion chromatography, in order to find an efficient dose that produces large amounts of non toxic but still immunogenic aggregates. After being isolated, the products of irradiation were evaluated for the amount produced, molecular alteration, and toxic and immunogenic activities. These parameters were also analyzed for the whole venom irradiated. The results from different doses irradiated venom were compared with native one, and 2.0 kGy dose was confirmed to be the most efficient in the association of toxicity attenuation with maintenance of immunogenicity of the crotalic venom, while other doses, in spite of being efficient in the toxicity attenuation, they were not able to keep the immunogenicity property. So, the dose of 2.0 kGy could be used to immunize animals in order to improve anticrotalic sera production. (author)
A dermatologist guide to immunogenicity
Directory of Open Access Journals (Sweden)
Collin M. Blattner, DO
2016-09-01
Full Text Available Dermatologists should be aware that autoantibody formation may occur after the initiation of biologic therapy. This phenomenon has been referred to as immunogenicity and biologic fatigue. Because of this, patients may experience loss of clinical efficacy to a particular drug. To combat this phenomenon, low-dose immunomodulators may be used in hopes of preventing autoantibodies. We review the current literature and provide a basic treatment algorithm for patients with moderate to severe psoriasis.
Mucosal immunogenicity of plant lectins in mice
Lavelle, E C; Grant, G; Pusztai, A; Pfüller, U; O’Hagan, D T
2000-01-01
The mucosal immunogenicity of a number of plant lectins with different sugar specificities was investigated in mice. Following intranasal (i.n.) or oral administration, the systemic and mucosal antibody responses elicited were compared with those induced by a potent mucosal immunogen (cholera toxin; CT) and a poorly immunogenic protein (ovalbumin; OVA). After three oral or i.n. doses of CT, high levels of specific serum antibodies were measured and specific IgA was detected in the serum, saliva, vaginal wash, nasal wash and gut wash of mice. Immunization with OVA elicited low titres of serum IgG but specific IgA was not detected in mucosal secretions. Both oral and i.n. delivery of all five plant lectins investigated [Viscum album (mistletoe lectin 1; ML‐1), Lycospersicum esculentum (tomato lectin; LEA), Phaseolus vulgaris (PHA), Triticum vulgaris (wheat germ agglutinin (WGA), Ulex europaeus I (UEA‐1)] stimulated the production of specific serum IgG and IgA antibody after three i.n. or oral doses. Immunization with ML‐1 induced high titres of serum IgG and IgA in addition to specific IgA in mucosal secretions. The response to orally delivered ML‐1 was comparable to that induced by CT, although a 10‐fold higher dose was administered. Immunization with LEA also induced high titres of serum IgG, particularly after i.n. delivery. Low specific IgA titres were also detected to LEA in mucosal secretions. Responses to PHA, WGA and UEA‐1 were measured at a relatively low level in the serum, and little or no specific mucosal IgA was detected. PMID:10651938
Henmar, H; Lund, G; Lund, L; Petersen, A; Würtzen, P A
2008-09-01
Different vaccines containing intact allergens or chemically modified allergoids as active ingredients are commercially available for specific immunotherapy. Allergoids are claimed to have decreased allergenicity without loss of immunogenicity and this is stated to allow administration of high allergoid doses. We compared the allergenicity and immunogenicity of four commercially available chemically modified grass pollen allergoid products with three commercially available intact grass pollen allergen vaccines. The allergenicity was investigated with immunoglobulin (Ig)E-inhibition and basophil activation assays. Human T cell proliferation and specific IgG-titres following mouse immunizations were used to address immunogenicity. Furthermore, intact allergen vaccines with different contents of active ingredients were selected to study the influence of the allergen dose. In general, a lower allergenicity for allergen vaccines was clearly linked to a reduced immunogenicity. Compared with the vaccine with the highest amount of intact allergen, the allergoids caused reduced basophil activation as well as diminished immunogenicity demonstrated by reduced T cell activation and/or reduced induction of murine grass-specific IgG antibodies. Interestingly, intact allergen vaccines with lower content of active ingredient exhibited similarly reduced allergenicity, while immunogenicity was still higher or equal to that of allergoids. The low allergenicity observed for some allergoids was inherently linked to a significantly lower immunogenic response questioning the rationale behind the chemical modification into allergoids. In addition, the linkage between allergenicity, immunogenicity and dose found for intact allergen vaccines and the immunogen as well as allergenic immune responses observed for allergoids suggest that the modified allergen vaccines do not contain high doses of immunologically active ingredients.
Directory of Open Access Journals (Sweden)
Xiankai Liu
Full Text Available Immunoproteomics was used to screen the immunogenic spore and vegetative proteins of Bacillus anthracis vaccine strain A16R. The spore and vegetative proteins were separated by 2D gel electrophoresis and transferred to polyvinylidene difluoride membranes, and then western blotting was performed with rabbit immune serum against B.anthracis live spores. Immunogenic spots were cut and digested by trypsin. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry was performed to identify the proteins. As a result, 11 and 45 immunogenic proteins were identified in the spores and vegetative cells, respectively; 26 of which have not been reported previously. To verify their immunogenicity, 12 of the identified proteins were selected to be expressed, and the immune sera from the mice vaccinated by the 12 expressed proteins, except BA0887, had a specific western blot band with the A16R whole cellular lytic proteins. Some of these immunogenic proteins might be used as novel vaccine candidates themselves or for enhancing the protective efficacy of a protective-antigen-based vaccine.
Antigen-antibody reactions of UV-irradiated phage DNA
International Nuclear Information System (INIS)
Fink, A.
1976-01-01
The observation of others could be confirmed that UV-irradiated DNA is a better immunogen than unirradiated DNA. The author's immune sera contained a high amount of antibodies with a specific action against photoproducts in the DNA. The thymine dimer was identified as relevant photoproduct and thus as antigenic determinant. In comparison, the amount of unspecific antibodies reacting with denaturated DNA was low and varied between sera. Thymin-dimer antibodies showed a high specificity without cross-reaction with other pyrimidine dimers such as anti CC and anti CT; they belong to the class of IgG molecules. UV-irradiated dinucleotide dTpT is sufficient to induce the formation of antibodies reacting with the cis-syn thymine dimers in UV-irradiated DNA. Antibody binding is proportional to the UV doses applied to the DNA. When using completely denaturated DNA, there is a linear increase changing into a plateau at higher doses. The extent of antigen-antibody binding is strongly dependent on the degree of denaturation of the DNA. With increasing denaturation, the antibody binding of the DNA increases. The antigen-antibody reaction can thus be used to estimate the degree of denaturation of the DNA. There were no signs of an influence of the degree of denaturation of the DNA on the quantum yield of thymine dimers. The different amounts of antibodies is therefore due to the masking of thymine dimers in native DNA. When irradiating intact phage particles, there was no sign of an influence of the phages' protein covers on the antibody binding capacity of DNA compared with DNA irradiated in vitro. (orig.) [de
A Multiantigenic DNA Vaccine That Induces Broad Hepatitis C Virus-Specific T-Cell Responses in Mice.
Gummow, Jason; Li, Yanrui; Yu, Wenbo; Garrod, Tamsin; Wijesundara, Danushka; Brennan, Amelia J; Mullick, Ranajoy; Voskoboinik, Ilia; Grubor-Bauk, Branka; Gowans, Eric J
2015-08-01
There are 3 to 4 million new hepatitis C virus (HCV) infections annually around the world, but no vaccine is available. Robust T-cell mediated responses are necessary for effective clearance of the virus, and DNA vaccines result in a cell-mediated bias. Adjuvants are often required for effective vaccination, but during natural lytic viral infections damage-associated molecular patterns (DAMPs) are released, which act as natural adjuvants. Hence, a vaccine that induces cell necrosis and releases DAMPs will result in cell-mediated immunity (CMI), similar to that resulting from natural lytic viral infection. We have generated a DNA vaccine with the ability to elicit strong CMI against the HCV nonstructural (NS) proteins (3, 4A, 4B, and 5B) by encoding a cytolytic protein, perforin (PRF), and the antigens on a single plasmid. We examined the efficacy of the vaccines in C57BL/6 mice, as determined by gamma interferon enzyme-linked immunosorbent spot assay, cell proliferation studies, and intracellular cytokine production. Initially, we showed that encoding the NS4A protein in a vaccine which encoded only NS3 reduced the immunogenicity of NS3, whereas including PRF increased NS3 immunogenicity. In contrast, the inclusion of NS4A increased the immunogenicity of the NS3, NS4B, andNS5B proteins, when encoded in a DNA vaccine that also encoded PRF. Finally, vaccines that also encoded PRF elicited similar levels of CMI against each protein after vaccination with DNA encoding NS3, NS4A, NS4B, and NS5B compared to mice vaccinated with DNA encoding only NS3 or NS4B/5B. Thus, we have developed a promising "multiantigen" vaccine that elicits robust CMI. Since their development, vaccines have reduced the global burden of disease. One strategy for vaccine development is to use commercially viable DNA technology, which has the potential to generate robust immune responses. Hepatitis C virus causes chronic liver infection and is a leading cause of liver cancer. To date, no vaccine is
Directory of Open Access Journals (Sweden)
Sander Bekeschus
2017-01-01
Full Text Available Metastatic melanoma is an aggressive and deadly disease. Therapeutic advance has been achieved by antitumor chemo- and radiotherapy. These modalities involve the generation of reactive oxygen and nitrogen species, affecting cellular viability, migration, and immunogenicity. Such species are also created by cold physical plasma, an ionized gas capable of redox modulating cells and tissues without thermal damage. Cold plasma has been suggested for anticancer therapy. Here, melanoma cell toxicity, motility, and immunogenicity of murine metastatic melanoma cells were investigated following plasma exposure in vitro. Cells were oxidized by plasma, leading to decreased metabolic activity and cell death. Moreover, plasma decelerated melanoma cell growth, viability, and cell cycling. This was accompanied by increased cellular stiffness and upregulation of zonula occludens 1 protein in the cell membrane. Importantly, expression levels of immunogenic cell surface molecules such as major histocompatibility complex I, calreticulin, and melanocortin receptor 1 were significantly increased in response to plasma. Finally, plasma treatment significantly decreased the release of vascular endothelial growth factor, a molecule with importance in angiogenesis. Altogether, these results suggest beneficial toxicity of cold plasma in murine melanomas with a concomitant immunogenicity of potential interest in oncology.
Son, Keum-Joo; Choi, Ki Ryung; Lee, Seog Jae; Lee, Hyunah
2016-02-01
Cancer is one of the leading causes of morbidity and mortality worldwide; therefore there is a need to discover new therapeutic modules with improved efficacy and safety. Immune-(cell) therapy is a promising therapeutic strategy for the treatment of intractable cancers. The effectiveness of certain chemotherapeutics in inducing immunogenic tumor cell death thus promoting cancer eradication has been reported. Ginsenoside Rg3 is a ginseng saponin that has antitumor and immunomodulatory activity. In this study, we treated tumor cells with Rg3 to verify the significance of inducing immunogenic tumor cell death in antitumor therapy, especially in DC-based immunotherapy. Rg3 killed the both immunogenic (B16F10 melanoma cells) and non-immunogenic (LLC: Lewis Lung Carcinoma cells) tumor cells by inducing apoptosis. Surface expression of immunogenic death markers including calreticulin and heat shock proteins and the transcription of relevant genes were increased in the Rg3-dying tumor. Increased calreticulin expression was directly related to the uptake of dying tumor cells by dendritic cells (DCs): the proportion of CRT(+) CD11c(+) cells was increased in the Rg3-treated group. Interestingly, tumor cells dying by immunogenic cell death secreted IFN-γ, an effector molecule for antitumor activity in T cells. Along with the Rg3-induced suppression of pro-angiogenic (TNF-α) and immunosuppressive cytokine (TGF-β) secretion, IFN-γ production from the Rg3-treated tumor cells may also indicate Rg3 as an effective anticancer immunotherapeutic strategy. The data clearly suggests that Rg3-induced immunogenic tumor cell death due its cytotoxic effect and its ability to induce DC function. This indicates that Rg3 may be an effective immunotherapeutic strategy.
Identification of immunogenic and virulence-associated Campylobacter jejuni proteins
DEFF Research Database (Denmark)
Nielsen, Lene Nørby; Luijkx, Thomas A.; Vegge, Christina Skovgaard
2012-01-01
With the aim of identifying proteins important for host interaction and virulence, we have screened an expression library of NCTC 11168 Campylobacter jejuni genes for highly immunogenic proteins. A commercial C. jejuni open reading frame (ORF) library consisting of more than 1,600 genes was trans......With the aim of identifying proteins important for host interaction and virulence, we have screened an expression library of NCTC 11168 Campylobacter jejuni genes for highly immunogenic proteins. A commercial C. jejuni open reading frame (ORF) library consisting of more than 1,600 genes...
Peng, Xi; Tang, Zhiqiang; Yang, Fei; Feris, Rogerio; Metaxas, Dimitris
2018-01-01
Random data augmentation is a critical technique to avoid overfitting in training deep neural network models. However, data augmentation and network training are usually treated as two isolated processes, limiting the effectiveness of network training. Why not jointly optimize the two? We propose adversarial data augmentation to address this limitation. The main idea is to design an augmentation network (generator) that competes against a target network (discriminator) by generating `hard' au...
Confronting an augmented reality
Directory of Open Access Journals (Sweden)
John Hedberg
2012-08-01
Full Text Available How can educators make use of augmented reality technologies and practices to enhance learning and why would we want to embrace such technologies anyway? How can an augmented reality help a learner confront, interpret and ultimately comprehend reality itself? In this article, we seek to initiate a discussion that focuses on these questions, and suggest that they be used as drivers for research into effective educational applications of augmented reality. We discuss how multi-modal, sensorial augmentation of reality links to existing theories of education and learning, focusing on ideas of cognitive dissonance and the confrontation of new realities implied by exposure to new and varied perspectives. We also discuss connections with broader debates brought on by the social and cultural changes wrought by the increased digitalisation of our lives, especially the concept of the extended mind. Rather than offer a prescription for augmentation, our intention is to throw open debate and to provoke deep thinking about what interacting with and creating an augmented reality might mean for both teacher and learner.
DNA in the conservation and management of African antelope
DEFF Research Database (Denmark)
Lorenzen, Eline
2016-01-01
tool in informed species conservation and sustainable wildlife management. The movement of antelope through translocations, reintroductions, and population augmentations is common practice in wildlife management. DNA-led species identification using genetic barcoding is an effective use of genetic data...... within forensics. DNA barcoding is a taxonomic method that uses a short genetic marker in an organism's DNA to identify it as belonging to a particular species....... databases, and represents a valuable reference database of antelope DNA diversity. For the evolution of antelope, sub-Saharan Africa is a region of particular intrigue. The geographic regions of sub-Saharan Africa represent unique evolutionary scenarios. Molecular data have become an increasingly important...
Directory of Open Access Journals (Sweden)
Wei Li
2013-12-01
Full Text Available Recent studies indicate that DNA immunization is powerful in eliciting antigen-specific antibody responses in both animal and human studies. However, there is limited information on the mechanism of this effect. In particular, it is not known whether DNA immunization can also enhance the development of antigen-specific B cell development. In this report, a pilot study was conducted using plague LcrV immunogen as a model system to determine whether DNA immunization is able to enhance LcrV-specific B cell development in mice. Plague is an acute and often fatal infectious disease caused by Yersinia pestis (Y. pestis. Humoral immune responses provide critical protective immunity against plague. Previously, we demonstrated that a DNA vaccine expressing LcrV antigen can protect mice from lethal mucosal challenge. In the current study, we further evaluated whether the use of a DNA priming immunization is able to enhance the immunogenicity of a recombinant LcrV protein vaccine, and in particular, the development of LcrV-specific B cells. Our data indicate that DNA immunization was able to elicit high-level LcrV antibody responses when used alone or as part of a prime-boost immunization approach. Most significantly, DNA immunization was also able to increase the levels of LcrV-specific B cell development. The finding that DNA immunization can enhance antigen-specific B cell responses is highly significant and will help guide similar studies in other model antigen systems.
Yang, Hung-Wei; Ye, Ling; Guo, Xin Dong; Yang, Chinglai; Compans, Richard W; Prausnitz, Mark R
2017-01-01
Ebola DNA vaccine is incorporated into PLGA-PLL/γPGA nanoparticles and administered to skin using a microneedle (MN) patch. The nanoparticle delivery system increases vaccine thermostability and immunogenicity compared to free vaccine. Vaccination by MN patch produces stronger immune responses than intramuscular administration. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
2017-10-01
ELISA or... ELISA or quantitative immunofluorescence microscopy Ø Planned activity duration in SOW: 2017 Q1 – 2017 Q3 Ø Proportion of subtask completed: 0% Ø...Subtask 3A: i) validate mouse cell findings using chemiluminescent electrophoretic mobility shift assays (or DNA-binding ELISA technique in
Directory of Open Access Journals (Sweden)
T. V. Korotaeva
2015-01-01
Full Text Available The present-day views of the immunogenicity of biological agents (BAs used to in the treatment of psoriasis and psoriatic arthritis are analyzed. The immunogenicity of these medicaments is noted to depend on their molecular structure, individual patient characteristics, and used treatment regimens. As this takes place, the primary structure of the drug and its posttranslation modifications during manufacture are key factors. It is pointed out that a number of antigenic structures may give rise to the body's BA antibodies – murine epitopes, idiotopes, and allotropes, neoantigens forming in the coupling area of hybrid proteins, nonlinear epitopes present in the aggregated preparations. BAs that tend to form large immune complexes with these antibodies are most immunogenic. The antibodies to most BAs, except drugs based on soluble tumor necrosis factor-α receptors (etanercept, are neutralizing, i.e. they affect the efficiency of therapy, particularly when used over a long period of time.The results of trials evaluating the impact of antibodies to BAs on their clinical value are considered. It is believed that immunogenicity is itself of great importance in respect to the occurrence of the escape phenomenon of a response to BA therapy and to its safety. Attention is drawn to immunogenicity diagnostic problems; at the same it is noted that none of the used laboratory diagnostic techniques can reveal individual BA antibody forms and isotypes. It is concluded that there is a need for further investigations to standardize optimal methods for diagnosing neutralizing antibodies, to elaborate criteria for predicting a response to therapy in terms of an immunogenicity factor, and to reveal pathogenetic mechanisms responsible for the production of antibodies to BAs. The design of novel medicaments with minimal immunogenicity will depend on whether these mechanisms are common to all drugs or specific.
Increased humoral immunity by DNA vaccination using an alpha-tocopherol-based adjuvant
DEFF Research Database (Denmark)
Karlsson, Ingrid; Borggren, Marie; Nielsen, Jens
2017-01-01
approaches. We tested whether the emulsion-based and alpha-tocopherol containing adjuvant Diluvac Forte® has the ability to enhance the immunogenicity of a naked DNA vaccine (i.e., plasmid DNA). As a model vaccine, we used plasmids encoding both a surface-exposed viral glycoprotein (hemagglutinin......) and an internal non-glycosylated nucleoprotein in the Th1/Th2 balanced CB6F1 mouse model. The naked DNA (50 µg) was premixed at a 1:1 volume/volume ratio with Diluvac Forte®, an emulsion containing different concentrations of alpha-tocopherol, the emulsion alone or endotoxin-free phosphate-buffered saline (PBS......). The animals received two intracutaneous immunizations spaced 3 weeks apart. When combined with Diluvac Forte® or the emulsion containing alpha-tocopherol, the DNA vaccine induced a more potent and balanced immunoglobulin G (IgG)1 and IgG2c response, and both IgG subclass responses were significantly enhanced...
Duong, Huu Thuy Trang; Kim, Nak Won; Thambi, Thavasyappan; Giang Phan, V H; Lee, Min Sang; Yin, Yue; Jeong, Ji Hoon; Lee, Doo Sung
2018-01-10
Successful delivery of a DNA vaccine to antigen-presenting cells and their subsequent stimulation of CD4 + and CD8 + T cell immunity remains an inefficient process. In general, the delivery of prophylactic vaccines is mainly mired by low transfection efficacy, poor immunogenicity, and safety issues from the materials employed. Currently, several strategies have been exploited to improve immunogenicity, but an effective strategy for safe and pain-free delivery of DNA vaccines is complicated. Herein, we report the rapid delivery of polyplex-based DNA vaccines using microneedle arrays coated with a polyelectrolyte multilayer assembly of charge reversal pH-responsive copolymer and heparin. The charge reversal pH-responsive copolymer, composed of oligo(sulfamethazine)-b-poly(ethylene glycol)-b-poly(amino urethane) (OSM-b-PEG-b-PAEU), was used as a triggering layer in the polyelectrolyte multilayer assembly on microneedles. Charge reversal characteristics of this copolymer, that is, the OSM-b-PEG-b-PAEU copolymer exhibit, positive charge at low pH (pH4.03) and becoming negative charge when exposed to physiological pH conditions (pH7.4), allowing the facile assembly and disassembly of polyelectrolyte multilayers. The electrostatic repulsion between heparin and OSM-b-PEG-b-PAEU charge reversal copolymer triggered the release of DNA vaccines. DNA vaccines laden on microneedles are effectively transfected into RAW 264.7 macrophage cells in vitro. Vaccination of BALB/c mice by DNA vaccine-loaded microneedle arrays coated with a polyelectrolyte multilayer generated antigen-specific robust immune responses. These findings provide potential strategy of charge reversal pH-responsive copolymers coated microneedles for DNA vaccine delivery. Copyright © 2017. Published by Elsevier B.V.
Development of cancer immunotherapy
International Nuclear Information System (INIS)
Yun, Yeon Sook; Chung, H. Y.; Yi, S. Y.; Kim, K. W.; Kim, B. K.; Chung, I. S.; Park, J. Y.
1999-04-01
To increase the curative rate of cancer patients, we developed ideal biological response modifier from medicinal plants: Ginsan, KC68IId-8, KC-8Ala, KG-30. Ginsan activated natural killer cell activity of spleen cells more than 5.4 times than lentinan, 1.4 times than picibanil. Radioprotective activity of Ginsan is stronger than WR2721, glucan, and selenium. The immunogenicity of MOPC tumor cells was augmented by treatment with IL-10 antisense oligonucleotide and by transfection with VEGF sense-, antisense gene. The immunogenicity of MOPC tumor cells was augmented by treatment with IL-10 antisense oligonucleotide and by transfection with VEGF sense-, antisense gene. The immunogenicity of A20 tumor cells was also augmented by transfection with B7.1 gene. The immunosuppression of gamma-irradiation was due to the reduction of Th1 sytokine gene expression through STAT pathway. These research will devote to develop new cancer immunotherapy and to reduce side effect of cancer radiotherapy and chemotherapy
Development of cancer immunotherapy
Energy Technology Data Exchange (ETDEWEB)
Yun, Yeon Sook; Chung, H. Y.; Yi, S. Y.; Kim, K. W.; Kim, B. K.; Chung, I. S.; Park, J. Y
1999-04-01
To increase the curative rate of cancer patients, we developed ideal biological response modifier from medicinal plants: Ginsan, KC68IId-8, KC-8Ala, KG-30. Ginsan activated natural killer cell activity of spleen cells more than 5.4 times than lentinan, 1.4 times than picibanil. Radioprotective activity of Ginsan is stronger than WR2721, glucan, and selenium. The immunogenicity of MOPC tumor cells was augmented by treatment with IL-10 antisense oligonucleotide and by transfection with VEGF sense-, antisense gene. The immunogenicity of MOPC tumor cells was augmented by treatment with IL-10 antisense oligonucleotide and by transfection with VEGF sense-, antisense gene. The immunogenicity of A20 tumor cells was also augmented by transfection with B7.1 gene. The immunosuppression of gamma-irradiation was due to the reduction of Th1 sytokine gene expression through STAT pathway. These research will devote to develop new cancer immunotherapy and to reduce side effect of cancer radiotherapy and chemotherapy.
Rajadhyaksha, Manoj; Subramanyam, Meena; Rup, Bonnie
2013-10-01
The immunogenicity profile of a biotherapeutic is determined by multiple product-, process- or manufacturing-, patient- and treatment-related factors and the bioanalytical methodology used to monitor for immunogenicity. This creates a complex situation that limits direct correlation of individual factors to observed immunogenicity rates. Therefore, mechanistic understanding of how these factors individually or in concert could influence the overall incidence and clinical risk of immunogenicity is crucial to provide the best benefit/risk profile for a given biotherapeutic in a given indication and to inform risk mitigation strategies. Advances in the field of immunogenicity have included development of best practices for monitoring anti-drug antibody development, categorization of risk factors contributing to immunogenicity, development of predictive tools, and development of effective strategies for risk management and mitigation. Thus, the opportunity to ask "where we are now and where we would like to go from here?" was the main driver for organizing an Open Forum on Improving Immunogenicity Risk Prediction and Management, conducted at the 2012 American Association of Pharmaceutical Scientists' (AAPS) National Biotechnology Conference in San Diego. The main objectives of the Forum include the following: to understand the nature of immunogenicity risk factors, to identify analytical tools used and animal models and management strategies needed to improve their predictive value, and finally to identify collaboration opportunities to improve the reliability of risk prediction, mitigation, and management. This meeting report provides the Forum participant's and author's perspectives on the barriers to advancing this field and recommendations for overcoming these barriers through collaborative efforts.
Inhibiting the repair of DNA damage induced by gamma irradiation in rat thymocytes
International Nuclear Information System (INIS)
Smit, J.A.; Stark, J.H.
1994-01-01
This study assessed the ability of 11 established and potential radiosensitizing agents to retard the repair of radiation-induced DNA damage with a view to enhancing the immunosuppressive effects of in vivo lymphoid irradiation. The capability of irradiated rat thymocytes to repair DNA damage was assessed by an adaptation of the fluorimetric unwinding method. Three compounds, 3-aminobenzamide (3-AB), novobiocin and flavone-8-acetic acid (FAA), inhibited repair significantly. We also report the effect of low-dose irradiation combined with repair inhibitors on the relationship between DNA strand breaks, fragmentation, cell viability and use of nicotinamide adenine dinucleotide (NAD). DNA fragmentation was increased by 1 mM/l FAA, 1 mM/l novobiocin and 50 μM/l RS-61443 within 3 h of incubation. The latter two compounds also proved cytotoxic. All three drugs augmented the effect of ionizing radiation on the use of NAD. Of the agents investigated, FAA showed the most promise for augmenting the immunosuppressive action of irradiation at nontoxic, pharmacokinetically achievable concentrations. 33 refs., 1 fig., 2 tabs
Immunogenicity and safety of an acellular pertussis, diphtheria ...
African Journals Online (AJOL)
Objective. To assess the immunogenicity and safety data for a pentavalent combination vaccine containing acellular pertussis, inactivated poliovirus, and Haemophilus influenzae (Hib) polysaccharide-conjugate antigens. Methods. A DTaP-IPV//PRP~T vaccine (Pentaxim™) was given at 6, 10 and 14 weeks of age to 212 ...
Immunogenic Apoptosis as a Novel Tool for Anticancer Vaccine Development
Directory of Open Access Journals (Sweden)
Barbara Montico
2018-02-01
Full Text Available Immunogenic apoptosis, or more appropriately called immunogenic cell death (ICD, is a recently described form of apoptosis induced by a specific set of chemotherapeutic drugs or by physical therapeutic modalities, such as ionizing irradiation and photodynamic therapy. The peculiar characteristic of ICD is the ability to favor recognition and elimination of dying tumor cells by phagocytes in association with the release of pro-inflammatory molecules (such as cytokines and high-mobility group box-1. While in vitro and animal models pointed to ICD as one of the molecular mechanisms mediating the clinical efficacy of some anticancer agents, it is hard to clearly demonstrate its contribution in cancer patients. Clinical evidence suggests that the induction of ICD alone is possibly not sufficient to fully subvert the immunosuppressive tumor microenvironment. However, interesting results from recent studies contemplate the exploitation of ICD for improving the immunogenicity of cancer cells to use them as an antigen cargo in the development of dendritic cell (DC vaccines. Herein, we discuss the effects of danger signals expressed or released by cancer cells undergoing ICD on the maturation and activation of immature and mature DC, highlighting the potential added value of ICD in adoptive immunotherapy protocols.
Mobile Augmented Reality Applications
Prochazka, David; Stencl, Michael; Popelka, Ondrej; Stastny, Jiri
2011-01-01
Augmented reality have undergone considerable improvement in past years. Many special techniques and hardware devices were developed, but the crucial breakthrough came with the spread of intelligent mobile phones. This enabled mass spread of augmented reality applications. However mobile devices have limited hardware capabilities, which narrows down the methods usable for scene analysis. In this article we propose an augmented reality application which is using cloud computing to enable using...
Greub, Gilbert; Kebbi-Beghdadi, Carole; Bertelli, Claire; Collyn, François; Riederer, Beat M; Yersin, Camille; Croxatto, Antony; Raoult, Didier
2009-12-23
With the availability of new generation sequencing technologies, bacterial genome projects have undergone a major boost. Still, chromosome completion needs a costly and time-consuming gap closure, especially when containing highly repetitive elements. However, incomplete genome data may be sufficiently informative to derive the pursued information. For emerging pathogens, i.e. newly identified pathogens, lack of release of genome data during gap closure stage is clearly medically counterproductive. We thus investigated the feasibility of a dirty genome approach, i.e. the release of unfinished genome sequences to develop serological diagnostic tools. We showed that almost the whole genome sequence of the emerging pathogen Parachlamydia acanthamoebae was retrieved even with relatively short reads from Genome Sequencer 20 and Solexa. The bacterial proteome was analyzed to select immunogenic proteins, which were then expressed and used to elaborate the first steps of an ELISA. This work constitutes the proof of principle for a dirty genome approach, i.e. the use of unfinished genome sequences of pathogenic bacteria, coupled with proteomics to rapidly identify new immunogenic proteins useful to develop in the future specific diagnostic tests such as ELISA, immunohistochemistry and direct antigen detection. Although applied here to an emerging pathogen, this combined dirty genome sequencing/proteomic approach may be used for any pathogen for which better diagnostics are needed. These genome sequences may also be very useful to develop DNA based diagnostic tests. All these diagnostic tools will allow further evaluations of the pathogenic potential of this obligate intracellular bacterium.
DEFF Research Database (Denmark)
Wang, Mingjun; Bai, Fang; Pries, Mette
2006-01-01
PURPOSE: To identify H-2 Kb/Db-binding immunogenic peptides derived from retinal proteins. METHODS: Computer-based prediction was used to identify potentially H-2 Kb/Db-binding peptides derived from the interphotoreceptor retinol-binding protein (IRBP), soluble retinal antigen (S...... on day 21 after immunization with IRBP or IRBP and the immunogenic peptides. RESULTS: All the 21 predicted peptides were found to upregulate expression of H-2 Kb/Db on RMA-S cells. Five peptides, the two IRBP-derived peptides IRBP89-96 and IRBP(101-108), and the three PEDF-derived peptides, PEDF389....... The immunogenic peptides alone did not induce inflammation in the eyes, but they could enhance severity of uveitis induced by IRBP. CONCLUSIONS: Five of 21 H-2 Kb/Db-binding retinal protein-derived peptides were found to be immunogenic, suggesting that these peptides could function as autoantigenic epitopes...
Augmenting Clozapine With Sertindole
DEFF Research Database (Denmark)
Nielsen, Jimmi; Emborg, Charlotte; Gydesen, Susanne
2012-01-01
Clozapine augmentation with antipsychotic drugs is widely used despite sparse evidence supporting this strategy. Sertindole is a nonsedating atypical antipsychotic drug with low affinity for cholinergic receptors, which makes it potentially suitable for augmentation of clozapine. The study design...... glucose, lipids, and electrocardiogram. Clozapine augmentation with sertindole was not superior to placebo regarding total score or subscale score of the Positive and Negative Syndrome Scale, Clinical Global Impression, World Health Organization Quality of Life Brief, or Drug Attitude Inventory....... No increased adverse effects compared with placebo were found. Four patients randomized to sertindole experienced a significant worsening of psychosis, and 2 of them required psychiatric admission. Metabolic parameters were unchanged during the study, but augmentation of clozapine with sertindole...
[Augmentation technique on the proximal humerus].
Scola, A; Gebhard, F; Röderer, G
2015-09-01
The treatment of osteoporotic fractures is still a challenge. The advantages of augmentation with respect to primary in vitro stability and the clinical use for the proximal humerus are presented in this article. In this study six paired human humeri were randomized into an augmented and a non-augmented group. Osteosynthesis was performed with a PHILOS plate (Synthes®). In the augmented group the two screws finding purchase in the weakest cancellous bone were augmented. The specimens were tested in a 3-part fracture model in a varus bending test. The augmented PHILOS plates withstood significantly more load cycles until failure. The correlation to bone mineral density (BMD) showed that augmentation could partially compensate for low BMD. The augmentation of the screws in locked plating in a proximal humerus fracture model is effective in improving the primary stability in a cyclic varus bending test. The targeted augmentation of two particular screws in a region of low bone quality within the humeral head was almost as effective as four screws with twice the amount of bone cement. Screw augmentation combined with a knowledge of the local bone quality could be more effective in enhancing the primary stability of a proximal humerus locking plate because the effect of augmentation can be exploited more effectively limiting it to the degree required. The technique of augmentation is simple and can be applied in open and minimally invasive procedures. When the correct procedure is used, complications (cement leakage into the joint) can be avoided.
Augmented reality and ubiquitous computing : The hidden potentialities of augmented reality
Liberati, Nicola
2016-01-01
The aim of this paper was to highlight the augmented reality’s potentialities, depicting its main characteristics and focusing attention on what its goal should be in order to have a new technology completely different from those that already exist. From a technological point of view, augmented
Myzithras, Maria; Bigwarfe, Tammy; Li, Hua; Waltz, Erica; Ahlberg, Jennifer; Giragossian, Craig; Roberts, Simon
Prior to clinical studies, the pharmacokinetics (PK) of antibody-based therapeutics are characterized in preclinical species; however, those species can elicit immunogenic responses that can lead to an inaccurate estimation of PK parameters. Immunodeficient (SCID) transgenic hFcRn and C57BL/6 mice were used to characterize the PK of three antibodies that were previously shown to be immunogenic in mice and cynomolgus monkeys. Four mouse strains, Tg32 hFcRn SCID, Tg32 hFcRn, SCID and C57BL/6, were administered adalimumab (Humira®), mAbX and mAbX-YTE at 1 mg/kg, and in SCID strains there was no incidence of immunogenicity. In non-SCID strains, drug-clearing ADAs appeared after 4-7 days, which affected the ability to accurately calculate PK parameters. Single species allometric scaling of PK data for Humira® in SCID and hFcRn SCID mice resulted in improved human PK predictions compared to C57BL/6 mice. Thus, the SCID mouse model was demonstrated to be a useful tool for assessing the preclinical PK of immunogenic therapeutics.
Capillary Refill using Augmented Reality
Clausen, Christoffer
2017-01-01
Master's thesis in Computer science The opportunities within augmented reality is growing. Augmented reality is a combination of the real and the virtual world in real time, and large companies like Microsoft and Google is now investing heavily in the technology. This thesis presents a solution for simulating a medical test called capillary refill, by using augmented reality. The simulation is performed with an augmented reality headset called HoloLens. The HoloLens will recognise a mark...
The safety and immunogenicity of influenza vaccine in children with asthma in Mexico.
Pedroza, Alvaro; Huerta, José G; Garcia, Maria de la Luz; Rojas, Arsheli; López-Martínez, Irma; Penagos, Martín; Franco-Paredes, Carlos; Deroche, Christele; Mascareñas, Cesar
2009-07-01
The morbidity and mortality associated with influenza is substantial in children with asthma. There are no available data on the safety and immunogenicity of influenza vaccine in children with asthma in Latin America. Furthermore, it is unclear if influenza vaccination may cause asthma exacerbations. We conducted a placebo-controlled trial to investigate the safety and immunogenicity of an inactivated trivalent split virus influenza vaccine in children with asthma in Mexico. We also measured the impact of influenza vaccination on pulmonary function tests in this population. The inactivated influenza vaccine was immunogenic and safe in terms of local and systemic side effects compared to placebo. We observed no significant impact on pulmonary function tests among vaccine recipients. Given the significant morbidity associated with influenza in children, strategies to promote increased influenza vaccination coverage in this high-risk group in Latin America and elsewhere are urgently needed.
Augmented Mirror: Interactive Augmented Reality System Based on Kinect
Vera , Lucía; Gimeno , Jesús; Coma , Inmaculada; Fernández , Marcos
2011-01-01
Part 1: Long and Short Papers; International audience; In this paper we present a virtual character controlled by an actor in real time, who talks with an audience through an augmented mirror. The application, which integrates video images, the avatar and other virtual objects within an Augmented Reality system, has been implemented using a mixture of technologies: two kinect systems for motion capture, depth map and real images, a gyroscope to detect head movements, and control algorithms to...
Augmented reality in neurosurgery.
Tagaytayan, Raniel; Kelemen, Arpad; Sik-Lanyi, Cecilia
2018-04-01
Neurosurgery is a medical specialty that relies heavily on imaging. The use of computed tomography and magnetic resonance images during preoperative planning and intraoperative surgical navigation is vital to the success of the surgery and positive patient outcome. Augmented reality application in neurosurgery has the potential to revolutionize and change the way neurosurgeons plan and perform surgical procedures in the future. Augmented reality technology is currently commercially available for neurosurgery for simulation and training. However, the use of augmented reality in the clinical setting is still in its infancy. Researchers are now testing augmented reality system prototypes to determine and address the barriers and limitations of the technology before it can be widely accepted and used in the clinical setting.
CYD-TDV dengue vaccine: systematic review and meta-analysis of efficacy, immunogenicity and safety.
Godói, Isabella Piassi; Lemos, Livia Lovato Pires; de Araújo, Vânia Eloisa; Bonoto, Braúlio Cesar; Godman, Brian; Guerra Júnior, Augusto Afonso
2017-03-01
Dengue virus (DENV) is a serious global health problem. CYD-TDC (Dengvaxia ® ) was the first vaccine to gain regulatory approval to try and address this problem. Summarize all available evidence on the immunogenicity, efficacy and safety of the CYD-TDV dengue vaccine. Meta-analysis and systematic review. The best and worst immunogenicity results were for DENV4 and DENV1, respectively. Vaccine efficacy of 60% was derived from studies with participants aged 2-16 years old, with DENV4 and DENV2 presenting the best and worst results, respectively. Erythema and swelling were more frequent with CYD-TDV. No differences were detected for systemic adverse events. CYD-TDV showed moderate efficacy in children and adolescents. From the immunogenicity results in adults, we can expect satisfactory efficacy from vaccination in this population.
FDA advisory committees meet January 26 on Salk HIV-1 immunogen.
1995-01-06
Two advisory committees of the Food and Drug Administration (FDA) will meet to consider future trials of the HIV-1 immunogen developed by Dr. Jonas Salk. The Immune Response Corporation has already conducted several studies of the immunogen, and has found improvement in various immunological and other blood tests, and no adverse effects. However, the studies have not been large enough to show conclusively that the treatment has clinical benefit in delaying disease progression. The new, larger trials are intended to demonstrate a delay in disease progression and validate the use of blood-test markers of disease progression for studying an immune-based treatment.
AR DOC: Augmented reality documentaries
DEFF Research Database (Denmark)
Vistisen, Peter
2014-01-01
Augmented Reality Documentaries (AR DOC) er et ’lille’ Shareplay projekt (ansøgte midler augmented reality cross media løsninger, til at skabe engagerende publikumsformidling...... indenfor oplevelsesindustrien. Projektet har genereret ny viden omkring, hvordan fysisk og digital formidling kan understøttes via Augmented Reality som formidlingsformat....
[Immunogenicity of biosimilars].
van Aerts, L A G J M; Franken, A A M; Leufkens, H G M
2016-01-01
Biosimilars of more complex recombinant protein drugs, such as monoclonal antibodies and fusion proteins, are entering the market. The manufacturer should demonstrate that its product does not show any relevant differences in terms of quality characteristics, biological activity, safety and efficacy compared to the reference product, as outlined in EMA guidelines. This should be established with an extensive comparability exercise. One aspect that is subject to particular scrutiny is the immunogenicity of the biosimilar and the reference medicinal product. For three cases, one etanercept and two infliximab biosimilars, we describe how data are assessed and an opinion is reached by authorities. Not in all cases unanimity exists whether all remaining uncertainties on biosimilarity have been resolved satisfactorily before marketing authorisation. The Dutch Medicines Evaluation Board therefore emphasises that even after marketing authorisation, biosimilars and other biologicals should be properly monitored.
Posttranslational Modifications and the Immunogenicity of Biotherapeutics
Directory of Open Access Journals (Sweden)
Roy Jefferis
2016-01-01
Full Text Available Whilst the amino acid sequence of a protein is determined by its gene sequence, the final structure and function are determined by posttranslational modifications (PTMs, including quality control (QC in the endoplasmic reticulum (ER and during passage through the Golgi apparatus. These processes are species and cell specific and challenge the biopharmaceutical industry when developing a production platform for the generation of recombinant biologic therapeutics. Proteins and glycoproteins are also subject to chemical modifications (CMs both in vivo and in vitro. The individual is naturally tolerant to molecular forms of self-molecules but nonself variants can provoke an immune response with the generation of anti-drug antibodies (ADA; aggregated forms can exhibit enhanced immunogenicity and QC procedures are developed to avoid or remove them. Monoclonal antibody therapeutics (mAbs are a special case because their purpose is to bind the target, with the formation of immune complexes (ICs, a particular form of aggregate. Such ICs may be removed by phagocytic cells that have antigen presenting capacity. These considerations may frustrate the possibility of ameliorating the immunogenicity of mAbs by rigorous exclusion of aggregates from drug product. Alternate strategies for inducing immunosuppression or tolerance are discussed.
Cai, Yi; Tsai, Hsing-Chen; Yen, Ray-Whay Chiu; Zhang, Yang W; Kong, Xiangqian; Wang, Wei; Xia, Limin; Baylin, Stephen B
2017-04-01
Reversing DNA methylation abnormalities and associated gene silencing, through inhibiting DNA methyltransferases (DNMTs) is an important potential cancer therapy paradigm. Maximizing this potential requires defining precisely how these enzymes maintain genome-wide, cancer-specific DNA methylation. To date, there is incomplete understanding of precisely how the three DNMTs, 1, 3A, and 3B, interact for maintaining DNA methylation abnormalities in cancer. By combining genetic and shRNA depletion strategies, we define not only a dominant role for DNA methyltransferase 1 (DNMT1) but also distinct roles of 3A and 3B in genome-wide DNA methylation maintenance. Lowering DNMT1 below a threshold level is required for maximal loss of DNA methylation at all genomic regions, including gene body and enhancer regions, and for maximally reversing abnormal promoter DNA hypermethylation and associated gene silencing to reexpress key genes. It is difficult to reach this threshold with patient-tolerable doses of current DNMT inhibitors (DNMTIs). We show that new approaches, like decreasing the DNMT targeting protein, UHRF1, can augment the DNA demethylation capacities of existing DNA methylation inhibitors for fully realizing their therapeutic potential. © 2017 Cai et al.; Published by Cold Spring Harbor Laboratory Press.
Chicken IgY Fc expressed by Eimeria mitis enhances the immunogenicity of E. mitis.
Qin, Mei; Tang, Xinming; Yin, Guangwen; Liu, Xianyong; Suo, Jingxia; Tao, Geru; Ei-Ashram, Saeed; Li, Yuan; Suo, Xun
2016-03-21
Eimeria species are obligate intracellular apicomplexan parasites, causing great economic losses in the poultry industry. Currently wild-and attenuated- type anticoccidial vaccines are used to control coccidiosis. However, their use in fast growing broilers is limited by vaccination side effects caused by medium and/or low immunogenic Eimeria spp. There is, therefore, a need for a vaccine with high immunogenicity for broilers. The avian yolk sac IgY Fc is the avian counterpart of the mammalian IgG Fc, which enhances immunogenicity of Fc-fusion proteins. Here, we developed a stable transgenic Eimeria mitis expressing IgY Fc (Emi.chFc) and investigated whether the avian IgY Fc fragment enhances the immunogenicity of E. mitis. Two-week-old broilers were immunized with either Emi.chFc or wild type Eimeria and challenged with wild type E. mitis to analyze the protective properties of transgenic Emi.chFc. Chickens immunized with Emi.chFc had significantly lower oocyst output, in comparison with PBS, mock control (transgenic E. mitis expressing HA1 from H9N2 avian influenza virus) and wildtype E. mitis immunized groups after challenge, indicating that IgY Fc enhanced the immunogenicity of E. mitis. Our findings suggest that IgY Fc-expressing Eimeria may be a better coccidiosis vaccine, and transgenic Eimeria expressing Fc-fused exogenous antigens may be used as a novel vaccine-delivery vehicle against a wide variety of pathogens.
An immunochemical approach to the study of DNA damage and repair
International Nuclear Information System (INIS)
Wallace, S.S.; Erlanger, B.F.
1992-05-01
The overall objective of this project has been to develop immunochemical methods to quantitate unique DNA base damages in order to facilitate studies on radiation-induced damage production and repair. Specifically, we have been using antibodies raised to damaged bases to quantitate unique lesions in model systems in order to evaluate their potential biological consequences. Our approach has been to synthesize modified nucleotides or nucleosides, conjugate them to protein carriers, and use the conjugates as immunogens in rabbits or to prepare monoclonal antibodies. We have been studying damages that are stable radiolysis products found in X-irradiated DNA and thus of potential biological consequence. Our aim is to build an in vitro and in vivo data base on the interactions between model DNA lesions and such cellular enzymes as DNA polymerases and repair endonucleases. Initial studies have focused on pyrimidine ring saturation products (thymine glycol.and dihydrothymine), products resulting from ring fragmentation or base loss (urea, Β-ureidoisobutyric acid, abasic sites), 7-hydro-8-oxopurines, and more recently, cytosine radiolysis products. These modified bases serve as useful models for examining the potential lethal and/or mutagenic (carcinogenic) effects of the products of DNA radiolysis
Crime Scenes as Augmented Reality
DEFF Research Database (Denmark)
Sandvik, Kjetil
2010-01-01
Using the concept of augmented reality, this article will investigate how places in various ways have become augmented by means of different mediatization strategies. Augmentation of reality implies an enhancement of the places' emotional character: a certain mood, atmosphere or narrative surplus......, physical damage: they are all readable and interpretable signs. As augmented reality the crime scene carries a narrative which at first is hidden and must be revealed. Due to the process of investigation and the detective's ability to reason and deduce, the crime scene as place is reconstructed as virtual...
Field Evaluation of Immunogenicity of Five Commercial Vaccines ...
African Journals Online (AJOL)
Field Evaluation of Immunogenicity of Five Commercial Vaccines Against Newcastle Disease in Poultry Farms in Ibadan, Nigeria. ... The PDF file you selected should load here if your Web browser has a PDF reader plug-in installed (for example, a recent version of Adobe Acrobat Reader). If you would like more information ...
Meningococcal B vaccine. An immunogenic vaccine possibly useful during outbreaks.
2014-09-01
Invasive meningococcal infections can be life-threatening and cause severe sequelae. Antibiotic therapy is only partially effective. Bexsero is the first meningococcal B vaccine to be approved in the European Union. It contains four capsular antigens from various strains of group B meningococci. Clinical trials of this meningococcal B vaccine did not assess clinical protection. Two immunogenicity studies in adults, one in adolescents and six in infants, are available. They established the immunogenicity of the meningococcal B vaccine, determined age-appropriate vaccination schedules, and verified that concomitant administration of other vaccines did not undermine its immunogenicity. In the absence of relevant clinical trials, an in vitro study showed that sera from vaccinated individuals were likely to have bactericidal activity against 85% of 200 invasive meningococcal B strains isolated in France in 2007-2008. The meningococcal B vaccine provoked local adverse effects in most vaccinees, including local erythema, induration and pain. Fever occurred in about half of vaccinated children. Six cases of Kawasaki syndrome have been reported in children who received the vaccine, compared to only one case in control groups. In practice, the harm-benefit balance of this meningococcal B vaccine justify using it during outbreaks, provided the outbreak strain is covered by the vaccine antigens. Vaccinees should be enrolled in studies designed to evaluate clinical efficacy and to better determine the risk of Kawasaki syndrome.
Dealing with immunogenicity of biologicals: assessment and clinical relevance
Wolbink, Gerrit J.; Aarden, Lucien A.; Dijkmans, B. A. C.
2009-01-01
PURPOSE OF REVIEW: In the last decade, biologicals revolutionized rheumatology. An increasing number of patients benefit from biotherapeuticals. However, some patients do not respond to treatment and others lose their response after a certain time. Immunogenicity is one of the factors linked to
Trial Watch: Immunogenic cell death inducers for anticancer chemotherapy.
Pol, Jonathan; Vacchelli, Erika; Aranda, Fernando; Castoldi, Francesca; Eggermont, Alexander; Cremer, Isabelle; Sautès-Fridman, Catherine; Fucikova, Jitka; Galon, Jérôme; Spisek, Radek; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo
2015-04-01
The term "immunogenic cell death" (ICD) is now employed to indicate a functionally peculiar form of apoptosis that is sufficient for immunocompetent hosts to mount an adaptive immune response against dead cell-associated antigens. Several drugs have been ascribed with the ability to provoke ICD when employed as standalone therapeutic interventions. These include various chemotherapeutics routinely employed in the clinic (e.g., doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin) as well as some anticancer agents that are still under preclinical or clinical development (e.g., some microtubular inhibitors of the epothilone family). In addition, a few drugs are able to convert otherwise non-immunogenic instances of cell death into bona fide ICD, and may therefore be employed as chemotherapeutic adjuvants within combinatorial regimens. This is the case of cardiac glycosides, like digoxin and digitoxin, and zoledronic acid. Here, we discuss recent developments on anticancer chemotherapy based on ICD inducers.
Directory of Open Access Journals (Sweden)
Nina G. Heredia-Sandoval
2016-08-01
Full Text Available Gluten-related diseases are a range of inflammatory disorders of the small intestine, characterized by an adverse response to gluten ingestion; therefore, the treatment is a gluten withdrawal. In spite of the increased market of gluten-free products, widely available breads with high acceptability are still missing due to the technological challenge of substituting the special gluten properties. Instead of using alternative ingredients for baking, some attempts have been done to decrease gluten immunogenicity by its enzymatic degradation with microbial proteases. Although the gluten immunogenicity reduction has been reached to an acceptable level, some quality parameters of the products are affected. This review focus on the use of microbial peptidases to prepare less immunogenic baked goods and their effect on product quality.
Heredia-Sandoval, Nina G; Valencia-Tapia, Maribel Y; Calderón de la Barca, Ana M; Islas-Rubio, Alma R
2016-08-30
Gluten-related diseases are a range of inflammatory disorders of the small intestine, characterized by an adverse response to gluten ingestion; therefore, the treatment is a gluten withdrawal. In spite of the increased market of gluten-free products, widely available breads with high acceptability are still missing due to the technological challenge of substituting the special gluten properties. Instead of using alternative ingredients for baking, some attempts have been done to decrease gluten immunogenicity by its enzymatic degradation with microbial proteases. Although the gluten immunogenicity reduction has been reached to an acceptable level, some quality parameters of the products are affected. This review focus on the use of microbial peptidases to prepare less immunogenic baked goods and their effect on product quality.
Directory of Open Access Journals (Sweden)
Yanming Wang
2015-06-01
Full Text Available Uncontrolled immune responses to intracellular DNA have been shown to induce autoimmune diseases. Homeostasis regulation of immune responses to cytosolic DNA is critical for limiting the risk of autoimmunity and survival of the host. Here, we report that the E3 ubiquitin ligase tripartite motif protein 30α (TRIM30α was induced by herpes simplex virus type 1 (HSV-1 infection in dendritic cells (DCs. Knockdown or genetic ablation of TRIM30α augmented the type I IFNs and interleukin-6 response to intracellular DNA and DNA viruses. Trim30α-deficient mice were more resistant to infection by DNA viruses. Biochemical analyses showed that TRIM30α interacted with the stimulator of interferon genes (STING, which is a critical regulator of the DNA-sensing response. Overexpression of TRIM30α promoted the degradation of STING via K48-linked ubiquitination at Lys275 through a proteasome-dependent pathway. These findings indicate that E3 ligase TRIM30α is an important negative-feedback regulator of innate immune responses to DNA viruses by targeting STING.
Sritrakul, Tepyuda; Nitipan, Supachai; Wajjwalku, Worawidh; La-Ard, Anchalee; Suphatpahirapol, Chattip; Petkarnjanapong, Wimol; Ongphiphadhanakul, Boonsong; Prapong, Siriwan
2017-11-01
Leptospirosis is an important zoonotic disease, and the major outbreak of this disease in Thailand in 1999 was due largely to the Leptospira borgpetersenii serovar Sejroe. Identification of the leucine-rich repeat (LRR) LBJ_2271 protein containing immunogenic epitopes and the discovery of the LBJ_2271 ortholog in Leptospira serovar Sejroe, KU_Sej_R21_2271, led to further studies of the antigenic immune properties of KU_Sej_LRR_2271. The recombinant hybrid (rh) protein was created and expressed from a hybrid PCR fragment of KU_Sej_R21_2271 fused with DNA encoding the LBJ_2271 signal sequence for targeting protein as a membrane-anchoring protein. The fusion DNA was cloned into pET160/GW/D-TOPO® to form the pET160_hKU_R21_2271 plasmid. The plasmid was used to express the rhKU_Sej_LRR_2271 protein in Escherichia coli BL21 Star™ (DE3). The expressed protein was immunologically detected by Western blotting and immunoreactivity detection with hyperimmune sera, T cell epitope prediction by HLA allele and epitope peptide binding affinity, and potential T cell reactivity analysis. The immunogenic epitopes of the protein were evaluated and verified by HLA allele and epitope peptide complex structure molecular docking. Among fourteen best allele epitopes of this protein, binding affinity values of 12 allele epitopes remained unchanged compared to LBJ_2271. Two epitopes for alleles HLA-A0202 and -A0301 had higher IC 50 values, while T cell reactivity values of these peptides were better than values from LBJ_2271 epitopes. Eight of twelve epitope peptides had positive T-cell reactivity scores. Although the molecular docking of two epitopes, 3FPLLKEFLV11/47FPLLKEFLV55 and 50KLSTVPEGV58, into an HLA-A0202 model revealed a good fit in the docked structures, 50KLSTVPEGV58 and 94KLSTVPEEV102 are still considered as the proteins' best epitopes for allele HLA-A0202. The results of this study showed that rhKU_Sej_LRR_2271 protein contained natural immunological properties that should
Artificial Intelligence, DNA Mimicry, and Human Health.
Stefano, George B; Kream, Richard M
2017-08-14
The molecular evolution of genomic DNA across diverse plant and animal phyla involved dynamic registrations of sequence modifications to maintain existential homeostasis to increasingly complex patterns of environmental stressors. As an essential corollary, driver effects of positive evolutionary pressure are hypothesized to effect concerted modifications of genomic DNA sequences to meet expanded platforms of regulatory controls for successful implementation of advanced physiological requirements. It is also clearly apparent that preservation of updated registries of advantageous modifications of genomic DNA sequences requires coordinate expansion of convergent cellular proofreading/error correction mechanisms that are encoded by reciprocally modified genomic DNA. Computational expansion of operationally defined DNA memory extends to coordinate modification of coding and previously under-emphasized noncoding regions that now appear to represent essential reservoirs of untapped genetic information amenable to evolutionary driven recruitment into the realm of biologically active domains. Additionally, expansion of DNA memory potential via chemical modification and activation of noncoding sequences is targeted to vertical augmentation and integration of an expanded cadre of transcriptional and epigenetic regulatory factors affecting linear coding of protein amino acid sequences within open reading frames.
Comparative immunogenicity of local and imported infectious bursal ...
African Journals Online (AJOL)
A comparative immunogenicity and efficacy study of local and imported infectious bursal disease (IBD) vaccines administered to chicks (cockerels) at varying regimes (10 and 18, 10 and 28, 14 and 35 days of age) was carried out. The test birds were challenged seven days after the booster dose of the IBD vaccine by ...
Illiano, Elena; Bissa, Massimiliano; Paolini, Francesca; Zanotto, Carlo; De Giuli Morghen, Carlo; Franconi, Rosella; Radaelli, Antonia; Venuti, Aldo
2016-10-02
The therapeutic antitumor potency of a prime-boost vaccination strategy was explored, based on the mutated, nontransforming forms of the E6 (E6 F47R ) and E7 (E7 GGG ) oncogenes of Human Papilloma Virus type 16 (HPV16), fused to the Potato virus X (PVX) coat protein (CP) sequence. Previous data showed that CP fusion improves the immunogenicity of tumor-associated antigens and may thus increase their efficacy. After verifying the correct expression of E6 F47R CP and E7 GGG CP inserted into DNA and Fowlpox virus recombinants by Western blotting and immunofluorescence, their combined use was evaluated for therapy in a pre-clinical mouse model of HPV16-related tumorigenicity. Immunization protocols were applied using homologous (DNA/DNA) or heterologous (DNA/Fowlpox) prime-boost vaccine regimens. The humoral immune responses were determined by ELISA, and the therapeutic efficacy evaluated by the delay in tumor appearance and reduced tumor volume after inoculation of syngeneic TC-1* tumor cells. Homologous DNA/DNA genetic vaccines were able to better delay tumor appearance and inhibit tumor growth when DNAE6 F47R CP and DNAE7 GGG CP were administered in combination. However, the heterologous DNA/Fowlpox vaccination strategy was able to delay tumor appearance in a higher number of animals when E6 F47R CP and in particular E7 GGG CP were administered alone. Copyright © 2016 Elsevier B.V. All rights reserved.
Berryman, Donna R
2012-01-01
Augmented reality is a technology that overlays digital information on objects or places in the real world for the purpose of enhancing the user experience. It is not virtual reality, that is, the technology that creates a totally digital or computer created environment. Augmented reality, with its ability to combine reality and digital information, is being studied and implemented in medicine, marketing, museums, fashion, and numerous other areas. This article presents an overview of augmented reality, discussing what it is, how it works, its current implementations, and its potential impact on libraries.
Gong, Xin; Yin, He; Shi, Yuhua; He, Xiaoqiu; Yu, Yongjiao; Guan, Shanshan; Kuai, Ziyu; Haji, Nasteha M; Haji, Nafisa M; Kong, Wei; Shan, Yaming
2016-05-25
The ectodomain of the influenza A virus (IAV) hemagglutinin (HA) stem is highly conserved across strains and has shown promise as a universal influenza vaccine in a mouse model. In this study, potential B-cell epitopes were found through sequence alignment and epitope prediction in a stem fragment, HA2:90-105, which is highly conserved among virus subtypes H1, H3 and B. A norovirus (NoV) P particle platform was used to express the HA2:90-105 sequences from subtypes H1, H3 and B in loops 1, 2 and 3 of the protrusion (P) domain, respectively. Through mouse immunization and microneutralization assays, the immunogenicity and protective efficacy of the chimeric NoV P particle (trivalent HA2-PP) were tested against infection with three subtypes (H1N1, H3N2 and B) of IAV in Madin-Darby canine kidney cells. The protective efficacy of the trivalent HA2-PP was also evaluated preliminarily in vivo by virus challenge in the mouse model. The trivalent HA2-PP immunogen induced significant IgG antibody responses, which could be enhanced by a virus booster vaccination. Moreover, the trivalent HA2-PP immunogen also demonstrated in vitro neutralization of the H3 and B viruses, and in vivo protection against the H3 virus. Our results support the notion that a broadly protective vaccine approach using an HA2-based NoV P particle platform can provide cross-protection against challenge viruses of different IAV subtypes. The efficacy of the immunogen should be further enhanced for practicality, and a better understanding of the protective immune mechanism will be critical for the development of HA2-based multivalent vaccines.
Directory of Open Access Journals (Sweden)
Liu Xiangtao
2011-02-01
Full Text Available Abstract Background Foot-and-mouth disease (FMD is a highly contagious disease of livestock which causes severe economic loss in cloven-hoofed animals. Vaccination is still a major strategy in developing countries to control FMD. Currently, inactivated vaccine of FMDV has been used in many countries with limited success and safety concerns. Development of a novel effective vaccine is must. Methods In the present study, two recombinant pseudotype baculoviruses, one expressing the capsid of foot-and-mouth disease virus (FMDV under the control of a cytomegalovirus immediate early enhancer/promoter (CMV-IE, and the other the caspid plus a T-cell immunogen coding region under a CAG promoter were constructed, and their expression was characterized in mammalian cells. In addition, their immunogenicity in a mouse model was investigated. The humoral and cell-mediated immune responses induced by pseudotype baculovirus were compared with those of inactivated vaccine. Results Indirect immunofluorescence assay (IFA and indirect sandwich-ELISA (IS-ELISA showed both recombinant baculoviruses (with or without T-cell epitopes were transduced efficiently and expressed target proteins in BHK-21 cells. In mice, intramuscular inoculation of recombinants with 1 × 109 or 1 × 1010 PFU/mouse induced the production of FMDV-specific neutralizing antibodies and gamma interferon (IFN-γ. Furthermore, recombinant baculovirus with T-cell epitopes had better immunogenicity than the recombinant without T-cell epitopes as demonstrated by significantly enhanced IFN-γ production (P P Conclusions These results indicate that pseudotype baculovirus-mediated gene delivery could be a alternative strategy to develop a new generation of vaccines against FMDV infection.
Use of Augmented Reality in Education
Jeřábek, Tomáš
2014-01-01
This thesis deals with phenomena of augmented reality in context of didactics. The thesis aims to define augmented reality in conceptual and content area and focuses on augmented reality in the structure of educational tools and identification of its functions and use from the didactical standpoint. The thesis characterizes augmented reality as a specific technological-perceptual concept and establishes a system of perceptual, technological and resulting aspects that reflect important paramet...
Directory of Open Access Journals (Sweden)
Gilbert Greub
Full Text Available BACKGROUND: With the availability of new generation sequencing technologies, bacterial genome projects have undergone a major boost. Still, chromosome completion needs a costly and time-consuming gap closure, especially when containing highly repetitive elements. However, incomplete genome data may be sufficiently informative to derive the pursued information. For emerging pathogens, i.e. newly identified pathogens, lack of release of genome data during gap closure stage is clearly medically counterproductive. METHODS/PRINCIPAL FINDINGS: We thus investigated the feasibility of a dirty genome approach, i.e. the release of unfinished genome sequences to develop serological diagnostic tools. We showed that almost the whole genome sequence of the emerging pathogen Parachlamydia acanthamoebae was retrieved even with relatively short reads from Genome Sequencer 20 and Solexa. The bacterial proteome was analyzed to select immunogenic proteins, which were then expressed and used to elaborate the first steps of an ELISA. CONCLUSIONS/SIGNIFICANCE: This work constitutes the proof of principle for a dirty genome approach, i.e. the use of unfinished genome sequences of pathogenic bacteria, coupled with proteomics to rapidly identify new immunogenic proteins useful to develop in the future specific diagnostic tests such as ELISA, immunohistochemistry and direct antigen detection. Although applied here to an emerging pathogen, this combined dirty genome sequencing/proteomic approach may be used for any pathogen for which better diagnostics are needed. These genome sequences may also be very useful to develop DNA based diagnostic tests. All these diagnostic tools will allow further evaluations of the pathogenic potential of this obligate intracellular bacterium.
Safety and immunogenicity of two Haemophilus influenzae type b ...
African Journals Online (AJOL)
Objectives. Haemophilus influenzae type b (Hib) infection remains a major public health problem inthe developing world. We evaluated the safety and immunogenicity of a new PRP-CRM197 conjugate Hib vaccine (Vaxem Hib, Chiron Vacdnes), compared with theHibTITER vaccine (WyethLederle Vaccines), following the ...
Safety and immunogenicity of a CRM or TT conjugated meningococcal vaccine in healthy toddlers.
Bona, Gianni; Castiglia, Paolo; Zoppi, Giorgio; de Martino, Maurizio; Tasciotti, Annaelisa; D'Agostino, Diego; Han, Linda; Smolenov, Igor
2016-06-17
MenACWY-CRM (Menveo(®); GlaxoSmithKline) and MenACWY-TT (Nimenrix(®); Pfizer) are two meningococcal vaccines licensed in the European Union for use in both children and adults. While both vaccines target meningococcal serogroups A, C, W and Y, immunogenicity and reactogenicity of these quadrivalent meningococcal conjugate vaccines may differ due to differences in formulation processes and chemical structure. Yet data on the comparability of these two vaccines are limited. The reactogenicity and immunogenicity of one dose of either MenACWY-CRM or MenACWY-TT were evaluated in healthy toddlers aged 12-15 months. Immunogenicity was assessed using serum bactericidal antibody assays (SBA) with human (hSBA) and rabbit (rSBA) complement. A total of 202 children aged 12-15 months were enrolled to receive one dose of MenACWY-CRM or MenACWY-TT. Similar numbers of subjects reported solicited reactions within 7 days following either vaccination. Tenderness at the injection site was the most common local reaction. Systemic reactions reported were similar for both vaccines and mostly mild to moderate in severity: irritability, sleepiness and change in eating habits were most commonly reported. Immunogenicity at 1 month post-vaccination was generally comparable for both vaccines across serogroups. At 6 months post-vaccination antibody persistence against serogroups C, W, and Y was substantial for both vaccines, as measured by both assay methodologies. For serogroup A, hSBA titers declined in both groups, while rSBA titers remained high. Despite differences in composition, the MenACWY-CRM and MenACWY-TT vaccines have comparable reactogenicity and immunogenicity profiles. Immediate immune responses and short-term antibody persistence were largely similar between groups. Both vaccines were well-tolerated and no safety concerns were identified. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Hacker, Ulrich T; Schildhauer, Ines; Barroso, Margarita Céspedes; Kofler, David M; Gerner, Franz M; Mysliwietz, Josef; Buening, Hildegard; Hallek, Michael; King, Susan B S
2006-05-01
The modulated expression of MHC class I on tumour tissue is well documented. Although the effect of MHC class I expression on the tumorigenicity and immunogenicity of MHC class I negative tumour cell lines has been rigorously studied, less is known about the validity of gene transfer and selection in cell lines with a mixed MHC class I phenotype. To address this issue we identified a C26 cell subline that consists of distinct populations of MHC class I (H-2D/K) positive and negative cells. Transient transfection experiments using liposome-based transfer showed a lower transgene expression in MHC class I negative cells. In addition, MHC class I negative cells were more sensitive to antibiotic selection. This led to the generation of fully MHC class I positive cell lines. In contrast to C26 cells, all transfectants were rejected in vivo and induced protection against the parental tumour cells in rechallenge experiments. Tumour cell specificity of the immune response was demonstrated in in vitro cytokine secretion and cytotoxicity assays. Transfectants expressing CD40 ligand and hygromycin phosphotransferase were not more immunogenic than cells expressing hygromycin resistance alone. We suggest that the MHC class I positive phenotype of the C26 transfectants had a bearing on their immunogenicity, because selected MHC class I positive cells were more immunogenic than parental C26 cells and could induce specific anti-tumour immune responses. These data demonstrate that the generation of tumour cell transfectants can lead to the selection of subpopulations that show an altered phenotype compared to the parental cell line and display altered immunogenicity independent of selection marker genes or other immune modulatory genes. Our results show the importance of monitoring gene transfer in the whole tumour cell population, especially for the evaluation of in vivo therapies targeted to heterogeneous tumour cell populations.
Bayesian Alternation During Tactile Augmentation
Directory of Open Access Journals (Sweden)
Caspar Mathias Goeke
2016-10-01
Full Text Available A large number of studies suggest that the integration of multisensory signals by humans is well described by Bayesian principles. However, there are very few reports about cue combination between a native and an augmented sense. In particular, we asked the question whether adult participants are able to integrate an augmented sensory cue with existing native sensory information. Hence for the purpose of this study we build a tactile augmentation device. Consequently, we compared different hypotheses of how untrained adult participants combine information from a native and an augmented sense. In a two-interval forced choice (2 IFC task, while subjects were blindfolded and seated on a rotating platform, our sensory augmentation device translated information on whole body yaw rotation to tactile stimulation. Three conditions were realized: tactile stimulation only (augmented condition, rotation only (native condition, and both augmented and native information (bimodal condition. Participants had to choose one out of two consecutive rotations with higher angular rotation. For the analysis, we fitted the participants’ responses with a probit model and calculated the just notable difference (JND. Then we compared several models for predicting bimodal from unimodal responses. An objective Bayesian alternation model yielded a better prediction (χred2 = 1.67 than the Bayesian integration model (χred2= 4.34. Slightly higher accuracy showed a non-Bayesian winner takes all model (χred2= 1.64, which either used only native or only augmented values per subject for prediction. However the performance of the Bayesian alternation model could be substantially improved (χred2= 1.09 utilizing subjective weights obtained by a questionnaire. As a result, the subjective Bayesian alternation model predicted bimodal performance most accurately among all tested models. These results suggest that information from augmented and existing sensory modalities in
DEFF Research Database (Denmark)
Kjærgaard, Hanne Wacher; Kjeldsen, Lars Peter Bech; Rahn, Annette
2015-01-01
This chapter describes the use of iPad-facilitated application of augmented reality in the teaching of highly complex anatomical and physiological subjects in the training of nurses at undergraduate level. The general aim of the project is to investigate the potentials of this application in terms...... of making the complex content and context of these subjects more approachable to the students through the visualization made possible through the use of this technology. A case study is described in this chapter. Issues and factors required for the sustainable use of the mobile-facilitated application...... of augmented reality are discussed....
Affordances in Mobile Augmented Reality Applications
Gjøsæter, Tor
2014-01-01
This paper explores the affordances of augmented reality content in a mobile augmented reality application. A user study was conducted by performing a multi-camera video recording of seven think aloud sessions. The think aloud sessions consisted of individual users performing tasks, exploring and experiencing a mobile augmented reality (MAR) application we developed for the iOS platform named ARad. We discuss the instrumental affordances we observed when users interacted with augmented realit...
Hoogeslag, Roy A G; Brouwer, Reinoud W; Huis In 't Veld, Rianne; Stephen, Joanna M; Amis, Andrew A
2018-02-03
There is a lack of objective evidence investigating how previous non-augmented ACL suture repair techniques and contemporary augmentation techniques in ACL suture repair restrain anterior tibial translation (ATT) across the arc of flexion, and after cyclic loading of the knee. The purpose of this work was to test the null hypotheses that there would be no statistically significant difference in ATT after non-, static- and dynamic-augmented ACL suture repair, and they will not restore ATT to normal values across the arc of flexion of the knee after cyclic loading. Eleven human cadaveric knees were mounted in a test rig, and knee kinematics from 0° to 90° of flexion were recorded by use of an optical tracking system. Measurements were recorded without load and with 89-N tibial anterior force. The knees were tested in the following states: ACL-intact, ACL-deficient, non-augmented suture repair, static tape augmentation and dynamic augmentation after 10 and 300 loading cycles. Only static tape augmentation and dynamic augmentation restored ATT to values similar to the ACL-intact state directly postoperation, and maintained this after cyclic loading. However, contrary to dynamic augmentation, the ATT after static tape augmentation failed to remain statistically less than for the ACL-deficient state after cyclic loading. Moreover, after cyclic loading, ATT was significantly less with dynamic augmentation when compared to static tape augmentation. In contrast to non-augmented ACL suture repair and static tape augmentation, only dynamic augmentation resulted in restoration of ATT values similar to the ACL-intact knee and decreased ATT values when compared to the ACL-deficient knee immediately post-operation and also after cyclic loading, across the arc of flexion, thus allowing the null hypotheses to be rejected. This may assist healing of the ruptured ACL. Therefore, this study would support further clinical evaluation of dynamic augmentation of ACL repair.
Allotransplanted neurons used to repair peripheral nerve injury do not elicit overt immunogenicity.
Directory of Open Access Journals (Sweden)
Weimin Liu
Full Text Available A major problem hindering the development of autograft alternatives for repairing peripheral nerve injuries is immunogenicity. We have previously shown successful regeneration in transected rat sciatic nerves using conduits filled with allogeneic dorsal root ganglion (DRG cells without any immunosuppression. In this study, we re-examined the immunogenicity of our DRG neuron implanted conduits as a potential strategy to overcome transplant rejection. A biodegradable NeuraGen® tube was infused with pure DRG neurons or Schwann cells cultured from a rat strain differing from the host rats and used to repair 8 mm gaps in the sciatic nerve. We observed enhanced regeneration with allogeneic cells compared to empty conduits 16 weeks post-surgery, but morphological analyses suggest recovery comparable to the healthy nerves was not achieved. The degree of regeneration was indistinguishable between DRG and Schwann cell allografts although immunogenicity assessments revealed substantially increased presence of Interferon gamma (IFN-γ in Schwann cell allografts compared to the DRG allografts by two weeks post-surgery. Macrophage infiltration of the regenerated nerve graft in the DRG group 16 weeks post-surgery was below the level of the empty conduit (0.56 fold change from NG; p<0.05 while the Schwann cell group revealed significantly higher counts (1.29 fold change from NG; p<0.001. Major histocompatibility complex I (MHC I molecules were present in significantly increased levels in the DRG and Schwann cell allograft groups compared to the hollow NG conduit and the Sham healthy nerve. Our results confirmed previous studies that have reported Schwann cells as being immunogenic, likely due to MHC I expression. Nerve gap injuries are difficult to repair; our data suggest that DRG neurons are superior medium to implant inside conduit tubes due to reduced immunogenicity and represent a potential treatment strategy that could be preferable to the current gold
Augment-type two stage accelerator
International Nuclear Information System (INIS)
Ogino, Mutsuo; Azuma, Kingo.
1995-01-01
When a flying body accelerated by a gas gun at a first stage enters into an augment rail passing through an introduction tube, an ignition capacitor for initial plasmas is turned ON to apply a voltage between the augment rails. Subsequently, the accelerating gas present behind the flying body is formed into plasmas by a laser, to flow electric current from one of the inner augment rails → plasma armature → the other of the inner augment rails, and additionally accelerate the flying body by Lorentz force formed in this case. Since the plasmas are maintained in a state of higher density than the plasmas obtained by using all of the augment rails, the ignition capacitor for initial plasmas in switched to a power source. As a result, it is possible to flow the maximum current before the plasmas expand, and a large accelerating force and a high magnetic flux density are attained, to improve acceleration performance of the flying body. (N.H.)
Flügge, Tabea; Nelson, Katja; Nack, Claudia; Stricker, Andres; Nahles, Susanne
2015-04-01
This study identified the soft tissue changes of the alveolar ridge at different time points within 12 weeks after tooth extraction with and without socket augmentation. In 38 patients with single tooth extractions, 40 sockets were augmented and 39 extraction sockets were not augmented. At 2, 4, 6, 8 and 12 weeks impressions were taken and casts digitized with a laser scanner. The horizontal and vertical changes were compared between augmented and non-augmented sites. A p-value sockets were between 0.4 mm (2 weeks) and 0.8 mm (12 weeks). In non-augmented sockets changes of 0.7 mm (2 weeks) and of 1.0 mm (12 weeks) were demonstrated. The mean values differed significantly between the buccal and oral region (p sockets showed less resorption within 4 weeks after extraction compared to non-augmented sockets. Non-augmented sockets showed a continuous dimensional loss with a great variation over 12 weeks whereas augmented sockets had the highest degree of resorption between 4 and 6 weeks. At 12 weeks a comparable resorption in augmented and non-augmented sockets was observed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
The Five Immune Forces Impacting DNA-Based Cancer Immunotherapeutic Strategy
Directory of Open Access Journals (Sweden)
Suneetha Amara
2017-03-01
Full Text Available DNA-based vaccine strategy is increasingly realized as a viable cancer treatment approach. Strategies to enhance immunogenicity utilizing tumor associated antigens have been investigated in several pre-clinical and clinical studies. The promising outcomes of these studies have suggested that DNA-based vaccines induce potent T-cell effector responses and at the same time cause only minimal side-effects to cancer patients. However, the immune evasive tumor microenvironment is still an important hindrance to a long-term vaccine success. Several options are currently under various stages of study to overcome immune inhibitory effect in tumor microenvironment. Some of these approaches include, but are not limited to, identification of neoantigens, mutanome studies, designing fusion plasmids, vaccine adjuvant modifications, and co-treatment with immune-checkpoint inhibitors. In this review, we follow a Porter’s analysis analogy, otherwise commonly used in business models, to analyze various immune-forces that determine the potential success and sustainable positive outcomes following DNA vaccination using non-viral tumor associated antigens in treatment against cancer.
Augmented assessment as a means to augmented reality.
Bergeron, Bryan
2006-01-01
Rigorous scientific assessment of educational technologies typically lags behind the availability of the technologies by years because of the lack of validated instruments and benchmarks. Even when the appropriate assessment instruments are available, they may not be applied because of time and monetary constraints. Work in augmented reality, instrumented mannequins, serious gaming, and similar promising educational technologies that haven't undergone timely, rigorous evaluation, highlights the need for assessment methodologies that address the limitations of traditional approaches. The most promising augmented assessment solutions incorporate elements of rapid prototyping used in the software industry, simulation-based assessment techniques modeled after methods used in bioinformatics, and object-oriented analysis methods borrowed from object oriented programming.
Safety and immunogenicity of a live attenuated mumps vaccine
Liang, Yan; Ma, Jingchen; Li, Changgui; Chen, Yuguo; Liu, Longding; Liao, Yun; Zhang, Ying; Jiang, Li; Wang, Xuan-Yi; Che, Yanchun; Deng, Wei; Li, Hong; Cui, Xiaoyu; Ma, Na; Ding, Dong; Xie, Zhongping; Cui, Pingfang; Ji, Qiuyan; Wang, Jingjing; Zhao, Yuliang; Wang, Junzhi; Li, Qihan
2014-01-01
Background: Mumps, a communicable, acute and previously well-controlled disease, has had recent and occasional resurgences in some areas. Methods: A randomized, double-blind, controlled and multistep phase I study of an F-genotype attenuated mumps vaccine produced in human diploid cells was conducted. A total of 300 subjects were enrolled and divided into 4 age groups: 16–60 years, 5–16 years, 2–5 years and 8–24 months. The groups were immunized with one injection per subject. Three different doses of the F-genotype attenuated mumps vaccine, A (3.5 ± 0.25 logCCID50), B (4.25 ± 0.25 logCCID50) and C (5.0 ± 0.25 logCCID50), as well as a placebo control and a positive control of a licensed A-genotype vaccine (S79 strain) were used. The safety and immunogenicity of this vaccine were compared with those of the controls. Results: The safety evaluation suggested that mild adverse reactions were observed in all groups. No serious adverse event (SAE) was reported throughout the trial. The immunogenicity test showed a similar seroconversion rate of the neutralizing and ELISA antibody in the 2- to 5-year-old and 8- to 24-month-old groups compared with the seroconversion rate in the positive control. The GMT of the neutralizing anti-F-genotype virus antibodies in the vaccine groups was slightly higher than that in the positive control group. Conclusions: The F-genotype attenuated mumps vaccine evaluated in this clinical trial was demonstrated to be safe and have effective immunogenicity vs. control. PMID:24614759
Rup, B; Pallardy, M; Sikkema, D; Albert, T; Allez, M; Broet, P; Carini, C; Creeke, P; Davidson, J; De Vries, N; Finco, D; Fogdell-Hahn, A; Havrdova, E; Hincelin-Mery, A; C Holland, M; H Jensen, P E; Jury, E C; Kirby, H; Kramer, D; Lacroix-Desmazes, S; Legrand, J; Maggi, E; Maillère, B; Mariette, X; Mauri, C; Mikol, V; Mulleman, D; Oldenburg, J; Paintaud, G; R Pedersen, C; Ruperto, N; Seitz, R; Spindeldreher, S; Deisenhammer, F
2015-09-01
Biopharmaceuticals (BPs) represent a rapidly growing class of approved and investigational drug therapies that is contributing significantly to advancing treatment in multiple disease areas, including inflammatory and autoimmune diseases, genetic deficiencies and cancer. Unfortunately, unwanted immunogenic responses to BPs, in particular those affecting clinical safety or efficacy, remain among the most common negative effects associated with this important class of drugs. To manage and reduce risk of unwanted immunogenicity, diverse communities of clinicians, pharmaceutical industry and academic scientists are involved in: interpretation and management of clinical and biological outcomes of BP immunogenicity, improvement of methods for describing, predicting and mitigating immunogenicity risk and elucidation of underlying causes. Collaboration and alignment of efforts across these communities is made difficult due to lack of agreement on concepts, practices and standardized terms and definitions related to immunogenicity. The Innovative Medicines Initiative (IMI; www.imi-europe.org), ABIRISK consortium [Anti-Biopharmaceutical (BP) Immunization Prediction and Clinical Relevance to Reduce the Risk; www.abirisk.eu] was formed by leading clinicians, academic scientists and EFPIA (European Federation of Pharmaceutical Industries and Associations) members to elucidate underlying causes, improve methods for immunogenicity prediction and mitigation and establish common definitions around terms and concepts related to immunogenicity. These efforts are expected to facilitate broader collaborations and lead to new guidelines for managing immunogenicity. To support alignment, an overview of concepts behind the set of key terms and definitions adopted to date by ABIRISK is provided herein along with a link to access and download the ABIRISK terms and definitions and provide comments (http://www.abirisk.eu/index_t_and_d.asp). © 2015 British Society for Immunology.
Immunogenicity of Anti-TNF-α Biotherapies
DEFF Research Database (Denmark)
Bendtzen, Klaus
2015-01-01
% of patients do not respond and about 50% of those who do loose response with time. Furthermore, safety may be compromised by immunogenicity with the induction of anti-drug-antibodies (ADA). Assessment of drug pharmacokinetics and ADA is increasingly recognized as a requirement for safe and rational use...... article - and the accompanying article - is to discuss the reasons for recommending assessments of circulating drug and ADA levels in patients treated with anti-TNF biopharmaceuticals and to detail some of the methodological issues that obscure cost-effective and safer therapies....
Augmented Reality Using JavaScript
Hailemichael, Aida
2013-01-01
The project goal was to provide a mobile application, for a venue called Kulturhuset Karelia which is located in Tammisaari Finland. In this paper, the concept of Augmented Reality technology is briefly discussed along with the mobile application for the venue. The utilisation of JavaScript for creating Augmented reality content for mobile Augmented reality browser is also demonstrated. The application was created by using Architecht API which is Jacvascript library based on the Wikitude...
Bissa, Massimiliano; Pacchioni, Sole Maria; Zanotto, Carlo; De Giuli Morghen, Carlo; Illiano, Elena; Granucci, Francesca; Zanoni, Ivan; Broggi, Achille; Radaelli, Antonia
2013-12-26
The first-generation smallpox vaccine was based on live vaccinia virus (VV) and it successfully eradicated the disease worldwide. Therefore, it was not administered any more after 1980, as smallpox no longer existed as a natural infection. However, emerging threats by terrorist organisations has prompted new programmes for second-generation vaccine development based on attenuated VV strains, which have been shown to cause rare but serious adverse events in immunocompromised patients. Considering the closely related animal poxviruses that might also be used as bioweapons, and the increasing number of unvaccinated young people and AIDS-affected immunocompromised subjects, a safer and more effective smallpox vaccine is still required. New avipoxvirus-based vectors should improve the safety of conventional vaccines, and protect from newly emerging zoonotic orthopoxvirus diseases and from the threat of deliberate release of variola or monkeypox virus in a bioterrorist attack. In this study, DNA and fowlpox recombinants expressing the L1R, A27L, A33R and B5R genes were constructed and evaluated in a pre-clinical trial in mouse, following six prime/boost immunisation regimens, to compare their immunogenicity and protective efficacy against a challenge with the lethal VV IHD-J strain. Although higher numbers of VV-specific IFNγ-producing T lymphocytes were observed in the protected mice, the cytotoxic T-lymphocyte response and the presence of neutralising antibodies did not always correlate with protection. In spite of previous successful results in mice, rabbits and monkeys, where SIV/HIV transgenes were expressed by the fowlpox vector, the immune response elicited by these recombinants was low, and most of the mice were not protected. Copyright © 2013 Elsevier B.V. All rights reserved.
Augmented Reality for Multi-disciplinary Collaboration
Wang, Xiangyu; Rui,
2010-01-01
This chapter presents a framework for multi-disciplinary collaboration. Tangible Augmented Reality has been raised as one of suitable systems for design collaboration. Furthermore, it emphasizes the advantages of Tangible Augmented Reality to illustrate the needs for integrating the Tangible User Interfaces and Augmented Reality Systems.
Directory of Open Access Journals (Sweden)
Edward Maggio
2017-09-01
Full Text Available The increasing use of biotherapeutics across a growing spectrum of neoplastic, autoimmune, and inflammatory diseases has resulted in a corresponding increase in hypersensitivity reactions. The origins of anaphylaxis are often attributed to undefined intrinsic properties of the biotherapeutic protein itself, ignoring the broader potential negative contributions of functional excipients, in particular polyoxyethylene containing surfactants such as polysorbate 80 and polysorbate 20 (Tween 80 and Tween 20. These surfactants allow biotherapeutics to meet the stringent challenges of extended shelf-life, increased solubility, protein aggregation prevention, reduced administration volume, and satisfactory reconstitution properties in the case of lyophilized biotherapeutics. The potential negative impact of certain functional excipients on product performance characteristics such as anaphylaxis and immunogenicity is often overlooked. While regulatory authorities understandably focus heavily on comparable efficacy in evaluating biosimilars, similar efficacy does not necessarily imply a similar safety profile between the originator and biosimilar products. Both unwanted immunogenicity and anaphylaxis do comprise major components of safety assessment, however, few if any attempts are made to differentiate drug-related from excipient-related anaphylaxis. Replacement of anaphylactogenic and immunogenic functional excipients with equally effective but safer alternatives will allow biotherapeutic developers to differentiate their biotherapeutic, biosimilar, or biobetter from the large number of nearly identical competitor products, simultaneously providing a substantial commercial benefit as well as critical clinical benefits for all concerned – patients, physicians, and third party payers.
Protective immunity conferred by porcine circovirus 2 ORF2-based DNA vaccine in mice.
Sylla, Seydou; Cong, Yan-Long; Sun, Yi-Xue; Yang, Gui-Lian; Ding, Xue-Mei; Yang, Zhan-Qing; Zhou, Yu-Long; Yang, Minnan; Wang, Chun-Feng; Ding, Zhuang
2014-07-01
Post-weaning multisystemic wasting syndrome (PMWS) associated with porcine circovirus type 2 (PCV2) has caused the swine industry significant health challenges and economic damage. Although inactivated and subunit vaccines against PMWS have been used widely, so far no DNA vaccine is available. In this study, with the aim of exploring a new route for developing a vaccine against PCV2, the immunogenicity of a DNA vaccine was evaluated in mice. The pEGFP-N1 vector was used to construct a PCV2 Cap gene recombinant vaccine. To assess the immunogenicity of pEGFP-Cap, 80 BALB/c mice were immunized three times at 2 weekly intervals with pEGFP-Cap, LG-strain vaccine, pEGFP-N1 vector or PBS and then challenged with PCV2. IgG and cytokines were assessed by indirect ELISA and ELISA, respectively. Specimens stained with hematoxylin and eosin (HE) and immunohistochemistry (IHC) techniques were examined histopathologically. It was found that vaccination of the mice with the pEGFP-Cap induced solid protection against PCV2 infection through induction of highly specific serum IgG antibodies and cytokines (IFN-γ and IL-10), and a small PCV2 viral load. The mice treated with the pEGFP-Cap and LG-strain developed no histopathologically detectable lesions (HE stain) and IHC techniques revealed only a few positive cells. Thus, this study demonstrated that recombinant pEGFP-Cap substantially alleviates PCV2 infection in mice and provides evidence that a DNA vaccine could be an alternative to PCV2 vaccines against PMWS. © 2014 The Societies and Wiley Publishing Asia Pty Ltd.
Performance of a self-augmented railgun
International Nuclear Information System (INIS)
Burton, R.L.; Witherspoon, F.D.; Goldstein, S.A.
1991-01-01
The accelerating force of a railgun 1/2L'I 2 a can be increased by augmenting the self-induced magnetic field created by the armature current. Augmentation fields can be produced by external current coils or, as is done here, by shorting the railgun muzzle, and using the gun rails as the augmentation coil. Experimental results are presented for a 3.6-m railgun operated in this self-augmented mode, and effective inductance gradients are achieved which are as much as 9.3 times that of the unaugmented gun. A circuit model is presented which explains features of the measured shunt current and voltage. It is concluded that self-augmentation is an effective way to reduce ohmic heating in the armature of a railgun
Effects of gamma radiation and heat on immunogenicity and morphology of Salmonella typhimurium
International Nuclear Information System (INIS)
Santos Araujo, E. dos; Silva, D.M.
1979-01-01
Results are presented about immunogenicity of vaccines prepared from Salmonella typhimurium suspensions submitted to 0,55 MR and 1,10 MR of gamma radiation and heating at 60 0 C, (60 min) and at 100 0 C, (3 min) correlated with the cell morphology alterations observed at electron microscopy. The results of mouse-protection tests showed that prepared vaccines with 0,55 MR and with heating at 60 0 C, 60 min were identical and more efficient than the two other treatments. The electronmicrografies also showed one positive correlation between morphological alterations caused by the treatments and the immunogenicities. (Author) [pt
Tetteh, Sampson
2015-01-01
The vast majority of mobile technology today has developed over the past dec-ades. The thirst for information and communication has brought about high data transfer speed on modern mobile handset devices. This makes it possible for Augmented Reality to be used on mobile phones. Vaasa University of Applied Science, Technobothnia science resource center and Lumivaara Museum saw the importance of information and decided to embark on a pilot project where Augmented Reality will not be only us...
Janssen, George; Christis, Chantal; Kooy-Winkelaar, Yvonne; Edens, Luppo; Smith, Drew
2015-01-01
Background Due to the high proline content of gluten molecules, gastrointestinal proteases are unable to fully degrade them leaving large proline-rich gluten fragments intact, including an immunogenic 33-mer from α-gliadin and a 26-mer from γ-gliadin. These latter peptides can trigger pro-inflammatory T cell responses resulting in tissue remodeling, malnutrition and a variety of other complications. A strict lifelong gluten-free diet is currently the only available treatment to cope with gluten intolerance. Post-proline cutting enzymes have been shown to effectively degrade the immunogenic gluten peptides and have been proposed as oral supplements. Several existing digestive enzyme supplements also claim to aid in gluten degradation. Here we investigate the effectiveness of such existing enzyme supplements in comparison with a well characterized post-proline cutting enzyme, Prolyl EndoPeptidase from Aspergillus niger (AN-PEP). Methods Five commercially available digestive enzyme supplements along with purified digestive enzymes were subjected to 1) enzyme assays and 2) mass spectrometric identification. Gluten epitope degradation was monitored by 1) R5 ELISA, 2) mass spectrometric analysis of the degradation products and 3) T cell proliferation assays. Findings The digestive enzyme supplements showed comparable proteolytic activities with near neutral pH optima and modest gluten detoxification properties as determined by ELISA. Mass spectrometric analysis revealed the presence of many different enzymes including amylases and a variety of different proteases with aminopeptidase and carboxypeptidase activity. The enzyme supplements leave the nine immunogenic epitopes of the 26-mer and 33-mer gliadin fragments largely intact. In contrast, the pure enzyme AN-PEP effectively degraded all nine epitopes in the pH range of the stomach at much lower dose. T cell proliferation assays confirmed the mass spectrometric data. Conclusion Currently available digestive enzyme
Directory of Open Access Journals (Sweden)
George Janssen
Full Text Available Due to the high proline content of gluten molecules, gastrointestinal proteases are unable to fully degrade them leaving large proline-rich gluten fragments intact, including an immunogenic 33-mer from α-gliadin and a 26-mer from γ-gliadin. These latter peptides can trigger pro-inflammatory T cell responses resulting in tissue remodeling, malnutrition and a variety of other complications. A strict lifelong gluten-free diet is currently the only available treatment to cope with gluten intolerance. Post-proline cutting enzymes have been shown to effectively degrade the immunogenic gluten peptides and have been proposed as oral supplements. Several existing digestive enzyme supplements also claim to aid in gluten degradation. Here we investigate the effectiveness of such existing enzyme supplements in comparison with a well characterized post-proline cutting enzyme, Prolyl EndoPeptidase from Aspergillus niger (AN-PEP.Five commercially available digestive enzyme supplements along with purified digestive enzymes were subjected to 1 enzyme assays and 2 mass spectrometric identification. Gluten epitope degradation was monitored by 1 R5 ELISA, 2 mass spectrometric analysis of the degradation products and 3 T cell proliferation assays.The digestive enzyme supplements showed comparable proteolytic activities with near neutral pH optima and modest gluten detoxification properties as determined by ELISA. Mass spectrometric analysis revealed the presence of many different enzymes including amylases and a variety of different proteases with aminopeptidase and carboxypeptidase activity. The enzyme supplements leave the nine immunogenic epitopes of the 26-mer and 33-mer gliadin fragments largely intact. In contrast, the pure enzyme AN-PEP effectively degraded all nine epitopes in the pH range of the stomach at much lower dose. T cell proliferation assays confirmed the mass spectrometric data.Currently available digestive enzyme supplements are ineffective in
INTEGRATIVE AUGMENTATION OF STANDARDIZED MANAGEMENT SYSTEMS
Directory of Open Access Journals (Sweden)
Stanislav Karapetrovic
2008-03-01
Full Text Available The development, features and integrating abilities of different international standards related to management systems are discussed. A group of such standards that augment the performance of quality management systems in organizations is specifically focused on. The concept, characteristics and an illustrative example of one augmenting standard, namely ISO 10001, are addressed. Integration of standardized augmenting systems, both by themselves and within the overall management system, is examined. It is argued that, in research and practice alike, integrative augmentation represents the future of standardized quality and other management systems.
AUGMENTATION-RELATED BRAIN PLASTICITY
Directory of Open Access Journals (Sweden)
Giovanni eDi Pino
2014-06-01
Full Text Available Today, the anthropomorphism of the tools and the development of neural interfaces require reconsidering the concept of human-tools interaction in the framework of human augmentation. This review analyzes the plastic process that the brain undergoes when it comes into contact with augmenting artificial sensors and effectors and, on the other hand, the changes that the use of external augmenting devices produces in the brain.Hitherto, few studies investigated the neural correlates of augmentation, but clues on it can be borrowed from logically-related paradigms: sensorimotor training, cognitive enhancement, cross-modal plasticity, sensorimotor functional substitution, use and embodiment of tools.Augmentation modifies function and structure of a number of areas, i.e. primary sensory cortices shape their receptive fields to become sensitive to novel inputs. Motor areas adapt the neuroprosthesis representation firing-rate to refine kinematics. As for normal motor outputs, the learning process recruits motor and premotor cortices and the acquisition of proficiency decreases attentional recruitment, focuses the activity on sensorimotor areas and increases the basal ganglia drive on the cortex. Augmentation deeply relies on the frontoparietal network. In particular, premotor cortex is involved in learning the control of an external effector and owns the tool motor representation, while the intraparietal sulcus extracts its visual features. In these areas, multisensory integration neurons enlarge their receptive fields to embody supernumerary limbs. For operating an anthropomorphic neuroprosthesis, the mirror system is required to understand the meaning of the action, the cerebellum for the formation of its internal model and the insula for its interoception. In conclusion, anthropomorphic sensorized devices can provide the critical sensory afferences to evolve the exploitation of tools through their embodiment, reshaping the body representation and the
Confronting an Augmented Reality
Munnerley, Danny; Bacon, Matt; Wilson, Anna; Steele, James; Hedberg, John; Fitzgerald, Robert
2012-01-01
How can educators make use of augmented reality technologies and practices to enhance learning and why would we want to embrace such technologies anyway? How can an augmented reality help a learner confront, interpret and ultimately comprehend reality itself ? In this article, we seek to initiate a discussion that focuses on these questions, and…
Advanced Intellect-Augmentation Techniques.
Engelbart, D. C.
This progress report covers a two-year project which is part of a program that is exploring the value of computer aids in augmenting human intellectual capability. The background and nature of the program, its resources, and the activities it has undertaken are outlined. User experience in applying augmentation tools and techniques to various…
Listeriolysin o is strongly immunogenic independently of its cytotoxic activity.
Directory of Open Access Journals (Sweden)
Javier A Carrero
Full Text Available The presentation of microbial protein antigens by Major Histocompatibility Complex (MHC molecules is essential for the development of acquired immunity to infections. However, most biochemical studies of antigen processing and presentation deal with a few relatively inert non-microbial model antigens. The bacterial pore-forming toxin listeriolysin O (LLO is paradoxical in that it is cytotoxic at nanomolar concentrations as well as being the source of dominant CD4 and CD8 T cell epitopes following infection with Listeria monocytogenes. Here, we examined the relationship of LLO toxicity to its antigenicity and immunogenicity. LLO offered to antigen presenting cells (APC as a soluble protein, was presented to CD4 T cells at picomolar to femtomolar concentrations- doses 3000-7000-fold lower than free peptide. This presentation required a dose of LLO below the cytotoxic level. Mutations of two key tryptophan residues reduced LLO toxicity by 10-100-fold but had no effect on its presentation to CD4 T cells. Thus there was a clear dissociation between the cytotoxic properties of LLO and its very high antigenicity. Presentation of LLO to CD8 T cells was not as robust as that seen in CD4 T cells, but still occurred in the nanomolar range. APC rapidly bound and internalized LLO, then disrupted endosomal compartments within 4 hours of treatment, allowing endosomal contents to access the cytosol. LLO was also immunogenic after in vivo administration into mice. Our results demonstrate the strength of LLO as an immunogen to both CD4 and CD8 T cells.
Novel Augmentation Strategies in Major Depression
DEFF Research Database (Denmark)
Martiny, Klaus
2017-01-01
Hypothesis The hypotheses of all the four included studies share the common idea that it is possible to augment the effect of antidepressant drug treatment by applying different interventions and with each intervention attain a clinically meaningful better effect compared to a control condition...... and randomised to augmentation with either active or placebo matching pindolol tablets. In the PEMF study patients were continued on ongoing medication and randomised to augmentation with active or inactive (sham) 30 minutes daily PEMF treatment on weekdays. In the Chronos study all patients were treated...... The results from the Pindolol study showed that pindolol did not augment the effect of venlafaxine for the whole sample. However, for those patients classified as slow metabolizers, based on their O-desmethylvenlafaxine/venlafaxine ratio (ODV/V), pindolol did augment the antidepressant effect. For patients...
Augmented Reality for Science Education
DEFF Research Database (Denmark)
Brandt, Harald; Nielsen, Birgitte Lund; Georgsen, Marianne
Augmented reality (AR) holds great promise as a learning tool. So far, however, most research has looked at the technology itself – and AR has been used primarily for commercial purposes. As a learning tool, AR supports an inquiry-based approach to science education with a high level of student...... involvement. The AR-sci-project (Augmented Reality for SCIence education) addresses the issue of applying augmented reality in developing innovative science education and enhancing the quality of science teaching and learning....
Immunogenicity of virus-like particles containing modified goose parvovirus VP2 protein.
Chen, Zongyan; Li, Chuanfeng; Zhu, Yingqi; Wang, Binbin; Meng, Chunchun; Liu, Guangqing
2012-10-01
The major capsid protein VP2 of goose parvovirus (GPV) expressed using a baculovirus expression system (BES) assembles into virus-like particles (VLPs). To optimize VP2 gene expression in Sf9 cells, we converted wild-type VP2 (VP2) codons into codons that are more common in insect genes. This change greatly increased VP2 protein production in Sf9 cells. The protein generated from the codon-optimized VP2 (optVP2) was detected by immunoblotting and an indirect immunofluorescence assay (IFA). Transmission electron microscopy analysis revealed the formation of VLPs. These findings indicate that optVP2 yielded stable and high-quality VLPs. Immunogenicity assays revealed that the VLPs are highly immunogenic, elicit a high level of neutralizing antibodies and provide protection against lethal challenge. The antibody levels appeared to be directly related to the number of GP-Ag-positive hepatocytes. The variation trends for GP-Ag-positive hepatocytes were similar in the vaccine groups. In comparison with the control group, the optVP2 VLPs groups exhibited obviously better responses. These data indicate that the VLPs retained immunoreactivity and had strong immunogenicity in susceptible geese. Thus, GPV optVP2 appears to be a good candidate for the vaccination of goslings. Copyright © 2012 Elsevier B.V. All rights reserved.
Energy Technology Data Exchange (ETDEWEB)
Banerjee, Saikat; Shi, Heliang; Habte, Habtom H.; Qin, Yali; Cho, Michael W., E-mail: mcho@iastate.edu
2016-03-15
The C-terminal alpha-helix of gp41 membrane-proximal external region (MPER; {sup 671}NWFDITNWLWYIK{sup 683}) encompassing 4E10/10E8 epitopes is an attractive target for HIV-1 vaccine development. We previously reported that gp41-HR1-54Q, a trimeric protein comprised of the MPER in the context of a stable six-helix bundle (6HB), induced strong immune responses against the helix, but antibodies were directed primarily against the non-neutralizing face of the helix. To better target 4E10/10E8 epitopes, we generated four putative fusion intermediates by introducing double point mutations or deletions in the heptad repeat region 1 (HR1) that destabilize 6HB in varying degrees. One variant, HR1-∆10-54K, elicited antibodies in rabbits that targeted W672, I675 and L679, which are critical for 4E10/10E8 recognition. Overall, the results demonstrated that altering structural parameters of 6HB can influence immunogenic properties of the MPER and antibody targeting. Further exploration of this strategy could allow development of immunogens that could lead to induction of 4E10/10E8-like antibodies. - Highlights: • Four gp41 MPER-based immunogens that resemble fusion intermediates were generated. • C-terminal region of MPER that contains 4E10/10E8 epitopes was highly immunogenic. • Altering 6HB structure can influence immunogenic properties of the MPER. • Induced antibodies targeted multiple residues critical for 4E10/10E8 binding. • Development of immunogens based on fusion intermediates is a promising strategy.
Kobayashi, Maki; Aida, Masatoshi; Nagaoka, Hitoshi; Begum, Nasim A; Kitawaki, Yoko; Nakata, Mikiyo; Stanlie, Andre; Doi, Tomomitsu; Kato, Lucia; Okazaki, Il-mi; Shinkura, Reiko; Muramatsu, Masamichi; Kinoshita, Kazuo; Honjo, Tasuku
2009-12-29
To initiate class switch recombination (CSR) activation-induced cytidine deaminase (AID) induces staggered nick cleavage in the S region, which lies 5' to each Ig constant region gene and is rich in palindromic sequences. Topoisomerase 1 (Top1) controls the supercoiling of DNA by nicking, rotating, and religating one strand of DNA. Curiously, Top1 reduction or AID overexpression causes the genomic instability. Here, we report that the inactivation of Top1 by its specific inhibitor camptothecin drastically blocked both the S region cleavage and CSR, indicating that Top1 is responsible for the S region cleavage in CSR. Surprisingly, AID expression suppressed Top1 mRNA translation and reduced its protein level. In addition, the decrease in the Top1 protein by RNA-mediated knockdown augmented the AID-dependent S region cleavage, as well as CSR. Furthermore, Top1 reduction altered DNA structure of the Smu region. Taken together, AID-induced Top1 reduction alters S region DNA structure probably to non-B form, on which Top1 can introduce nicks but cannot religate, resulting in S region cleavage.
Chunghan Li; Chang-Shyh Peng; Daisy F. Sang
2013-01-01
Augmented Reality is an application which combines a live view of real-world environment and computer-generated images. This paper studies and demonstrates an efficient Augmented Reality development in the mobile Android environment with the native Java language and Android SDK. Major components include Barcode Reader, File Loader, Marker Detector, Transform Matrix Generator, and a cloud database.
Bioinformatics and multiepitope DNA immunization to design rational snake antivenom.
Directory of Open Access Journals (Sweden)
Simon C Wagstaff
2006-06-01
Full Text Available Snake venom is a potentially lethal and complex mixture of hundreds of functionally diverse proteins that are difficult to purify and hence difficult to characterize. These difficulties have inhibited the development of toxin-targeted therapy, and conventional antivenom is still generated from the sera of horses or sheep immunized with whole venom. Although life-saving, antivenoms contain an immunoglobulin pool of unknown antigen specificity and known redundancy, which necessitates the delivery of large volumes of heterologous immunoglobulin to the envenomed victim, thus increasing the risk of anaphylactoid and serum sickness adverse effects. Here we exploit recent molecular sequence analysis and DNA immunization tools to design more rational toxin-targeted antivenom.We developed a novel bioinformatic strategy that identified sequences encoding immunogenic and structurally significant epitopes from an expressed sequence tag database of a venom gland cDNA library of Echis ocellatus, the most medically important viper in Africa. Focusing upon snake venom metalloproteinases (SVMPs that are responsible for the severe and frequently lethal hemorrhage in envenomed victims, we identified seven epitopes that we predicted would be represented in all isomers of this multimeric toxin and that we engineered into a single synthetic multiepitope DNA immunogen (epitope string. We compared the specificity and toxin-neutralizing efficacy of antiserum raised against the string to antisera raised against a single SVMP toxin (or domains or antiserum raised by conventional (whole venom immunization protocols. The SVMP string antiserum, as predicted in silico, contained antibody specificities to numerous SVMPs in E. ocellatus venom and venoms of several other African vipers. More significantly, the antiserum cross-specifically neutralized hemorrhage induced by E. ocellatus and Cerastes cerastes cerastes venoms.These data provide valuable sequence and structure
Xing, Jing; Xu, Hongsen; Wang, Yang; Tang, Xiaoqian; Sheng, Xiuzhen; Zhan, Wenbin
2017-05-31
Vibrio anguillarum is a severe bacterial pathogen that can infect a wide range of fish species. Identification of immunogenic proteins and development of vaccine are essential for disease prevention. In this study, immunogenic proteins were screened and identified from V. anguillarum, and then protective efficacy of the immunogenic proteins was evaluated. Immunogenic proteins in V. anguillarum whole cell were detected by Western blotting (WB) using immunized flounder (Paralichthys olivaceus) serum, and then identified by Mass spectrometry (MS). The recombinant proteins of four identified immunogenic proteins were produced and immunized to fish, and then percentages of surface membrane immunoglobulin-positive (sIg+) cells in peripheral blood lymphocytes (PBL), total antibodies, antibodies against V. anguillarum, antibodies against recombinant proteins and relative percent survival (RPS) were measured, respectively. The results showed that five immunogenic proteins, VAA, Groel, OmpU, PteF and SpK, were identified; their recombinant proteins, rOmpU, rGroel, rSpK and rVAA, could induce the proliferation of sIg+ cells in PBL and production of total antibodies, antibodies against V. anguillarum and antibodies against the recombinant proteins; their protection against V. anguillarum showed 64.86%, 72.97%, 21.62% and 78.38% RPS, respectively. The results revealed that the immunoproteomic technique using fish anti-V. anguillarum serum provided an efficient way to screen the immunogenic protein for vaccine antigen. Moreover, the rVAA, rGroel and rOmpU had potential to be vaccine candidates against V. anguillarum infection. Copyright © 2017 Elsevier Ltd. All rights reserved.
Augmenting Locomotion in an Anthropomorphic System
Directory of Open Access Journals (Sweden)
Derek Wight
2005-02-01
Full Text Available A powered orthosis has applications ranging from assisting the elderly to augmenting astronauts. An assistive control scheme is developed that uses the force from a slave actuator to augment the force of a master actuator. This can be used to augment a closed-loop control scheme applied to the master actuator. Initially, actuator augmentation is explored both theoretically and experimentally using a simple mechanical system. The control scheme is then applied to a scale model of human lower limbs on a stationary bicycle to investigate the feasibility of a powered orthosis using pneumatic muscle actuators.
The role of imaging in pediatric bladder augmentation
Energy Technology Data Exchange (ETDEWEB)
Breen, Micheal; Chow, Jeanne S. [Boston Children' s Hospital, Department of Radiology, Boston, MA (United States); Phelps, Andrew [UCSF Benioff Children' s Hospital San Francisco, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); Estrada, Carlos [Boston Children' s Hospital, Department of Urology, Boston, MA (United States)
2015-09-15
Bladder augmentation (also called augmentation cystoplasty) refers to a number of surgical methods that increase the capacity and compliance of the urinary bladder. Imaging has an important role in the postoperative evaluation of bladder augmentation. The most common augmentation procedures utilize enteric segments to augment the bladder. The various types of bladder augmentation have characteristic appearances on different imaging modalities. Spontaneous bladder perforation is a complication that is seen in both early and late post-operative periods and it is one of the most important complications for radiologists to be aware of as it is life-threatening. We review the indications for bladder augmentation in children, the surgical techniques employed, the normal postoperative appearances on imaging studies and the role of imaging complications of bladder augmentation including delayed spontaneous bladder rupture, which is life-threatening. (orig.)
Directory of Open Access Journals (Sweden)
Liang CL
2015-03-01
Full Text Available Cheng-Loong Liang,1 Hao-Kwan Wang,1 Fei-Kai Syu,2 Kuo-Wei Wang,1 Kang Lu,1 Po-Chou Liliang1 1Department of Neurosurgery, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan; 2Department of Pharmacy, China Medical University Hospital, Taichung City, Taiwan Purpose: Postvertebral augmentation vertebral compression fractures are common; repeated vertebral augmentation is usually performed for prompt pain relief. This study aimed to evaluate the incidence and risk factors of repeat vertebral augmentation.Methods: We performed a retrospective, nationwide, population-based longitudinal observation study, using the National Health Insurance Research Database (NHIRD of Taiwan. All patients who received vertebral augmentation for vertebral compression fractures were evaluated. The collected data included patient characteristics (demographics, comorbidities, and medication exposure and repeat vertebral augmentation. Kaplan–Meier and stratified Cox proportional hazard regressions were performed for analyses.Results: The overall incidence of repeat vertebral augmentation was 11.3% during the follow-up until 2010. Patients with the following characteristics were at greater risk for repeat vertebral augmentation: female sex (AOR=1.24; 95% confidence interval [CI]: 1.10–2.36, advanced age (AOR=1.60; 95% CI: 1.32–2.08, diabetes mellitus (AOR=4.31; 95% CI: 4.05–5.88, cerebrovascular disease (AOR=4.09; 95% CI: 3.44–5.76, dementia (AOR=1.97; 95% CI: 1.69–2.33, blindness or low vision (AOR=3.72; 95% CI: 2.32–3.95, hypertension (AOR=2.58; 95% CI: 2.35–3.47, and hyperlipidemia (AOR=2.09; 95% CI: 1.67–2.22. Patients taking calcium/ vitamin D (AOR=2.98; 95% CI: 1.83–3.93, bisphosphonates (AOR=2.11; 95% CI: 1.26–2.61, or calcitonin (AOR=4.59; 95% CI: 3.40–5.77 were less likely to undergo repeat vertebral augmentation; however, those taking steroids (AOR=7.28; 95% CI: 6.32–8.08, acetaminophen (AOR=3.54; 95% CI: 2.75–4.83, or nonsteroidal
Hybrid-augmented intelligence:collaboration and cognition
Institute of Scientific and Technical Information of China (English)
Nan-ning ZHENG; Zi-yi LIU; Peng-ju REN; Yong-qiang MA; Shi-tao CHEN; Si-yu YU; Jian-ru XUE
2017-01-01
The long-term goal of artificial intelligence (AI) is to make machines learn and think like human beings. Due to the high levels of uncertainty and vulnerability in human life and the open-ended nature of problems that humans are facing, no matter how intelligent machines are, they are unable to completely replace humans. Therefore, it is necessary to introduce human cognitive capabilities or human-like cognitive models into AI systems to develop a new form of AI, that is, hybrid-augmented intelligence. This form of AI or machine intelligence is a feasible and important developing model. Hybrid-augmented intelligence can be divided into two basic models:one is human-in-the-loop augmented intelligence with human-computer collaboration, and the other is cognitive computing based augmented intelligence, in which a cognitive model is embedded in the machine learning system. This survey describes a basic framework for human-computer collaborative hybrid-augmented intelligence, and the basic elements of hybrid-augmented intelligence based on cognitive computing. These elements include intuitive reasoning, causal models, evolution of memory and knowledge, especially the role and basic principles of intuitive reasoning for complex problem solving, and the cognitive learning framework for visual scene understanding based on memory and reasoning. Several typical applications of hybrid-augmented intelligence in related fields are given.
ARSC: Augmented Reality Student Card--An Augmented Reality Solution for the Education Field
El Sayed, Neven A. M.; Zayed, Hala H.; Sharawy, Mohamed I.
2011-01-01
Augmented Reality (AR) is the technology of adding virtual objects to real scenes through enabling the addition of missing information in real life. As the lack of resources is a problem that can be solved through AR, this paper presents and explains the usage of AR technology we introduce Augmented Reality Student Card (ARSC) as an application of…
Mersiline mesh in premaxillary augmentation.
Foda, Hossam M T
2005-01-01
Premaxillary retrusion may distort the aesthetic appearance of the columella, lip, and nasal tip. This defect is characteristically seen in, but not limited to, patients with cleft lip nasal deformity. This study investigated 60 patients presenting with premaxillary deficiencies in which Mersiline mesh was used to augment the premaxilla. All the cases had surgery using the external rhinoplasty technique. Two methods of augmentation with Mersiline mesh were used: the Mersiline roll technique, for the cases with central symmetric deficiencies, and the Mersiline packing technique, for the cases with asymmetric deficiencies. Premaxillary augmentation with Mersiline mesh proved to be simple technically, easy to perform, and not associated with any complications. Periodic follow-up evaluation for a mean period of 32 months (range, 12-98 months) showed that an adequate degree of premaxillary augmentation was maintained with no clinically detectable resorption of the mesh implant.
Immunogenicity of Phleum pratense depigmented allergoid vaccines: experimental study in rabbits.
Iraola, V; Gallego, M T; López-Matas, M A; Morales, M; Bel, I; García, N; Carnés, J
2012-01-01
Immunogenicity studies are based on accurate preclinical and clinical assessment of pharmaceutical products. The immunogenicity of modified allergen vaccines has not been fully elucidated, and the mechanisms involved are not well understood. Animal and human models have recently shown that depigmented allergoids induce specific immunoglobulin (Ig) G against individual allergens, thus supporting the clinical efficacy of these vaccines. The aim of this study was to investigate the production of specific IgG against individual antigens and their isoforms in rabbits injected with depigmented allergoid extracts of Phleum pratense pollen. Two New Zealand rabbits were immunized with depigmented-polymerized extracts adsorbed onto aluminum hydroxide (Depigoid) of P pratense. Rabbits were injected 3 times (35 microg Phl p 5). Specific IgG titers against native, depigmented, and depigmented-polymerized extracts and individual allergens (rPhl p 1 and rPhl p 5a) were analyzed by direct enzyme-linked immunosorbent assay. The capacity of these synthesized antibodies to recognize individual native and depigmented allergens and different isoforms was evaluated by immunoblot and 2-D analysis. All rabbits produced high titers of specific IgG against the 3 extracts. Rabbits injected with depigmented allergoids produced similar specific antibody titers against native, depigmented, and depigmented-polymerized extracts. Serum samples recognized individual allergens and their isoforms in the nonmodified extracts. Vaccines containing depigmented allergoid extracts of P pratense induce immunogenicity in vivo. The antibodies produced after injection of these extracts clearly recognized allergens and different isoforms in their native configuration.
Augmented Reality-Guided Lumbar Facet Joint Injections.
Agten, Christoph A; Dennler, Cyrill; Rosskopf, Andrea B; Jaberg, Laurenz; Pfirrmann, Christian W A; Farshad, Mazda
2018-05-08
The aim of this study was to assess feasibility and accuracy of augmented reality-guided lumbar facet joint injections. A spine phantom completely embedded in hardened opaque agar with 3 ring markers was built. A 3-dimensional model of the phantom was uploaded to an augmented reality headset (Microsoft HoloLens). Two radiologists independently performed 20 augmented reality-guided and 20 computed tomography (CT)-guided facet joint injections each: for each augmented reality-guided injection, the hologram was manually aligned with the phantom container using the ring markers. The radiologists targeted the virtual facet joint and tried to place the needle tip in the holographic joint space. Computed tomography was performed after each needle placement to document final needle tip position. Time needed from grabbing the needle to final needle placement was measured for each simulated injection. An independent radiologist rated images of all needle placements in a randomized order blinded to modality (augmented reality vs CT) and performer as perfect, acceptable, incorrect, or unsafe. Accuracy and time to place needles were compared between augmented reality-guided and CT-guided facet joint injections. In total, 39/40 (97.5%) of augmented reality-guided needle placements were either perfect or acceptable compared with 40/40 (100%) CT-guided needle placements (P = 0.5). One augmented reality-guided injection missed the facet joint space by 2 mm. No unsafe needle placements occurred. Time to final needle placement was substantially faster with augmented reality guidance (mean 14 ± 6 seconds vs 39 ± 15 seconds, P Augmented reality-guided facet joint injections are feasible and accurate without potentially harmful needle placement in an experimental setting.
Cheung, King Sing
2014-01-01
Petri nets are a formal and theoretically rich model for the modelling and analysis of systems. A subclass of Petri nets, augmented marked graphs possess a structure that is especially desirable for the modelling and analysis of systems with concurrent processes and shared resources.This monograph consists of three parts: Part I provides the conceptual background for readers who have no prior knowledge on Petri nets; Part II elaborates the theory of augmented marked graphs; finally, Part III discusses the application to system integration. The book is suitable as a first self-contained volume
Directory of Open Access Journals (Sweden)
Viraj Kulkarni
Full Text Available HIV sequence diversity and potential decoy epitopes are hurdles in the development of an effective AIDS vaccine. A DNA vaccine candidate comprising of highly conserved p24(gag elements (CE induced robust immunity in all 10 vaccinated macaques, whereas full-length gag DNA vaccination elicited responses to these conserved elements in only 5 of 11 animals, targeting fewer CE per animal. Importantly, boosting CE-primed macaques with DNA expressing full-length p55(gag increased both magnitude of CE responses and breadth of Gag immunity, demonstrating alteration of the hierarchy of epitope recognition in the presence of pre-existing CE-specific responses. Inclusion of a conserved element immunogen provides a novel and effective strategy to broaden responses against highly diverse pathogens by avoiding decoy epitopes, while focusing responses to critical viral elements for which few escape pathways exist.
Product related factors influencing the immunogenicity of interferon beta-1b
Haji Abdolvahab, M.
2016-01-01
Therapeutic interferon beta is the first line treatment of relapsing remitting Multiple Sclerosis. However, despite their success in improving patient wellbeing, all IFNβ products encounter a significant problem: immunogenicity. In some patients, IFNβ products induce the formation of antidrug
Safety and immunogenicity of TetractHib (a vaccine combining DTP ...
African Journals Online (AJOL)
The safety and immunogenicity of TETRActHIB (a vaccine combining diphtheria and tetanus toxoids-pertussis vaccine (DTP) with Haemophilus influenzae type b (Hib) conjugate vaccine (polyribosyl ribitol phosphate conjugated to tetanus protein) (PRP-T)) was assessed in 131 Cape Town infants immunised at 6, 10 and 14 ...
DEFF Research Database (Denmark)
Antenucci, Fabio; Fougeroux, Cyrielle; Bosse, Janine T.
2017-01-01
and further characterized, both in silico and in vitro. Additionally, we analysed outer membrane vesicles (OMVs) of A. pleuropneumoniae MIDG2331 as potential immunogens, and compared deletions in degS and nlpI for increasing yields of OMVs compared to the parental strain. Our results indicated that Apf...
International Nuclear Information System (INIS)
Rubtsov, I.V.; Nedugova, G.I.; Samojlenko, I.I.
1984-01-01
The effect of ionizing radiation on immunogenic activity of crude cholera exotoxin (filtrate-toxin), which presents initial raw material to prepare native preventive treatment preparation cholergene-anatoxin has been studied. It is stated, that the use of gamma-radiation for the detoxification and sterilization of cholera exotoxin (crude), preserves its immunogenic properties. The observed increase in immunogenic activity, manifested in the reliable increase of antitoxic antibodies titre to the irradiation preparation over the whole period of observation, as compared with control, in the authors' assumption can be caused by the processes of polymerization and aggregation, taking place in protein molecule during irradiation, which results in the growth of molecule dimensions and in immunogenicity increase
International Nuclear Information System (INIS)
Lee, Miyoung; Jeong, Sang Young; Ha, Jueun; Kim, Miyeon; Jin, Hye Jin; Kwon, Soon-Jae; Chang, Jong Wook; Choi, Soo Jin; Oh, Wonil; Yang, Yoon Sun; Kim, Jae-Sung; Jeon, Hong Bae
2014-01-01
Highlights: • hUCB-MSCs maintained low immunogenicity even after immune challenge in vitro. • Humanized NSG mice were established using human UCB CD34+ cells. • Repeated intravenous hUCB-MSC injection into mice did not lead to immune responses and adverse events. • Allogeneic hUCB-MSCs maintained low immunogenicity in vitro and in vivo. - Abstract: Evaluation of the immunogenicity of human mesenchymal stem cells (MSCs) in an allogeneic setting during therapy has been hampered by lack of suitable models due to technical and ethical limitations. Here, we show that allogeneic human umbilical cord blood derived-MSCs (hUCB-MSCs) maintained low immunogenicity even after immune challenge in vitro. To confirm these properties in vivo, a humanized mouse model was established by injecting isolated hUCB-derived CD34+ cells intravenously into immunocompromised NOD/SCID IL2γnull (NSG) mice. After repeated intravenous injection of human peripheral blood mononuclear cells (hPBMCs) or MRC5 cells into these mice, immunological alterations including T cell proliferation and increased IFN-γ, TNF-α, and human IgG levels, were observed. In contrast, hUCB-MSC injection did not elicit these responses. While lymphocyte infiltration in the lung and small intestine and reduced survival rates were observed after hPBMC or MRC5 transplantation, no adverse events were observed following hUCB-MSC introduction. In conclusion, our data suggest that allogeneic hUCB-MSCs have low immunogenicity in vitro and in vivo, and are therefore “immunologically safe” for use in allogeneic clinical applications
Energy Technology Data Exchange (ETDEWEB)
Lee, Miyoung; Jeong, Sang Young; Ha, Jueun; Kim, Miyeon; Jin, Hye Jin; Kwon, Soon-Jae [Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874 (Korea, Republic of); Chang, Jong Wook [Research Institute for Future Medicine Stem Cell and Regenerative Medicine Center, Samsung Medical Center, Seoul 137-710 (Korea, Republic of); Choi, Soo Jin; Oh, Wonil; Yang, Yoon Sun [Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874 (Korea, Republic of); Kim, Jae-Sung [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-709 (Korea, Republic of); Jeon, Hong Bae, E-mail: jhb@medi-post.co.kr [Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874 (Korea, Republic of)
2014-04-18
Highlights: • hUCB-MSCs maintained low immunogenicity even after immune challenge in vitro. • Humanized NSG mice were established using human UCB CD34+ cells. • Repeated intravenous hUCB-MSC injection into mice did not lead to immune responses and adverse events. • Allogeneic hUCB-MSCs maintained low immunogenicity in vitro and in vivo. - Abstract: Evaluation of the immunogenicity of human mesenchymal stem cells (MSCs) in an allogeneic setting during therapy has been hampered by lack of suitable models due to technical and ethical limitations. Here, we show that allogeneic human umbilical cord blood derived-MSCs (hUCB-MSCs) maintained low immunogenicity even after immune challenge in vitro. To confirm these properties in vivo, a humanized mouse model was established by injecting isolated hUCB-derived CD34+ cells intravenously into immunocompromised NOD/SCID IL2γnull (NSG) mice. After repeated intravenous injection of human peripheral blood mononuclear cells (hPBMCs) or MRC5 cells into these mice, immunological alterations including T cell proliferation and increased IFN-γ, TNF-α, and human IgG levels, were observed. In contrast, hUCB-MSC injection did not elicit these responses. While lymphocyte infiltration in the lung and small intestine and reduced survival rates were observed after hPBMC or MRC5 transplantation, no adverse events were observed following hUCB-MSC introduction. In conclusion, our data suggest that allogeneic hUCB-MSCs have low immunogenicity in vitro and in vivo, and are therefore “immunologically safe” for use in allogeneic clinical applications.
[Cement augmentation on the spine : Biomechanical considerations].
Kolb, J P; Weiser, L; Kueny, R A; Huber, G; Rueger, J M; Lehmann, W
2015-09-01
Vertebral compression fractures are the most common osteoporotic fractures. Since the introduction of vertebroplasty and screw augmentation, the management of osteoporotic fractures has changed significantly. The biomechanical characteristics of the risk of adjacent fractures and novel treatment modalities for osteoporotic vertebral fractures, including pure cement augmentation by vertebroplasty, and cement augmentation of screws for posterior instrumentation, are explored. Eighteen human osteoporotic lumbar spines (L1-5) adjacent to vertebral bodies after vertebroplasty were tested in a servo-hydraulic machine. As augmentation compounds we used standard cement and a modified low-strength cement. Different anchoring pedicle screws were tested with and without cement augmentation in another cohort of human specimens with a simple pull-out test and a fatigue test that better reflects physiological conditions. Cement augmentation in the osteoporotic spine leads to greater biomechanical stability. However, change in vertebral stiffness resulted in alterations with the risk of adjacent fractures. By using a less firm cement compound, the risk of adjacent fractures is significantly reduced. Both screw augmentation techniques resulted in a significant increase in the withdrawal force compared with the group without cement. Augmentation using perforated screws showed the highest stability in the fatigue test. The augmentation of cement leads to a significant change in the biomechanical properties. Differences in the stability of adjacent vertebral bodies increase the risk of adjacent fractures, which could be mitigated by a modified cement compound with reduced strength. Screws that were specifically designed for cement application displayed greatest stability in the fatigue test.
Impairing DNA methylation obstructs memory enhancement for at least 24?hours in Lymnaea
Rothwell, Cailin M.; Lukowiak, Ken D.
2017-01-01
ABSTRACT Stressor-induced memory enhancement has previously been shown to involve DNA methylation in the mollusc Lymnaea stagnalis. Specifically, injection of the DNA methylation inhibitor 5-AZA one hour before exposure to a memory-enhancing stressor obstructs memory augmentation. However, the duration of the influence of 5-AZA on this memory enhancement has not yet been examined. In this study, 2 memory-enhancing stressors (a thermal stress and exposure to the scent of a predator) were used ...
DEFF Research Database (Denmark)
Møller, H J; Møller-Pedersen, T; Damsgaard, T E
1995-01-01
The prototype monoclonal keratan sulphate (KS) antibody 5D4 that is widely used for detection of KS in tissues and biological fluids reacts strongly with commercial low grade shark cartilage chondroitin 6-sulphate. Characterization of the immunogenic material by chondroitinase ABC digestion, ELISA...... cartilage chondroitin 6-sulphate is an easy accessible source of immunogenic KS that can be used as a reference standard and as coating antigen in KS-ELISAs. The concentration of immunogenic KS in synovial fluid measured with an ELISA based solely on reagents of shark cartilage chondroitin 6-sulphate...... correlated well (r = 0.90) with the concentrations obtained with a traditional KS-ELISA that uses purified aggrecan as standard and coating antigen, and KS in both serum and synovial fluid could be measured with sufficient linearity....
Tailoring DNA vaccines: designing strategies against HER2 positive cancers
Directory of Open Access Journals (Sweden)
Cristina eMarchini
2013-05-01
Full Text Available The crucial role of HER2 in epithelial transformation and its selective overexpression on cancer tissues makes it an ideal target for cancer immunotherapies such as passive immunotherapy with Trastuzumab. There are, however, a number of concerns regarding the use of monoclonal antibodies which include resistance, repeated treatments, considerable costs and side effects that make active immunotherapies against HER2 desirable alternative approaches. The efficacy of anti-HER2 DNA vaccination has been widely demonstrated in transgenic cancer-prone mice, which recapitulate several features of human breast cancers. Nonetheless, the rational design of a cancer vaccine able to trigger a long lasting immunity, and thus prevent tumor recurrence in patients, would require the understanding of how tolerance and immunosuppression regulate antitumor immune responses and, at the same time, the identification of the most immunogenic portions of the target protein. We herein retrace the findings that led to our most promising DNA vaccines that, by encoding human/rat chimeric forms of HER2, are able to circumvent peripheral tolerance. Preclinical data obtained with these chimeric DNA vaccines have provided the rationale for their use in an ongoing phase I clinical trial (EudraCT 2011-001104-34.
Screening and Identification of ssDNA Aptamer for Human GP73
Directory of Open Access Journals (Sweden)
Jingchun Du
2015-01-01
Full Text Available As one tumor marker of HCC, Golgi Protein 73 (GP73 is given more promise in the early diagnosis of HCC, and aptamers have been developed to compete with antibodies as biorecognition probes in different detection system. In this study, we utilized GP73 to screen specific ssDNA aptamers by SELEX technique. First, GP73 proteins were expressed and purified by prokaryotic expression system and Nickle ion affinity chromatography, respectively. At the same time, the immunogenicity of purified GP73 was confirmed by Western blotting. The enriched ssDNA library with high binding capacity for GP73 was obtained after ten rounds of SELEX. Then, thirty ssDNA aptamers were sequenced, in which two ssDNA aptamers with identical DNA sequence were confirmed, based on the alignment results, and designated as A10-2. Furthermore, the specific antibody could block the binding of A10-2 to GP73, and the specific binding of A10-2 to GP73 was also supported by the observation that several tumor cell lines exhibited variable expression level of GP73. Significantly, the identified aptamer A10-2 could distinguish normal and cancerous liver tissues. So, our results indicate that the aptamer A10-2 might be developed into one molecular probe to detect HCC from normal liver specimens.
International Nuclear Information System (INIS)
Ishihara, Hiroshi; Tanaka, Izumi; Yakumaru, Haruko
2010-01-01
Molecular mechanisms of intracellular response after DNA-damage by exposure to ionizing radiation have been studied. In the case of cells isolated from living body of human and experimental animals, alteration of the responsiveness by physiological oscillation such as circadian rhythm must be considered. To examine the circadian variation in the response of p53-responsible genes p21, mdm2, bax, and puma, we established a method to quantitate their mRNA levels with high reproducibility and accuracy based on real-time reverse transcription polymerase chain reaction (RT-PCR) and compared the levels of responsiveness in mouse hemocytes after diurnal irradiation to that after nocturnal irradiation. Augmentations of p21 and mdm2 mRNA levels with growth-arrest and of puma mRNA before apoptosis were confirmed by time-course experiment in RAW264.7, and dose-dependent increases in the peak levels of all the RNA were shown. Similarly, the relative RNA levels of p21, mdm2, bax, and puma per glyceraldehyde-3-phosphate dehydrogenase (GAPDH) also increased dose-dependently in peripheral blood and bone marrow cells isolated from whole-body-irradiated mice. Induction levels of all messages reduced by half after nighttime irradiation as compared with daytime irradiation in blood cells. In marrow cells, nighttime irradiation enhanced the p21 and mdm2 mRNA levels than daytime irradiation. No significant difference in bax or puma mRNA levels was observed between nighttime and daytime irradiation in marrow cells. This suggests that early-stage cellular responsiveness in DNA damage-induced genes is modulated between diurnal and nocturnal irradiation. (author)
... or bigger compared to the nose. The best candidates for chin augmentation are people with weak or ... www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. ...
Mullen, Tony
2011-01-01
Learn to create augmented reality apps using Processing open-source programming language Augmented reality (AR) is used all over, and you may not even realize it. Smartphones overlay data onto live camera views to show homes for sale, restaurants, or historical sites. American football broadcasts use AR to show the invisible first-down line on the field to TV viewers. Nike and Budweiser, among others, have used AR in ads. Now, you can learn to create AR prototypes using 3D data, Processing open-source programming language, and other languages. This unique book is an easy-to-follow guide on how
Augmented reality som wearable technology
DEFF Research Database (Denmark)
Rahn, Annette
“How Augmented reality can facilitate learning in visualizing human anatomy “ At this station I demonstrate how Augmented reality can be used to visualize the human lungs in situ and as a wearable technology which establish connection between body, image and technology in education. I will show...
International Nuclear Information System (INIS)
White, A.; Crosby, S.R.; Ratcliffe, W.A.; Smith, G.N.
1985-01-01
Testosterone 19-0-carboxymethyl ether (T19C) and 19-hemisuccinate (T19H) derivatives were synthesised and coupled to bovine serum albumin (BSA) or porcine thyroglobulin (PT) for immunogens or to iodohistamine for radioligands. The immunogenicity of these conjugates in mice was compared with those of testosterone 3-0-carboxymethyloxime and 15β-thioethyl conjugates. Of 10 immunogens studied, those linked to PT gave the highest antiserum titres and more sensitive standard curves. Cross-reactivity with 5α-dihydrotestosterone (DHT) was in the range 22-100%, for the 19-linked immunogens. Antisera to T19C and T19H conjugated to PT were then raised in rabbits and characterised with 4 radioligands. Homologous assay systems in which the chemical bridge was identical in immunogen and 125 I-radioligand gave the highest antiserum titres but the poorest assay sensitivity while those heterologous with respect to bridge or site gave the most sensitive standard curves. Rabbit antisera to both T19C and T19H immunogens showed good specificities with respect to DHT androstenedione (AN) and progesterone (PO) with all radioligands. The best assay system employed an antiserum to the T19H-PT immunogen with heterologous radioligand [ 125 I]T19C. It had a detection limit of 15pg/tube and low cross-reactivity with DHT and AN. (author)
International Nuclear Information System (INIS)
Bu Zhigao; Ye Ling; Compans, Richard W.; Yang Chinglai
2003-01-01
Codon-optimized genes were synthesized for the SIVmac239 Gag, a mutant Gag with mutations in the major homology region, and a chimeric Gag containing a protein destruction signal at the N-terminus of Gag. The mutant and chimeric Gag were expressed at levels comparable to that observed for the wild-type Gag protein but their stability and release into the medium were found to be significantly reduced. Immunization of mice with DNA vectors encoding the mutant or chimeric Gag induced fourfold higher levels of anti-SIV Gag CD4 T cell responses than the DNA vector encoding the wild-type SIV Gag. Moreover, anti-SIV Gag CD8 T cell responses induced by DNA vectors encoding the mutant or chimeric Gag were found to be 5- to 10-fold higher than those induced by the DNA construct for the wild-type Gag. These results indicate that mutations disrupting assembly and/or stability of the SIV Gag protein effectively enhance its immunogenicity when expressed from DNA vaccines
Genetic polymorphisms in prehistoric Pacific islanders determined by analysis of ancient bone DNA.
Hagelberg, E; Clegg, J B
1993-05-22
A previously characterized Asian-specific mitochondrial DNA (mtDNA) length mutation has been detected in DNA isolated from prehistoric human bones from Polynesia, including Hawaii, Chatham Islands and Society Islands. In contrast, the Asian mutation was absent in skeletal samples from the Melanesian archipelagos of New Britain and Vanuatu and in the oldest samples from Fiji, Tonga and Samoa in the central Pacific (2700-1600 years BP) although it was present in a more recent prehistoric sample from Tonga. These results, augmented by informative DNA sequence data from the hypervariable region of mtDNA, fail to support current views that the central Pacific was settled directly by voyagers from island Southeast Asia, the putative ancestors of modern Polynesians. An earlier occupation by peoples from the neighbouring Melanesian archipelagos seems more likely.
International Nuclear Information System (INIS)
Lee, Ju Woon; Byun, Myung Woo; Kim, Jae Hun; Seo, Ji Hyun
2006-01-01
The irradiated house dust mite allergen showed the conformational change with disappearance of major allergen and aggregation to higher molecular weights. The irradiated house dust mite allergens showed the change of epitope from results of the reduction of binding ability of house dust mite-allergic patients' serum (IgE) and polyclonal rabbit IgG against the irradiated allergens. In assessment of immunogenicity and allergenicity, irradiated house dust mite allergen showed the reduction of allergenicity with decrease of concentration for IL-4 and IL-5, the cytokine inducing allergy. For the assessment of the possibility as therapeutic immunogen of irradiated house dust mite allergen, allergic induced-mouse model were established. Irradiated allergen showed the maintainment of immunogenicity and the reduction of allergenicity from the result of maintain of IgG and reduction of IgE. Blue spots against irradiated allergen decreased raising with radiation dose in passive cutaneous anaphylaxis. The therapeutic effect was measured by reduction of house dust mite-specific IgE, IL-4 and IL-5. Induction of allergy after immunization of irradiated house dust mite allergen decreased by the reduction of house dust mite-specific IgE and IL-4 release. Therefore, house dust mite allergen modified by irradiation could be used as an effective immunogens for the prevention and treatment of allergy
Interactive Assembly Guide using Augmented Reality
DEFF Research Database (Denmark)
Andersen, Martin; Andersen, Rasmus Skovgaard; Larsen, Christian Lindequist
2009-01-01
This paper presents an Augmented Reality system for aiding a pump assembling process at Grundfos, one of the leading pump producers. Stable pose estimation of the pump is required in order to augment the graphics correctly. This is achieved by matching image edges with synthesized edges from CAD...... norm. A dynamic visualization of the augmented graphics provides the user with guidance. Usability tests show that the accuracy of the system is sufficient for assembling the pump....
Directory of Open Access Journals (Sweden)
Tuanyuan eShi
2016-05-01
Full Text Available Rabbit coccidiosis, caused by infection of Eimeria spp. is one of the most severe parasitic diseases in rabbits. E. intestinalis is one of the most immunogenic species in rabbit coccidia. Due to the lack of genomic information and unsuccessful in vitro cultivation, genetic manipulation of rabbit coccidia lagged behind other apicomplexan parasites. Using regulatory sequences from E. tenella, we obtained a transgenic line of E. intestinalis expressing yellow fluorescent protein (YFP. YFP was continuously expressed throughout the whole life cycle. Morphological features of E. intestinalis in the different developmental stages were dynamically observed with the transgenic line. Some important features in the endogenous development stages were observed. Trophozoites were found as early as 4 h post inoculation. Two-types of schizonts and merozoites were observed in first three of the four schizogonies. Beside jejunum and ileum, gametogony stage and oocysts were also found in the duodenum and vermiform appendix. In addition, the transgenic strain was highly immunogenic but less pathogenic than the wild type. Considering the high immunogenicity of E. intestinalis and amenability to transfection with foreign genes, transgenic E. intestinalis could be a promising oral eukaryotic vaccine vector.
Homhuan, A.; Prakongpan, S.; Poomvises, P.; Maas, H.A.; Krommelin, D.; Kersten, G.; Jiskoot, W.
2004-01-01
The purpose of this study was to prepare and characterize virosomes and ISCOMs containing envelope proteins of Newcastle disease virus (NDV) and to evaluate their immunogenicity in target animals (chickens). Virosomes were prepared by solubilization of virus with either Triton X-100 or octyl
DEFF Research Database (Denmark)
Møller, H J; Møller-Pedersen, T; Damsgaard, T E
1995-01-01
The prototype monoclonal keratan sulphate (KS) antibody 5D4 that is widely used for detection of KS in tissues and biological fluids reacts strongly with commercial low grade shark cartilage chondroitin 6-sulphate. Characterization of the immunogenic material by chondroitinase ABC digestion, ELISA...... inhibition studies, immunoblotting and HPLC analyses confirmed the presence of substantial amounts of KS, probably as a large proteoglycan (> 120 kDa). Commercial and heterogenic glycosaminoglycan preparations therefore must be used with great caution in immunological analyses. On the other hand the shark...... cartilage chondroitin 6-sulphate is an easy accessible source of immunogenic KS that can be used as a reference standard and as coating antigen in KS-ELISAs. The concentration of immunogenic KS in synovial fluid measured with an ELISA based solely on reagents of shark cartilage chondroitin 6-sulphate...
Platteel, Anouk C M; Marit de Groot, A; Andersen, Peter; Ovaa, Huib; Kloetzel, Peter M; Mishto, Michele; Sijts, Alice J A M
2016-01-01
Most vaccines are based on protective humoral responses while for intracellular pathogens CD8(+) T cells are regularly needed to provide protection. However, poor processing efficiency of antigens is often a limiting factor in CD8(+) T cell priming, hampering vaccine efficacy. The multistage cDNA
Augmented reality for breast imaging.
Rancati, Alberto; Angrigiani, Claudio; Nava, Maurizio B; Catanuto, Giuseppe; Rocco, Nicola; Ventrice, Fernando; Dorr, Julio
2018-02-21
Augmented reality (AR) enables the superimposition of virtual reality reconstructions onto clinical images of a real patient, in real time. This allows visualization of internal structures through overlying tissues, thereby providing a virtual transparency vision of surgical anatomy. AR has been applied to neurosurgery, which utilizes a relatively fixed space, frames, and bony references; the application of AR facilitates the relationship between virtual and real data. Augmented Breast imaging (ABI) is described. Breast MRI studies for breast implant patients with seroma were performed using a Siemens 3T system with a body coil and a four-channel bilateral phased-array breast coil as the transmitter and receiver, respectively. The contrast agent used was (CA) gadolinium (Gd) injection (0.1 mmol/kg at 2 ml/s) by a programmable power injector. Dicom formated images data from 10 MRI cases of breast implant seroma and 10 MRI cases with T1-2 N0 M0 breast cancer, were imported and transformed into Augmented reality images. Augmented breast imaging (ABI) demonstrated stereoscopic depth perception, focal point convergence, 3D cursor use, and joystick fly-through. Augmented breast imaging (ABI) to the breast can improve clinical outcomes, giving an enhanced view of the structures to work on. It should be further studied to determine its utility in clinical practice.
Chen, Yang; Guo, Wanzhu; Xu, Zhiwen; Yan, Qigui; Luo, Yan; Shi, Qian; Chen, Dishi; Zhu, Ling; Wang, Xiaoyu
2011-06-16
Porcine parvovirus (PPV) VP2 gene has been successfully expressed in many expression systems resulting in self-assembly of virus-like particles (VLPs) with similar morphology to the native capsid. Here, a pseudorabies virus (PRV) system was adopted to express the PPV VP2 gene. A recombinant PRV SA215/VP2 was obtained by homologous recombination between the vector PRV viral DNA and a transfer plasmid. Then recombinant virus was purified with plaque purification, and its identity confirmed by PCR amplification, Western blot and indirect immunofluorescence (IFA) analyses. Electronic microscopy of PRV SA215/VP2 confirmed self-assembly of both pseudorabies virus and VLPs from VP2 protein. Immunization of piglets with recombinant virus elicited PRV-specific and PPV-specific humoral immune responses and provided complete protection against a lethal dose of PRV challenges. Gilts immunized with recombinant viruses induced PPV-specific antibodies, and significantly reduced the mortality rate of (1 of 28) following virulent PPV challenge compared with the control (7 of 31). Furthermore, PPV virus DNA was not detected in the fetuses of recombinant virus immunized gilts. In this study, a recombinant PRV SA215/VP2 virus expressing PPV VP2 protein was constructed using PRV SA215 vector. The safety, immunogenicity, and protective efficacy of the recombinant virus were demonstrated in piglets and primiparous gilts. This recombinant PRV SA215/VP2 represents a suitable candidate for the development of a bivalent vaccine against both PRV and PPV infection.
Aspects of User Experience in Augmented Reality
DEFF Research Database (Denmark)
Madsen, Jacob Boesen
in human factors related to Augmented Reality. This is investigated partly as how Augmented Reality applications are used in unsupervised settings, and partly in specific evaluations related to user performance in supervised settings. The thesis starts by introducing Augmented Reality to the reader......, followed by a presentation of the technical areas related to the field, and different human factor areas. As a contribution to the research area, this thesis presents five separate, but sequential, papers within the area of Augmented Reality.......In Augmented Reality applications, the real environment is annotated or enhanced with computer-generated graphics. This is a topic that has been researched in the recent decades, but for many people this is a brand new and never heard of topic. The main focus of this thesis is investigations...
Directory of Open Access Journals (Sweden)
Pavel Borský
2017-06-01
Full Text Available Crude coal tar (CCT contains polycyclic aromatic hydrocarbons (PAHs. Benzo[a]pyrene (BaP is metabolized into a highly reactive metabolite benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE that is able to bind to DNA and creates BPDE-DNA adducts. Adducted DNA becomes immunogenic and induces immune response by production of antibodies against BPDE-DNA adducts (Ab-BPDE-DNA. Circulating Ab-BPDE-DNA was proposed as potential biomarker of genotoxic exposure to BaP (PAHs. Goeckerman therapy (GT of psoriasis uses dermal application of CCT ointment (PAHs. In presented study (children with psoriasis treated by GT; n = 19 the therapy significantly increased the level of Ab-BPDE-DNA (EI = 0.29/0.19–0.34 vs. 0.31/0.25–0.40; median/lower–upper quartile; p < 0.01. The results support the idea of Ab-BPDE-DNA level as a possible tentative indicator of exposure, effects and susceptibility of the organism to the exposure of BaP (PAHs.
Directory of Open Access Journals (Sweden)
Gavin Churchyard
Full Text Available The safety and immunogenicity of SAAVI DNA-C2 (4 mg IM, SAAVI MVA-C (2.9 x 109 pfu IM and Novartis V2-deleted subtype C gp140 (100 mcg with MF59 adjuvant in various vaccination regimens was evaluated in HIV-uninfected adults in South Africa.Participants at three South African sites were randomized (1:1:1:1 to one of four vaccine regimens: MVA prime, sequential gp140 protein boost (M/M/P/P; concurrent MVA/gp140 (MP/MP; DNA prime, sequential MVA boost (D/D/M/M; DNA prime, concurrent MVA/gp140 boost (D/D/MP/MP or placebo. Peak HIV specific humoral and cellular responses were measured.184 participants were enrolled: 52% were female, all were Black/African, median age was 23 years (range, 18-42 years and 79% completed all vaccinations. 159 participants reported at least one adverse event, 92.5% were mild or moderate. Five, unrelated, serious adverse events were reported. The M/M/P/P and D/D/MP/MP regimens induced the strongest peak neutralizing and binding antibody responses and the greatest CD4+ T-cell responses to Env. All peak neutralizing and binding antibody responses decayed with time. The MVA, but not DNA, prime contributed to the humoral and cellular immune responses. The D/D/M/M regimen was poorly immunogenic overall but did induce modest CD4+ T-cell responses to Gag and Pol. CD8+ T-cell responses to any antigen were low for all regimens.The SAAVI DNA-C2, SAAVI MVA-C and Novartis gp140 with MF59 adjuvant in various combinations were safe and induced neutralizing and binding antibodies and cellular immune responses. Sequential immunization with gp140 boosted immune responses primed by MVA or DNA. The best overall immune responses were seen with the M/M/P/P regimen.ClinicalTrials.gov NCT01418235.
The HART I augmented electric gun facility
International Nuclear Information System (INIS)
Fikse, D.A.; Ciesar, J.A.; Wehrli, H.A.; Rimersma, H.; Docherty, E.F.; Pipich, C.W.
1991-01-01
This paper reports on an augmented electric gun system that has been commissioned. This system, called HART I (Hypervelocity Augmented Railgun Test), is built around a double augmented rail arrangement with a 1.27-cm square bore. It is powered by the SUVAC II 5.6-MJ distributed capacitor power supply. This arrangement allows operation in a simple, series augmented, or transaugmented gun system configuration. The objective of this facility is to perform materials research augmentation studies, and armature development in the 10-km/s regime. Armature masses of 2 to 4 g will be accelerated in a 4-m long barrel. Baseline bore materials will begin with conventional G9/GlidCop systems and then move into pyrolytic boron nitride/refractory materials. Hybrids, plasma, and ablation stabilized armature systems are planned. The gun system is instrumented with plasma and rail B probes for inbore velocity measurements. In addition, breech and muzzle voltages, currents, and external velocities are measured. The HART I system is currently performing hypervelocity experiments to verify the augmentation models
The Effect of Irradiation on the Immunogenity of Brucella Abortus
International Nuclear Information System (INIS)
Arifin, M.; Tuasikal, Boky J.; Endhang Pudjiastuti; Ernawati Yulia
2004-01-01
An experiment was carried out to study the effect of irradiation on the immunogenity of B. abortus. The B. abortus were irradiated by Gamma Cells ( 60 Co). An experiment were divided into four groups. The first group (V1) was inoculated by irradiated B. abortus with the dose of 0.25 kGy. The second group (V2) was inoculated by irradiated B. abortus with the dose of 0.50 kGy. The third group (V3) was inoculated by irradiated B. abortus with the dose of 0.75 kGy. The fourth group (V4) was inoculated by Brucella vaccine 8.19. The observation respectively were included purely test, safety test, RBT serological test, diffusion test, development the colony of B. abortus in lien, and pathology anatomic inspection. The results obtained showed that 0.25 kGy was the expectantly dose of irradiation which could not only decreasing the infectivity of B. abortus but also has the ability to become a good immunogen for stimulating the immune response in the experiment animals. (author)
Immunogenicity to therapeutic proteins: impact on PK/PD and efficacy.
Chirmule, Narendra; Jawa, Vibha; Meibohm, Bernd
2012-06-01
The development of therapeutic proteins requires the understanding of the relationship between the dose, exposure, efficacy, and toxicity of these molecules. Several intrinsic and extrinsic factors contribute to the challenges for measuring therapeutic proteins in a precise and accurate manner. In addition, induction of an immune response to therapeutic protein results in additional complexities in the analysis of the pharmacokinetic profile, toxicity, safety, and efficacy of this class of molecules. Assessment of immunogenicity of therapeutic proteins is a required aspect of regulatory filings for a licensing application and for the safe and efficacious use of these compounds. A systematic strategy and well-defined criteria for measuring anti-drug antibodies (ADA) have been established, to a large extent, through coordinated efforts. These recommendations are based on risk assessment and include the determination of ADA content (concentration/titer), affinity, immunoglobulin isotype/subtype, and neutralization capacity. This manuscript reviews the requirements necessary for understanding the nature of an ADA response in order to discern the impact of immunogenicity on pharmacokinetics/pharmacodynamics and efficacy.
Influences of obesity on the immunogenicity of Hepatitis B vaccine.
Liu, Fang; Guo, Zhirong; Dong, Chen
2017-05-04
Hepatitis B vaccine is regarded as the most effective method for the prevention of hepatitis B virus (HBV) infection. However, several factors such as age, body mass index and immunocompetent state have been reported to be associated with reduced immunization responses. The present commentary was aimed to discuss the influences of obesity on the immunogenicity of hepatitis B vaccines. Available peer-reviewed literatures, practice guidelines, and statistics published on hepatitis B vaccine in obesity between 1973 and 2015. Obesity was significantly associated with non-response to hepatitis B vaccine immunization. The risk of nonresponsiveness of hepatitis B vaccine among obese people increased with BMI. Moreover, the obesity might lead to an increased risk of HBV vaccine-escape mutations. The mechanism responsible for decreased immunization responses in obesity included leptin-induced systemic and B cell intrinsic inflammation, impaired T cell responses and lymphocyte division and proliferation. Therefore, more studies should be performed to analyze the influences of obesity on the immunogenicity of hepatitis B vaccines to improve the immunoprotecive effect of hepatitis B vaccines in future.
Augmented “Ouch!”. : How to create intersubjective augmented objects into which we can bump
Liberati, Nicola
2015-01-01
The aim of this work is to provide the elements to design an intersubjective augmented reality in order to make the augmented objects part of our everyday world. This work will analyse intersubjectivity from a phenomenological point of view using the works by Husserl and Schutz. Thanks to these two
Xu, Yi-Gang; Guan, Xue-Ting; Liu, Zhong-Mei; Tian, Chang-Yong
2015-01-01
Classical swine fever, caused by classical swine fever virus (CSFV), is a highly contagious disease that results in enormous economic losses in pig industries. The E2 protein is one of the main structural proteins of CSFV and is capable of inducing CSFV-neutralizing antibodies and cytotoxic T lymphocyte (CTL) activities in vivo. Thymosin α-1 (Tα1), an immune-modifier peptide, plays a very important role in the cellular immune response. In this study, genetically engineered Lactobacillus plantarum bacteria expressing CSFV E2 protein alone (L. plantarum/pYG-E2) and in combination with Tα1 (L. plantarum/pYG-E2-Tα1) were developed, and the immunogenicity of each as an oral vaccine to induce protective immunity against CSFV in pigs was evaluated. The results showed that recombinant L. plantarum/pYG-E2 and L. plantarum/pYG-E2-Tα1 were both able to effectively induce protective immune responses in pigs against CSFV infection by eliciting immunoglobulin A (IgA)-based mucosal, immunoglobulin G (IgG)-based humoral, and CTL-based cellular immune responses via oral vaccination. Significant differences (P plantarum/pYG-E2-Tα1 and L. plantarum/pYG-E2, suggesting a better immunogenicity of L. plantarum/pYG-E2-Tα1 as a result of the Tα1 molecular adjuvant that can enhance immune responsiveness and augment specific lymphocyte functions. Our data suggest that the recombinant Lactobacillus microecological agent expressing CSFV E2 protein combined with Tα1 as an adjuvant provides a promising strategy for vaccine development against CSFV. PMID:25819954
African Journals Online (AJOL)
1974-04-13
Apr 13, 1974 ... Complications encountered after breast augmentation are dealt with in .... in Phisohex or other suitable preparation for a few days before surgery ... In all cases, the prosthesis causes a fibrous tissue capsule to form around it.
Highly parallel translation of DNA sequences into small molecules.
Directory of Open Access Journals (Sweden)
Rebecca M Weisinger
Full Text Available A large body of in vitro evolution work establishes the utility of biopolymer libraries comprising 10(10 to 10(15 distinct molecules for the discovery of nanomolar-affinity ligands to proteins. Small-molecule libraries of comparable complexity will likely provide nanomolar-affinity small-molecule ligands. Unlike biopolymers, small molecules can offer the advantages of cell permeability, low immunogenicity, metabolic stability, rapid diffusion and inexpensive mass production. It is thought that such desirable in vivo behavior is correlated with the physical properties of small molecules, specifically a limited number of hydrogen bond donors and acceptors, a defined range of hydrophobicity, and most importantly, molecular weights less than 500 Daltons. Creating a collection of 10(10 to 10(15 small molecules that meet these criteria requires the use of hundreds to thousands of diversity elements per step in a combinatorial synthesis of three to five steps. With this goal in mind, we have reported a set of mesofluidic devices that enable DNA-programmed combinatorial chemistry in a highly parallel 384-well plate format. Here, we demonstrate that these devices can translate DNA genes encoding 384 diversity elements per coding position into corresponding small-molecule gene products. This robust and efficient procedure yields small molecule-DNA conjugates suitable for in vitro evolution experiments.
Marketing and Augmented Reality
Zelený, Martin
2010-01-01
The main goal of this diploma thesis is to identify the usage of augmented reality in contemporary marketing practice and the expectations of marketers for the future use. This will be achieved by conducting a quantitative and qualitative research among existing creative and advertising companies. Secondary goal is introducing the concept of augmented reality from the theoretical point of view and also description of potential utilization based on known examples. The tools for the practical p...
Augmented reality and its practical application
ZÍTKOVÁ, Helena
2011-01-01
This thesis combines topic of augmented reality with tourism. For analyzing the state of the use of augmented reality was composed case studies. It was created product, which is called Guide to mobile phone.
Augmented Fotonovelas: A Visual Methodology for Community Engaged Research
Hidalgo, LeighAnna Grace
2014-01-01
Augmented Fotonovelas draw upon the aesthetic of traditional fotonovelas, but incorporate new technologies--such as video interviews, interactive mapping, smart phone technology, and Augmented Reality (AR). Augmented Fotonovelas also make the most of the classic form, utilizing photographs, text, and bubble captions. Through this methodology, new and old come together to produce Augmented Scholarship. I define Augmented Scholarship as knowledge production bridging the gap between communities ...
Increased immunogenicity and protective efficacy of influenza M2e fused to a tetramerizing protein.
Directory of Open Access Journals (Sweden)
Anne-Marie Carola Andersson
Full Text Available The ectodomain of the matrix 2 protein (M2e of influenza A virus represents an attractive target for developing a universal influenza A vaccine, with its sequence being highly conserved amongst human variants of this virus. With the aim of targeting conformational epitopes presumably shared by diverse influenza A viruses, a vaccine (M2e-NSP4 was constructed linking M2e (in its consensus sequence to the rotavirus fragment NSP4(98-135; due to its coiled-coil region this fragment is known to form tetramers in aqueous solution and in this manner we hoped to mimick the natural configuration of M2e as presented in membranes. M2e-NSP4 was then evaluated side-by-side with synthetic M2e peptide for its immunogenicity and protective efficacy in a murine influenza challenge model. Here we demonstrate that M2e fused to the tetramerizing protein induces an accelerated, augmented and more broadly reactive antibody response than does M2e peptide as measured in two different assays. Most importantly, vaccination with M2e-NSP4 caused a significant decrease in lung virus load early after challenge with influenza A virus and maintained its efficacy against a lethal challenge even at very low vaccine doses. Based on the results presented in this study M2e-NSP4 merits further investigation as a candidate for or as a component of a universal influenza A vaccine.
Augmenting the Web through Open Hypermedia
DEFF Research Database (Denmark)
Bouvin, N.O.
2003-01-01
Based on an overview of Web augmentation and detailing the three basic approaches to extend the hypermedia functionality of the Web, the author presents a general open hypermedia framework (the Arakne framework) to augment the Web. The aim is to provide users with the ability to link, annotate, a......, and otherwise structure Web pages, as they see fit. The paper further discusses the possibilities of the concept through the description of various experiments performed with an implementation of the framework, the Arakne Environment......Based on an overview of Web augmentation and detailing the three basic approaches to extend the hypermedia functionality of the Web, the author presents a general open hypermedia framework (the Arakne framework) to augment the Web. The aim is to provide users with the ability to link, annotate...
Muzzle shunt augmentation of conventional railguns
International Nuclear Information System (INIS)
Parker, J.V.
1991-01-01
This paper reports on augmentation which is a technique for reducing the armature current and hence the armature power dissipation in a plasma armature railgun. In spite of the advantages, no large augmented railguns have been built, primarily due to the mechanical and electrical complexity introduced by the extra conductors required. it is possible to achieve some of the benefits of augmentation in a conventional railgun by diverting a fraction φ of the input current through a shunt path at the muzzle of the railgun. In particular, the relation between force and armature current is the same as that obtained in an n-turn, series-connected augmented railgun with n = 1/(1 - φ). The price of this simplification is a reduction in electrical efficiency and some additional complexity in the external electrical system
Aplikasi Web Augmented Reality Villa
Directory of Open Access Journals (Sweden)
Gede Yudha Prema Pangestu
2017-07-01
Full Text Available Bali is one of the highly developed tourist destination in Indonesia. The arrival of tourists having holiday in Bali led to increase residential needs with complete amenities. The occupancy rate of hotel and villa in Bali is increase significantlly during the long vacation. The emergence of new villa and hotel occupancy raises the level of competition in business, so it needs a correct use good marketing communication strategy in marketing the product in order to attract the attention of consumers. Web Application Augmented Reality Villa can help visualize the residential villa in three-dimensional shapes that look more attractive and practical. The use of brochures as written information and the application of augmented reality technology on the Web Application Augmented Reality Villa aims to develop an application that can provide information about the villa to visitors. Web Application uses Augmented Reality Villa designed by FlarToolkit library. Based on the test results show the application can display 3-dimensional objects by scanning marker villa in a brochure which already contain marker.
International Nuclear Information System (INIS)
Sedlar, Ales; Dolinsek, Tanja; Markelc, Bostjan; Prosen, Lara; Kranjc, Simona; Bosnjak, Masa; Blagus, Tanja; Cemazar, Maja; Sersa, Gregor
2012-01-01
Electrochemotherapy provides good local tumor control but requires adjuvant treatment for increased local response and action on distant metastasis. In relation to this, intramuscular interleukin-12 (IL-12) gene electro-transfer, which provides systemic shedding of IL-12, was combined with local electrochemotherapy with cisplatin. Furthermore, the dependence on tumor immunogenicity and immunocompetence of the host on combined treatment response was evaluated. Sensitivity of SA-1 sarcoma and TS/A carcinoma cells to electrochemotherapy with cisplatin was tested in vitro. In vivo, intratumoral electrochemotherapy with cisplatin (day 1) was combined with a single (day 0) or multiple (days 0, 2, 4) intramuscular murine IL-12 (mIL-12) gene electrotransfer. The antitumor effectiveness of combined treatment was evaluated on immunogenic murine SA-1 sarcoma in A/J mice and moderately immunogenic murine TS/A carcinoma, in immunocompetent BALB/c and immunodeficient SCID mice. Electrochemotherapy in vitro resulted in a similar IC 50 values for both sarcoma and carcinoma cell lines. However, in vivo electrochemotherapy was more effective in the treatment of sarcoma, the more immunogenic of the tumors, resulting in a higher log cell kill, longer specific tumor growth delay, and also 17% tumor cures compared to carcinoma where no tumor cures were observed. Adjuvant intramuscular mIL-12 gene electrotransfer increased the log cell kill in both tumor models, potentiating the specific tumor growth delay by a factor of 1.8-2 and increasing tumor cure rate by approximately 20%. In sarcoma tumors, the potentiation of the response by intramuscular mIL-12 gene electrotransfer was dose-dependent and also resulted in a faster onset of tumor cures. Comparison of the carcinoma response to the combined treatment modality in immunocompetent and immunodeficient mice demonstrated that the immune system is needed both for increased cell kill and for attaining tumor cures. Based on the comparison of
Directory of Open Access Journals (Sweden)
Mohammad Javad Bagheripour
2017-01-01
Full Text Available Background and Objectives: Botulism syndrome is caused by serotypes A-G of neurotoxins of Clostridium genus. Neurotoxin binding domain is an appropriate vaccine candidate due to its immunogenic activity. In this study, the immunogenicity of chitosan-based botulinum neurotoxin E binding domain recombinant candidate vaccine was investigated via mucosal route of administration. Methods: In this experimental study, chitosan nanoparticles containing rBoNT/E protein were synthesized by ionic gelation method and were administered orally and intranasally to mice. After each administration, IgG antibody titer was measured by ELISA method. Finally, all groups were challenged with active botulinum neurotoxin type E. Data were analyzed using Duncan and repeated ANOVA tests. The significance level was considered as p0.05, even intranasal route reduced the immunogenicity.
International Nuclear Information System (INIS)
Beddows, Simon; Franti, Michael; Dey, Antu K.; Kirschner, Marc; Iyer, Sai Prasad N.; Fisch, Danielle C.; Ketas, Thomas; Yuste, Eloisa; Desrosiers, Ronald C.; Klasse, Per Johan; Maddon, Paul J.; Olson, William C.; Moore, John P.
2007-01-01
The human immunodeficiency virus type 1 (HIV-1) surface envelope glycoprotein (Env) complex, a homotrimer containing gp120 surface glycoprotein and gp41 transmembrane glycoprotein subunits, mediates the binding and fusion of the virus with susceptible target cells. The Env complex is the target for neutralizing antibodies (NAbs) and is the basis for vaccines intended to induce NAbs. Early generation vaccines based on monomeric gp120 subunits did not confer protection from infection; one alternative approach is therefore to make and evaluate soluble forms of the trimeric Env complex. We have directly compared the immunogenicity in rabbits of two forms of soluble trimeric Env and monomeric gp120 based on the sequence of HIV-1 JR-FL . Both protein-only and DNA-prime, protein-boost immunization formats were evaluated, DNA-priming having little or no influence on the outcome. One form of trimeric Env was made by disrupting the gp120-gp41 cleavage site by mutagenesis (gp140 UNC ), the other contains an intramolecular disulfide bond to stabilize the cleaved gp120 and gp41 moieties (SOSIP.R6 gp140). Among the three immunogens, SOSIP.R6 gp140 most frequently elicited neutralizing antibodies against the homologous, neutralization-resistant strain, HIV-1 JR-FL . All three proteins induced NAbs against more sensitive strains, but the breadth of activity against heterologous primary isolates was limited. When antibodies able to neutralize HIV-1 JR-FL were detected, antigen depletion studies showed they were not directed at the V3 region but were targeted at other, undefined gp120 and also non-gp120 epitopes
Gamma-irradiated scrub typhus immunogens: analysis for residual replicating rickettsiae
International Nuclear Information System (INIS)
Eisenberg, G.H. Jr.; Osterman, J.V.; Stephenson, E.H.
1980-01-01
Scrub thyphus immunogens that received inadequate gamma radiation contained residual, viable rickettsiae. The presence of these organisms in the host was masked by the rapid immune response elicited by the large number of inactivated rickettsiae. Transfer of homogenized spleen cells from immunized mice to normal syngeneic recipients provided a sensitive technique for the detection of these viable, replicating organisms
An update on safety and immunogenicity of vaccines containing emulsion-based adjuvants.
Fox, Christopher B; Haensler, Jean
2013-07-01
With the exception of alum, emulsion-based vaccine adjuvants have been administered to far more people than any other adjuvant, especially since the 2009 H1N1 influenza pandemic. The number of clinical safety and immunogenicity evaluations of vaccines containing emulsion adjuvants has correspondingly mushroomed. In this review, the authors introduce emulsion adjuvant composition and history before detailing the most recent findings from clinical and postmarketing data regarding the effects of emulsion adjuvants on vaccine immunogenicity and safety, with emphasis on the most widely distributed emulsion adjuvants, MF59® and AS03. The authors also present a summary of other emulsion adjuvants in clinical development and indicate promising avenues for future emulsion-based adjuvant development. Overall, emulsion adjuvants have demonstrated potent adjuvant activity across a number of disease indications along with acceptable safety profiles.
Augmented Reality Comes to Physics
Buesing, Mark; Cook, Michael
2013-01-01
Augmented reality (AR) is a technology used on computing devices where processor-generated graphics are rendered over real objects to enhance the sensory experience in real time. In other words, what you are really seeing is augmented by the computer. Many AR games already exist for systems such as Kinect and Nintendo 3DS and mobile apps, such as…
Liang, Ruijing; Liu, Lanlan; He, Huamei; Chen, Zhikuan; Han, Zhiqun; Luo, Zhenyu; Wu, Zhihao; Zheng, Mingbin; Ma, Yifan; Cai, Lintao
2018-09-01
Metastatic triple-negative breast cancer (mTNBC) is an aggressive disease among women worldwide, characterized by high mortality and poor prognosis despite systemic therapy with radiation and chemotherapies. Photodynamic therapy (PDT) is an important strategy to eliminate the primary tumor, however its therapeutic efficacy against metastases and recurrence is still limited. Here, we employed a template method to develop the core-shell gold nanocage@manganese dioxide (AuNC@MnO 2 , AM) nanoparticles as tumor microenvironment responsive oxygen producers and near-infrared (NIR)-triggered reactive oxygen species (ROS) generators for oxygen-boosted immunogenic PDT against mTNBC. In this platform, MnO 2 shell degrades in acidic tumor microenvironment pH/H 2 O 2 conditions and generates massive oxygen to boost PDT effect of AM nanoparticles under laser irradiation. Fluorescence (FL)/photoacoustic (PA)/magnetic resonance (MR) multimodal imaging confirms the effective accumulation of AM nanoparticles with sufficient oxygenation in tumor site to ameliorate local hypoxia. Moreover, the oxygen-boosted PDT effect of AM not only destroys primary tumor effectively but also elicits immunogenic cell death (ICD) with damage-associated molecular patterns (DAMPs) release, which subsequently induces DC maturation and effector cells activation, thereby robustly evoking systematic antitumor immune responses against mTNBC. Hence, this oxygen-boosted immunogenic PDT nanosystem offers a promising approach to ablate primary tumor and simultaneously prevent tumor metastases via immunogenic abscopal effects. Copyright © 2018 Elsevier Ltd. All rights reserved.
Immunogenicity of UV-inactivated measles virus
International Nuclear Information System (INIS)
Zahorska, R.; Mazur, N.; Korbecki, M.
1978-01-01
By means of the antigen extinction limit test it was shown that a triple dose vaccination of guinea pigs with UV-inactivated measles virus gave better results, than a single dose vaccination which was proved by the very low immunogenicity index. For both vaccination schemes (single and triple) the immune response was only sligthly influenced by a change of dose from 10 5 to 10 6 HadU 50 /ml or by the addition of aluminum adjuvant. In the antigen extinction limit test the antibody levels were determined by two methods (HIT and NT) the results of which were statistically equivalent. The UV-inactivated measles virus was also found to induce hemolysis-inhibiting antibodies. (orig.) [de
Li, Jun; Shi, Jian-Li; Wu, Xiao-Yan; Fu, Fang; Yu, Jiang; Yuan, Xiao-Yuan; Peng, Zhe; Cong, Xiao-Yan; Xu, Shao-Jian; Sun, Wen-Bo; Cheng, Kai-Hui; Du, Yi-Jun; Wu, Jia-Qiang; Wang, Jin-Bao; Huang, Bao-Hua
2015-06-01
Nowadays, adjuvant is still important for boosting immunity and improving resistance in animals. In order to boost the immunity of porcine circovirus type 2 (PCV2) DNA vaccine, CpG motifs were inserted. In this study, the dose-effect was studied, and the immunity of PCV2 DNA vaccines by recombinant open reading frame 2 (ORF2) gene and CpG motifs was evaluated. Three-week-old Changbai piglets were inoculated intramuscularly with 200 μg, 400 μg, and 800 μg DNA vaccines containing 14 and 18 CpG motifs, respectively. Average gain and rectum temperature were recorded everyday during the experiments. Blood was collected from the piglets after vaccination to detect the changes of specific antibodies, interleukin-2, and immune cells every week. Tissues were collected for histopathology and polymerase chain reaction. The results indicated that compared to those of the control piglets, all concentrations of two DNA vaccines could induce PCV2-specific antibodies. A cellular immunity test showed that PCV2-specific lymphocytes proliferated the number of TH, TC, and CD3+ positive T-cells raised in the blood of DNA vaccine immune groups. There was no distinct pathological damage and viremia occurring in pigs that were inoculated with DNA vaccines, but there was some minor pathological damage in the control group. The results demonstrated that CpG motifs as an adjuvant could boost the humoral and cellular immunity of pigs to PCV2, especially in terms of cellular immunity. Comparing two DNA vaccines that were constructed, the one containing 18 CpG motifs was more effective. This is the first report that CpG motifs as an adjuvant insert to the PCV2 DNA vaccine could boost immunity.
Neutralization escape mutants define a dominant immunogenic neutralization site on hepatitis A virus
International Nuclear Information System (INIS)
Stapleton, J.T.; Lemon, S.M.
1987-01-01
Hepatitis A virus is an hepatotrophic human picornavirus which demonstrates little antigenic variability. To topologically map immunogenic sites on hepatitis A virus which elicit neutralizing antibodies, eight neutralizing monoclonal antibodies were evaluated in competition immunoassays employing radiolabeled monoclonal antibodies and HM-175 virus. Whereas two antibodies (K3-4C8 and K3-2F2) bound to intimately overlapping epitopes, the epitope bound by a third antibody (B5-B3) was distinctly different as evidenced by a lack of competition between antibodies for binding to the virus. The other five antibodies variably blocked the binding of both K3-4C8-K3-2F2 and B5-B3, suggesting that these epitopes are closely spaced and perhaps part of a single neutralization immunogenic site. Several combinations of monoclonal antibodies blocked the binding of polyclonal human convalescent antibody by greater than 96%, indicating that the neutralization epitopes bound by these antibodies are immunodominant in humans. Spontaneously arising HM-175 mutants were selected for resistance to monoclonal antibody-mediated neutralization. Neutralization resistance was associated with reduced antibody binding. These results suggest that hepatitis A virus may differ from poliovirus in possessing a single, dominant neutralization immunogenic site and therefore may be a better candidate for synthetic peptide or antiidiotype vaccine development
Augmented reality implementation methods in mainstream applications
Directory of Open Access Journals (Sweden)
David Procházka
2011-01-01
Full Text Available Augmented reality has became an useful tool in many areas from space exploration to military applications. Although used theoretical principles are well known for almost a decade, the augmented reality is almost exclusively used in high budget solutions with a special hardware. However, in last few years we could see rising popularity of many projects focused on deployment of the augmented reality on different mobile devices. Our article is aimed on developers who consider development of an augmented reality application for the mainstream market. Such developers will be forced to keep the application price, therefore also the development price, at reasonable level. Usage of existing image processing software library could bring a significant cut-down of the development costs. In the theoretical part of the article is presented an overview of the augmented reality application structure. Further, an approach for selection appropriate library as well as the review of the existing software libraries focused in this area is described. The last part of the article outlines our implementation of key parts of the augmented reality application using the OpenCV library.
Directory of Open Access Journals (Sweden)
Shailbala Singh
2014-10-01
Full Text Available Gene-based vaccination strategies, specifically viral vectors encoding vaccine immunogens are effective at priming strong immune responses. Mucosal routes offer practical advantages for vaccination by ease of needle-free administration, and immunogen delivery at readily accessible oral/nasal sites to efficiently induce immunity at distant gut and genital tissues. However, since mucosal tissues are inherently tolerant for induction of immune responses, incorporation of adjuvants for optimal mucosal vaccination strategies is important. We report here the effectiveness of alpha-galactosylceramide (α-GalCer, a synthetic glycolipid agonist of natural killer T (NKT cells, as an adjuvant for enhancing immunogenicity of vaccine antigens delivered using viral vectors by mucosal routes in murine and nonhuman primate models. Significant improvement in adaptive immune responses in systemic and mucosal tissues was observed by including α-GalCer adjuvant for intranasal immunization of mice with vesicular stomatitis virus vector encoding the model antigen ovalbumin and adenoviral vectors expressing HIV env and Gag antigens. Activation of NKT cells in systemic and mucosal tissues along with significant increases in adaptive immune responses were observed in rhesus macaques immunized by intranasal and sublingual routes with protein or adenovirus vectored antigens when combined with α-GalCer adjuvant. These results support the utility of α-GalCer adjuvant for enhancing immunogenicity of mucosal vaccines delivered using viral vectors.
Energy Technology Data Exchange (ETDEWEB)
Lee, Ju Woon; Byun, Myung Woo; Kim, Jae Hun; Seo, Ji Hyun
2006-01-15
The irradiated house dust mite allergen showed the conformational change with disappearance of major allergen and aggregation to higher molecular weights. The irradiated house dust mite allergens showed the change of epitope from results of the reduction of binding ability of house dust mite-allergic patients' serum (IgE) and polyclonal rabbit IgG against the irradiated allergens. In assessment of immunogenicity and allergenicity, irradiated house dust mite allergen showed the reduction of allergenicity with decrease of concentration for IL-4 and IL-5, the cytokine inducing allergy. For the assessment of the possibility as therapeutic immunogen of irradiated house dust mite allergen, allergic induced-mouse model were established. Irradiated allergen showed the maintainment of immunogenicity and the reduction of allergenicity from the result of maintain of IgG and reduction of IgE. Blue spots against irradiated allergen decreased raising with radiation dose in passive cutaneous anaphylaxis. The therapeutic effect was measured by reduction of house dust mite-specific IgE, IL-4 and IL-5. Induction of allergy after immunization of irradiated house dust mite allergen decreased by the reduction of house dust mite-specific IgE and IL-4 release. Therefore, house dust mite allergen modified by irradiation could be used as an effective immunogens for the prevention and treatment of allergy.
Evaluation of cellular responses for a chimeric HBsAg-HCV core DNA vaccine in BALB/c mice
Directory of Open Access Journals (Sweden)
Maryam Yazdanian
2015-01-01
Conclusion: Fusion of HBsAg to HCVcp in the context of a DNA vaccine modality could augment Th1-oriented cellular and CTL responses toward a protective epitope, comparable to that of HCVcp (subunit HCV vaccine immunization.
Directory of Open Access Journals (Sweden)
Barney S Graham
Full Text Available DNA vaccine immunogenicity has been limited by inefficient delivery. Needle-free delivery of DNA using a CO2-powered Biojector® device was compared to delivery by needle and syringe and evaluated for safety and immunogenicity.Forty adults, 18-50 years, were randomly assigned to intramuscular (IM vaccinations with DNA vaccine, VRC-HIVDNA016-00-VP, (weeks 0, 4, 8 by Biojector® 2000™ or needle and syringe (N/S and boosted IM at week 24 with VRC-HIVADV014-00-VP (rAd5 with N/S at 10(10 or 10(11 particle units (PU. Equal numbers per assigned schedule had low (≤500 or high (>500 reciprocal titers of preexisting Ad5 neutralizing antibody.120 DNA and 39 rAd5 injections were given; 36 subjects completed follow-up research sample collections. IFN-γ ELISpot response rates were 17/19 (89% for Biojector® and 13/17 (76% for N/S delivery at Week 28 (4 weeks post rAd5 boost. The magnitude of ELISpot response was about 3-fold higher in Biojector® compared to N/S groups. Similar effects on response rates and magnitude were observed for CD8+, but not CD4+ T-cell responses by ICS. Env-specific antibody responses were about 10-fold higher in Biojector-primed subjects.DNA vaccination by Biojector® was well-tolerated and compared to needle injection, primed for greater IFN-γ ELISpot, CD8+ T-cell, and antibody responses after rAd5 boosting.ClinicalTrials.gov NCT00109629.
Augmented reality som wearable
DEFF Research Database (Denmark)
Buhl, Mie; Rahn, Annette
2015-01-01
Artiklen omhandler design og implementering af Augmented Reality (AR) i form af en wearable i sygeplejerskeuddannelsens anatomiundervisning, mere specifikt undervisning i lungeanatomi og respiration, med fokus på potentialer for visuel læring. Projektet undersøger, hvordan en udviklet AR-applikat......Artiklen omhandler design og implementering af Augmented Reality (AR) i form af en wearable i sygeplejerskeuddannelsens anatomiundervisning, mere specifikt undervisning i lungeanatomi og respiration, med fokus på potentialer for visuel læring. Projektet undersøger, hvordan en udviklet AR...
Size, Shape, and Sequence-Dependent Immunogenicity of RNA Nanoparticles
Directory of Open Access Journals (Sweden)
Sijin Guo
2017-12-01
Full Text Available RNA molecules have emerged as promising therapeutics. Like all other drugs, the safety profile and immune response are important criteria for drug evaluation. However, the literature on RNA immunogenicity has been controversial. Here, we used the approach of RNA nanotechnology to demonstrate that the immune response of RNA nanoparticles is size, shape, and sequence dependent. RNA triangle, square, pentagon, and tetrahedron with same shape but different sizes, or same size but different shapes were used as models to investigate the immune response. The levels of pro-inflammatory cytokines induced by these RNA nanoarchitectures were assessed in macrophage-like cells and animals. It was found that RNA polygons without extension at the vertexes were immune inert. However, when single-stranded RNA with a specific sequence was extended from the vertexes of RNA polygons, strong immune responses were detected. These immunostimulations are sequence specific, because some other extended sequences induced little or no immune response. Additionally, larger-size RNA square induced stronger cytokine secretion. 3D RNA tetrahedron showed stronger immunostimulation than planar RNA triangle. These results suggest that the immunogenicity of RNA nanoparticles is tunable to produce either a minimal immune response that can serve as safe therapeutic vectors, or a strong immune response for cancer immunotherapy or vaccine adjuvants.
Passey, Chaitali; Suryawanshi, Satyendra; Sanghavi, Kinjal; Gupta, Manish
2018-02-26
The rapidly increasing number of therapeutic biologics in development has led to a growing recognition of the need for improvements in immunogenicity assessment. Published data are often inadequate to assess the impact of an antidrug antibody (ADA) on pharmacokinetics, safety, and efficacy, and enable a fully informed decision about patient management in the event of ADA development. The recent introduction of detailed regulatory guidance for industry should help address many past inadequacies in immunogenicity assessment. Nonetheless, careful analysis of gathered data and clear reporting of results are critical to a full understanding of the clinical relevance of ADAs, but have not been widely considered in published literature to date. Here, we review visualization and modeling of immunogenicity data. We present several relatively simple visualization techniques that can provide preliminary information about the kinetics and magnitude of ADA responses, and their impact on pharmacokinetics and clinical endpoints for a given therapeutic protein. We focus on individual sample- and patient-level data, which can be used to build a picture of any trends, thereby guiding analysis of the overall study population. We also discuss methods for modeling ADA data to investigate the impact of immunogenicity on pharmacokinetics, efficacy, and safety.
AUGMENTED REALITY - STATE OF KNOWLEDGE, USE AND EXPERIMENTATION
Directory of Open Access Journals (Sweden)
Mihaela Filofteia TUTUNEA
2013-12-01
Full Text Available Technologies for augmenting reality have been consolidated during the last decades, extending their applicability to more and more socio-economic areas. The rapid evolution of mobile technologies and virtualization of the digital environment have created auspicious conditions for massive extension and implementation of solutions for augmenting reality at global level. Experience has already shown that augmented reality, alongside virtual reality can offer very important support solutions in modeling the real world with the aim of extending the human capabilities of perception, allowing the opening of a new phase in the world’s socio-economic development. Starting from the evident tendencies that have manifested at global level in the development and implementation of augmented reality technologies, the paper begins with the presentation of the most important aspects related to augmented reality technologies, highlighting their main areas of application, and presents the study realized for identifying the level of knowledge, use and effective experimentation of augmented reality applications by mobile device users. The results of this study could be very useful to the socio-economic environment, starting with the field of research, continuing with developers and providers of augmented reality solutions, manufacturers and providers of hardware infrastructure support for augmented reality solutions and systems, final users of these solutions, both individuals and businesses, and experimenting digital communities.
International Nuclear Information System (INIS)
Yin Jiangmei; Dai Anlan; Laddy, Dominick J.; Yan Jian; Arango, Tatiana; Khan, Amir S.; Lewis, Mark G.; Andersen, Hanne; Kutzler, Michele A.; Draghia-Akli, Ruxandra; Weiner, David B.; Boyer, Jean D.
2009-01-01
Interleukin (IL)-15, is a cytokine that is important for the maintenance of long-lasting, high-avidity T cell response to invading pathogens and has, therefore, been used in vaccine and therapeutic platforms as an adjuvant. In addition to pure protein delivery, plasmids encoding the IL-15 gene have been utilized. However, it is critical to determine the appropriate dose to maximize the adjuvanting effects. We immunized rhesus macaques with different doses of IL-15 expressing plasmid in an influenza non-human primate immunogenicity model. We found that co-immunization of rhesus macaques with a Flu DNA-based vaccine and low doses of plasmid encoding macaque IL-15 enhanced the production of IFN-γ (0.5 mg) and the proliferation of CD4 + and CD8 + T cells, as well as T CM levels in proliferating CD8 + T cells (0.25 mg). Whereas, high doses of IL-15 (4 mg) decrease the production of IFN-γ and the proliferation of CD4 + and CD8 + T cells and T CM levels in the proliferating CD4 + and CD8 + T cells. In addition, the data of hemagglutination inhibition (HI) antibody titer suggest that although not significantly different, there appears to be a slight increase in antibodies at lower doses of IL-15. Importantly, however, the higher doses of IL-15 decrease the antibody levels significantly. This study demonstrates the importance of optimizing DNA-based cytokine adjuvants.
Chen, Yuhuang; Duan, Ran; Li, Xu; Li, Kewei; Liang, Junrong; Liu, Chang; Qiu, Haiyan; Xiao, Yuchun; Jing, Huaiqi; Wang, Xin
2015-12-01
The outer membrane protein A (OmpA) is one of the intra-species conserved proteins with immunogenicity widely found in the family of Enterobacteriaceae. Here we first confirmed OmpA is conserved in the three pathogenic Yersinia: Yersinia pestis, Yersinia pseudotuberculosis and pathogenic Yersinia enterocolitica, with high homology at the nucleotide level and at the amino acid sequence level. The identity of ompA sequences for 262 Y. pestis strains, 134 Y. pseudotuberculosis strains and 219 pathogenic Y. enterocolitica strains are 100%, 98.8% and 97.7% similar. The main pattern of OmpA of pathogenic Yersinia are 86.2% and 88.8% identical at the nucleotide and amino acid sequence levels, respectively. Immunological analysis showed the immunogenicity of each OmpA and cross-immunogenicity of OmpA for pathogenic Yersinia where OmpA may be a vaccine candidate for Y. pestis and other pathogenic Yersinia. Copyright © 2015 Elsevier Ltd. All rights reserved.
Empirical evaluation of augmented prototyping effectiveness
Directory of Open Access Journals (Sweden)
Tomáš Koubek
2012-01-01
Full Text Available Augmented reality is a scientific field well known for more than twenty years. Although there is a huge number of projects that present promising results, the real usage of augmented reality applications for fulfilling common tasks is almost negligible. We believe that one of the principal reasons is insufficient usability of these applications. The situation is analogous to the desktop, mobile or cloud application development or even to the web pages design. The first phase of a technology adoption is the exploration of its potential. As soon as the technical problems are overcome and the technology is widely accepted, the usability is a principal issue. The usability is utmost important also from the business point of view. The cost of augmented reality implementation into the production process is substantial, therefore, the usability that is directly responsible for the implemented solution effectiveness must be appropriately tested. Consequently, the benefit of the implemented solution can be measured.This article briefly outlines common techniques used for usability evaluation. Discussed techniques were designed especially for evaluation of desktop applications, mobile solutions and web pages. In spite of this drawback, their application on augmented reality products is usually possible. Further, a review of existing augmented reality project evaluations is presented.Based on this review, a usability evaluation method for our augmented prototyping application is proposed. This method must overcome the fact that the design is a creative process. Therefore, it is not possible to take into account common criteria such as time consumption.
Augmented reality in dentistry: a current perspective.
Kwon, Ho-Beom; Park, Young-Seok; Han, Jung-Suk
2018-02-21
Augmentation reality technology offers virtual information in addition to that of the real environment and thus opens new possibilities in various fields. The medical applications of augmentation reality are generally concentrated on surgery types, including neurosurgery, laparoscopic surgery and plastic surgery. Augmentation reality technology is also widely used in medical education and training. In dentistry, oral and maxillofacial surgery is the primary area of use, where dental implant placement and orthognathic surgery are the most frequent applications. Recent technological advancements are enabling new applications of restorative dentistry, orthodontics and endodontics. This review briefly summarizes the history, definitions, features, and components of augmented reality technology and discusses its applications and future perspectives in dentistry.
DEFF Research Database (Denmark)
Nielsen, Birgitte Lund; Brandt, Harald; Radmer, Ole
2017-01-01
Artiklen præsenterer resultater fra pilotafprøvning i 7.-klasses fysik/kemi og biologi af to Augmented Reality (AR)-apps til naturfagsundervisning. Muligheder og udfordringer ved lærerens stilladsering af elevernes undersøgende samtale og modelleringskompetence er undersøgt med interview...
Augmented Reality Tower Technology Assessment
Reisman, Ronald J.; Brown, David M.
2009-01-01
Augmented Reality technology may help improve Air Traffic Control Tower efficiency and safety during low-visibility conditions. This paper presents the assessments of five off-duty controllers who shadow-controlled' with an augmented reality prototype in their own facility. Initial studies indicated unanimous agreement that this technology is potentially beneficial, though the prototype used in the study was not adequate for operational use. Some controllers agreed that augmented reality technology improved situational awareness, had potential to benefit clearance, control, and coordination tasks and duties and could be very useful for acquiring aircraft and weather information, particularly aircraft location, heading, and identification. The strongest objections to the prototype used in this study were directed at aircraft registration errors, unacceptable optical transparency, insufficient display performance in sunlight, inadequate representation of the static environment and insufficient symbology.
Therapeutic options for lip augmentation.
Segall, Lorne; Ellis, David A F
2007-11-01
Aesthetic ideals vary with emerging fashion trends and within different cultures. However, over the past few decades, fuller lips have been considered a desirable trait. Many younger patients are presenting for lip augmentation to achieve the sought-after look commonly seen in many fashion magazines. In addition, as individuals age, they lose lip volume, with a thinning of the red lip, some effacement of the vermillion border, and elongation and flattening of the white portion of the lip. Rejuvenation of the lips plays a key role in restoring a more youthful appearance. As a result, lip augmentation appeals to a wide spectrum of patients who present with various different aesthetic goals and expectations. Numerous therapeutic options exist for aesthetic lip augmentation, ranging from temporary and permanent injectable fillers to implants and other surgical techniques.
Augmented Reality Interfaces for Additive Manufacturing
DEFF Research Database (Denmark)
Eiríksson, Eyþór Rúnar; Pedersen, David Bue; Frisvad, Jeppe Revall
2017-01-01
This paper explores potential use cases for using augmented reality (AR) as a tool to operate industrial machines. As a baseline we use an additive manufacturing system, more commonly known as a 3D printer. We implement novel augmented interfaces and controls using readily available open source...
Affordances in Mobile Augmented Reality Applications
Directory of Open Access Journals (Sweden)
Tor Gjøsæter
2014-10-01
Full Text Available This paper explores the affordances of augmented reality content in a mobile augmented reality application. A user study was conducted by performing a multi-camera video recording of seven think aloud sessions. The think aloud sessions consisted of individual users performing tasks, exploring and experiencing a mobile augmented reality (MAR application we developed for the iOS platform named ARad. We discuss the instrumental affordances we observed when users interacted with augmented reality content, as well as more complex affordances rising from conventions from media content, AR and the traditional WIMP paradigm. We find that remediation of traditional newspaper content through the MAR medium can provide engaging, pleasing and exciting user experiences. However, the some of the content still suffers from being shoveled onto the MAR platform without adapting it properly. Finally, we discuss what content was most successfully mediated to the user and how the content impacts the user experience.
Directory of Open Access Journals (Sweden)
Emanuele Montomoli
2018-03-01
Full Text Available Since the mid-1980s, two lineages of influenza B viruses have been distinguished. These can co-circulate, limiting the protection provided by inactivated trivalent influenza vaccines (TIVs. This has prompted efforts to formulate quadrivalent influenza vaccines (QIVs, to enhance protection against circulating influenza B viruses. This review describes the results obtained from seven phase III clinical trials evaluating the immunogenicity, safety, and lot-to-lot consistency of a new quadrivalent split-virion influenza vaccine (Vaxigrip Tetra® formulated by adding a second B strain to the already licensed TIV. Since Vaxigrip Tetra was developed by means of a manufacturing process strictly related to that used for TIV, the data on the safety profile of TIV are considered supportive of that of Vaxigrip Tetra. The safety and immunogenicity of Vaxigrip Tetra were similar to those of the corresponding licensed TIV. Moreover, the new vaccine elicits a superior immune response towards the additional strain, without affecting immunogenicity towards the other three strains. Vaxigrip Tetra is well tolerated, has aroused no safety concerns, and is recommended for the active immunization of individuals aged ≥6 months. In addition, preliminary data confirm its immunogenicity and safety even in children aged 6–35 months and its immunogenicity in older subjects (aged 66–80 years.
Lalsiamthara, Jonathan; Lee, John Hwa
2017-06-01
Intracellular pathogen Salmonella exhibits natural infection broadly analogous to Brucella, this phenomenon makes Salmonella a pragmatic choice for an anti-Brucella vaccine delivery platform. In this study we developed and formulated a combination of four attenuated Salmonella Typhimurium live vector strains delivering heterologous Brucella antigens (rBs), namely lumazine synthase, proline racemase subunit A, lipoprotein outer membrane protein-19, and Cu-Zn superoxide dismutase. With an aim to develop a cross-protecting vaccine, Brucella pan-species conserved rBs were selected. The present study compared the efficacy of smooth and rough variants of Salmonella delivery vector and also evaluated the inclusion of purified Brucella lipopolysaccharide (LPS) in the formulation. Immunization of SPF-BALB/c mice with the vaccine combinations significantly (P≤0.05) reduced splenic wild-type Brucella abortus 544 colonization as compared to non-immunized mice as well as Salmonella only immunized mice. Increased induction of Brucella specific-IgG, sIgA production, and antigen-specific splenocyte proliferative responses were observed in the mice immunized with the formulations as compared to naïve or vector only immunized mice. Modulatory effects of rB and LPS on production of interleukin (IL)-4, IL-12, and interferon-γ were detected in splenocytes of mice immunized with the formulation. Rough Salmonella variant in combination with LPS could further enhance the efficacy of the delivery when applied intraperitoneally. Taken together, it is compelling that Brucella LPS-augmented Salmonella vector delivering immunogenic Brucella proteins may be more suitable than the current non-ideal live Brucella abortus vaccine. The vaccine system also provides a basis for the development of cross-protecting vaccine capable of preventing multispecies brucellosis. Copyright © 2017 Elsevier B.V. All rights reserved.
Developing novel immunogens for a safe and effective Alzheimer's disease vaccine.
Lemere, Cynthia A
2009-01-01
, a safe and effective active Abeta vaccine would be more cost-effective and more readily available to a larger AD population. We have developed several novel short Abeta immunogens that target the Abeta N-terminus containing a strong B cell epitope while avoiding the Abeta mid-region and C-terminus containing T cell epitopes. These immunogens include dendrimeric Abeta1-15 (16 copies of Abeta1-15 on a lysine antigen tree), 2xAbeta1-15 (a tandem repeat of two lysine-linked Abeta1-15 peptides), and 2xAbeta1-15 with the addition of a three amino acid RGD motif (R-2xAbeta1-15). Intranasal immunization with our short Abeta fragment immunogens and a mucosal adjuvant, mutant Escherichia coli heat-labile enterotoxin LT(R192G), resulted in reduced cerebral Abeta levels, plaque deposition, and gliosis, as well as increased plasma Abeta levels and improved cognition in a transgenic mouse model of AD. Preclinical trials in nonhuman primates, and human clinical trials using similar Abeta immunogens, are now underway. Abeta immunotherapy looks promising but must be made safer and more effective at generating antibody titers in the elderly. It is hoped that these novel immunogens will enhance Abeta antibody generation across a broad population and avoid the adverse events seen in the earlier clinical trial.
International Nuclear Information System (INIS)
López-Requena, Alejandro; Burrone, Oscar R.; Cesco-Gaspere, Michela
2012-01-01
Idiotype (Id)-based immunotherapy has been exploited as cancer treatment option. Conceived as therapy for malignancies bearing idiotypic antigens, it has been also extended to solid tumors because of the capacity of anti-idiotypic antibodies to mimic Id-unrelated antigens. In both these two settings, efforts are being made to overcome the poor immune responsiveness often experienced when using self immunoglobulins as immunogens. Despite bearing a unique gene combination, and thus particular epitopes, it is normally difficult to stimulate the immune response against antibody variable regions. Different strategies are currently used to strengthen Id immunogenicity, such as concomitant use of immune-stimulating molecules, design of Id-containing immunogenic recombinant proteins, specific targeting of relevant immune cells, and genetic immunization. This review focuses on the role of anti-Id vaccination in cancer management and on the current developments used to foster anti-idiotypic B and T cell responses.
Energy Technology Data Exchange (ETDEWEB)
López-Requena, Alejandro [Molecular Immunology Group, International Centre for Genetic Engineering and Biotechnology, Trieste (Italy); Immunobiology Division, Center of Molecular Immunology, Havana (Cuba); Bioengineering Research Institute, Biotech Pharmaceutical Co., Ltd, Beijing (China); Burrone, Oscar R.; Cesco-Gaspere, Michela, E-mail: cescogaspere@gmail.com [Molecular Immunology Group, International Centre for Genetic Engineering and Biotechnology, Trieste (Italy)
2012-11-09
Idiotype (Id)-based immunotherapy has been exploited as cancer treatment option. Conceived as therapy for malignancies bearing idiotypic antigens, it has been also extended to solid tumors because of the capacity of anti-idiotypic antibodies to mimic Id-unrelated antigens. In both these two settings, efforts are being made to overcome the poor immune responsiveness often experienced when using self immunoglobulins as immunogens. Despite bearing a unique gene combination, and thus particular epitopes, it is normally difficult to stimulate the immune response against antibody variable regions. Different strategies are currently used to strengthen Id immunogenicity, such as concomitant use of immune-stimulating molecules, design of Id-containing immunogenic recombinant proteins, specific targeting of relevant immune cells, and genetic immunization. This review focuses on the role of anti-Id vaccination in cancer management and on the current developments used to foster anti-idiotypic B and T cell responses.
Shuhaiber, Jeffrey H
2004-02-01
To evaluate the history and current knowledge of computer-augmented reality in the field of surgery and its potential goals in education, surgeon training, and patient treatment. National Library of Medicine's database and additional library searches. Only articles suited to surgical sciences with a well-defined aim of study, methodology, and precise description of outcome were included. Augmented reality is an effective tool in executing surgical procedures requiring low-performance surgical dexterity; it remains a science determined mainly by stereotactic registration and ergonomics. Strong evidence was found that it is an effective teaching tool for training residents. Weaker evidence was found to suggest a significant influence on surgical outcome, both morbidity and mortality. No evidence of cost-effectiveness was found. Augmented reality is a new approach in executing detailed surgical operations. Although its application is in a preliminary stage, further research is needed to evaluate its long-term clinical impact on patients, surgeons, and hospital administrators. Its widespread use and the universal transfer of such technology remains limited until there is a better understanding of registration and ergonomics.
International Nuclear Information System (INIS)
Xu Wei; Chu Yiwei; Zhang Ruihua; Xu Huanbin; Wang Ying; Xiong Sidong
2005-01-01
CD8 + T cells play a critical role in protective immunity against Hepatitis B Virus (HBV). Epitope-based DNA vaccines expressing HBV-dominant CTL epitopes can be used as candidate vaccines capable of inducing cytotoxic T Lymphocytes (CTL) responses. A plasmid DNA encoding a CTL epitope of HBV core antigen, HBc 18-27 , was constructed. Intramuscular immunization of C57BL/6 mice with this DNA vaccine resulted in successful induction of HBV-specific CTL responses. In order to promote transportation of the peptide into endoplasmic reticulum (ER) to bind to MHC class I molecules for optimal class I antigen presentation, an ER targeting sequence (ERTS) was fused with the C 18-27 encoding gene. ERTS fusion significantly enhanced specific CD8 + T cell responses in terms of CTL cytolysis as well as IFN-γ secretion. This enhancement was correlated with promoted epitope presentation on target cell surface. We report here an enhanced immunogenicity of an epitope-based DNA vaccine using an ER targeting signal sequence, which has significant implications for future design of therapeutic HBV vaccine
Directory of Open Access Journals (Sweden)
Chen Dishi
2011-06-01
Full Text Available Abstract Background Porcine parvovirus (PPV VP2 gene has been successfully expressed in many expression systems resulting in self-assembly of virus-like particles (VLPs with similar morphology to the native capsid. Here, a pseudorabies virus (PRV system was adopted to express the PPV VP2 gene. Methods A recombinant PRV SA215/VP2 was obtained by homologous recombination between the vector PRV viral DNA and a transfer plasmid. Then recombinant virus was purified with plaque purification, and its identity confirmed by PCR amplification, Western blot and indirect immunofluorescence (IFA analyses. Electronic microscopy of PRV SA215/VP2 confirmed self-assembly of both pseudorabies virus and VLPs from VP2 protein. Results Immunization of piglets with recombinant virus elicited PRV-specific and PPV-specific humoral immune responses and provided complete protection against a lethal dose of PRV challenges. Gilts immunized with recombinant viruses induced PPV-specific antibodies, and significantly reduced the mortality rate of (1 of 28 following virulent PPV challenge compared with the control (7 of 31. Furthermore, PPV virus DNA was not detected in the fetuses of recombinant virus immunized gilts. Conclusions In this study, a recombinant PRV SA215/VP2 virus expressing PPV VP2 protein was constructed using PRV SA215 vector. The safety, immunogenicity, and protective efficacy of the recombinant virus were demonstrated in piglets and primiparous gilts. This recombinant PRV SA215/VP2 represents a suitable candidate for the development of a bivalent vaccine against both PRV and PPV infection.
Enhancing tourism with augmented and virtual reality
Jenny, Sandra
2017-01-01
Augmented and virtual reality are on the advance. In the last twelve months, several interesting devices have entered the market. Since tourism is one of the fastest growing economic sectors in the world and has become one of the major players in international commerce, the aim of this thesis was to examine how tourism could be enhanced with augmented and virtual reality. The differences and functional principles of augmented and virtual reality were investigated, general uses were described ...
Zhang, Xiaoguang; Yang, Ren; Wang, Jiao; Wang, Xuan; Hou, Mieling; An, Lina; Zhu, Ying; Cao, Yuxi; Zeng, Yi
2016-01-01
We used 293 cells to express the recombinant membrane protein of the Ebola virus. Then, the immunogenicity of the recombinant protein was studied by immunized BALB/c mice. According to the codon use frequency of humans, the gene encoding the extracellular domain of the Ebola virus membrane protein was optimized, synthesized, and inserted into the eukaryotic expression plasmid pXG-Fc to construct the human IgG Fc and Ebola GP fusion protein expression plasmid pXG-modGP-Fc. To achieve expression, the fusion protein expression vector was transfected into high-density 293 cells using transient transfection technology. The recombinant protein was purified by protein A affinity chromatography. BALB/c mice were immunized with the purified fusion protein, and serum antibody titers evaluated by an indirect enzyme-linked immunosorbent assay (ELISA). Purification and analyses of the protein revealed that the eukaryotic expression vector could express the recombinant protein GP-Fc effectively, and that the recombinant protein in the supernatant of the cell culture was present as a dimer. After immunization with the purified recombinant protein, a high titer of antigen-specific IgG could be detected in the serum of immunized mice by indirect ELISA, showing that the recombinant protein had good immunogenicity. These data suggest that we obtained a recombinant protein with good immunogenicity. Our study is the basis for development of a vaccine against the Ebola virus and for screening of monoclonal antibodies.
Directory of Open Access Journals (Sweden)
Eugene Gu, Wen-Yi Chen, Jay Gu, Paul Burridge, Joseph C. Wu
2012-01-01
Full Text Available Being able to self-renew and differentiate into virtually all cell types, both human embryonic stem cells (hESCs and induced pluripotent stem cells (iPSCs have exciting therapeutic implications for myocardial infarction, neurodegenerative disease, diabetes, and other disorders involving irreversible cell loss. However, stem cell biology remains incompletely understood despite significant advances in the field. Inefficient stem cell differentiation, difficulty in verifying successful delivery to the target organ, and problems with engraftment all hamper the transition from laboratory animal studies to human clinical trials. Although traditional histopathological techniques have been the primary approach for ex vivo analysis of stem cell behavior, these postmortem examinations are unable to further elucidate the underlying mechanisms in real time and in vivo. Fortunately, the advent of molecular imaging has led to unprecedented progress in understanding the fundamental behavior of stem cells, including their survival, biodistribution, immunogenicity, and tumorigenicity in the targeted tissues of interest. This review summarizes various molecular imaging technologies and how they have advanced the current understanding of stem cell survival, biodistribution, immunogenicity, and tumorigenicity.
Breather trapping and breather transmission in a DNA model with an interface
DEFF Research Database (Denmark)
Alvarez, A.; Romero, F.R.; Archilla, J.F.R.
2006-01-01
We study the dynamics of moving discrete breathers in an interfaced piecewise DNA molecule. This is a DNA chain in which all the base pairs are identical and there exists an interface such that the base pairs dipole moments at each side are oriented in opposite directions. The Hamiltonian...... of the Peyrard-Bishop model is augmented with a term that includes the dipole-dipole coupling between base pairs. Numerical simulations show the existence of two dynamical regimes. If the translational kinetic energy of a moving breather launched towards the interface is below a critical value, it is trapped...
Augmented Reality: Daily Prayers for Preschooler Student
Directory of Open Access Journals (Sweden)
Hendra Pradibta
2018-01-01
Full Text Available Education is one of the aspects that many synthesized with technology. Yet, this is contrary to the fact that where most of the learning materials are still based on text. This research aims to develop an alternative learning media by implementing Augmented Reality Technology for Preschooler students. Augmented Reality (AR is an application that can combine the virtual object as text, pictures and animation into the real world. Development of Augmented Reality application uses Web Aurasma Based Studio, with learning materials of daily prayer for preschool student. The development of the characters and the animations were using Adobe Illustrator and Adobe After Effects. The results of the study showed that technology Augmented Reality can be used as an alternative learning media especially in the learning process in Preschool Al Furqon. This is because the content Augmented Reality in the form of animation can gives more understanding and attention for preschool student to follow the learning process
From Augmentation Media to Meme Media.
Tanaka, Yuzuru
Computers as meta media are now evolving from augmentation media vehicles to meme media vehicles. While an augmentation media system provides a seamlessly integrated environment of various tools and documents, meme media system provides further functions to edit and distribute tools and documents. Documents and tools on meme media can easily…
Potential costs of breast augmentation mammaplasty.
Schmitt, William P; Eichhorn, Mitchell G; Ford, Ronald D
2016-01-01
Augmentation mammaplasty is one of the most common surgical procedures performed by plastic surgeons. The aim of this study was to estimate the cost of the initial procedure and its subsequent complications, as well as project the cost of Food and Drug Administration (FDA)-recommended surveillance imaging. The potential costs to the individual patient and society were calculated. Local plastic surgeons provided billing data for the initial primary silicone augmentation and reoperative procedures. Complication rates used for the cost analysis were obtained from the Allergen Core study on silicone implants. Imaging surveillance costs were considered in the estimations. The average baseline initial cost of silicone augmentation mammaplasty was calculated at $6335. The average total cost of primary breast augmentation over the first decade for an individual patient, including complications requiring reoperation and other ancillary costs, was calculated at $8226. Each decade thereafter cost an additional $1891. Costs may exceed $15,000 over an averaged lifetime, and the recommended implant surveillance could cost an additional $33,750. The potential cost of a breast augmentation, which includes the costs of complications and imaging, is significantly higher than the initial cost of the procedure. Level III, economic and decision analysis study. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
The Augmented REality Sandtable (ARES)
2015-10-01
Introduction The US Army Research Laboratory (ARL) Human Sciences Campaign calls out the topic of Virtual /Mixed and Augmented Reality as one of the...type of virtual environment. In virtual reality (VR), the totality of the environment is computer generated. In AR, the real world is augmented by...tangible user interfaces; and the effectiveness of virtual sand tables and similar systems. A market survey was also done to discover the state of
Augmented Reality: Daily Prayers for Preschooler Student
Hendra Pradibta
2018-01-01
Education is one of the aspects that many synthesized with technology. Yet, this is contrary to the fact that where most of the learning materials are still based on text. This research aims to develop an alternative learning media by implementing Augmented Reality Technology for Preschooler students. Augmented Reality (AR) is an application that can combine the virtual object as text, pictures and animation into the real world. Development of Augmented Reality application uses Web Aurasma Ba...
Applied Augmented Reality for High Precision Maintenance
Dever, Clark
Augmented Reality had a major consumer breakthrough this year with Pokemon Go. The underlying technologies that made that app a success with gamers can be applied to improve the efficiency and efficacy of workers. This session will explore some of the use cases for augmented reality in an industrial environment. In doing so, the environmental impacts and human factors that must be considered will be explored. Additionally, the sensors, algorithms, and visualization techniques used to realize augmented reality will be discussed. The benefits of augmented reality solutions in industrial environments include automated data recording, improved quality assurance, reduction in training costs and improved mean-time-to-resolution. As technology continues to follow Moore's law, more applications will become feasible as performance-per-dollar increases across all system components.
Augmented Reality in Tourism - Research and Applications Overview
Directory of Open Access Journals (Sweden)
Anabel L. Kečkeš
2017-06-01
Full Text Available Augmented reality is a complex interdisciplinary field utilizing information technologies in diverse areas such as medicine, education, architecture, industry, tourism and others, augmenting the real-time, real-world view with additional superimposed information in chosen format(s. The aim of this paper is to present an overview of both research and application aspects of using augmented reality technologies in tourism domain. While most research, and especially applications, are dealing with and developing visual-based augmented reality systems, there is a relevant amount of research discussing the utilization of other human senses such as tactioception and audioception, both being discussed within this work. A comprehensive literature analysis within this paper resulted with the identification, compilation and categorization of the key factors having the most relevant impact on the success of utilization of augmented technology in tourism domain.
Sliepen, Kwinten; Ozorowski, Gabriel; Burger, Judith A.; van Montfort, Thijs; Stunnenberg, Melissa; Labranche, Celia; Montefiori, David C.; Moore, John P.; Ward, Andrew B.; Sanders, Rogier W.
2015-01-01
Background: Presenting vaccine antigens in particulate form can improve their immunogenicity by enhancing B cell activation. Findings: We describe ferritin-based protein nanoparticles that display multiple copies of native-like HIV-1 envelope glycoprotein trimers (BG505 SOSIP.664). Trimer-bearing
Size, Shape, and Sequence-Dependent Immunogenicity of RNA Nanoparticles.
Guo, Sijin; Li, Hui; Ma, Mengshi; Fu, Jian; Dong, Yizhou; Guo, Peixuan
2017-12-15
RNA molecules have emerged as promising therapeutics. Like all other drugs, the safety profile and immune response are important criteria for drug evaluation. However, the literature on RNA immunogenicity has been controversial. Here, we used the approach of RNA nanotechnology to demonstrate that the immune response of RNA nanoparticles is size, shape, and sequence dependent. RNA triangle, square, pentagon, and tetrahedron with same shape but different sizes, or same size but different shapes were used as models to investigate the immune response. The levels of pro-inflammatory cytokines induced by these RNA nanoarchitectures were assessed in macrophage-like cells and animals. It was found that RNA polygons without extension at the vertexes were immune inert. However, when single-stranded RNA with a specific sequence was extended from the vertexes of RNA polygons, strong immune responses were detected. These immunostimulations are sequence specific, because some other extended sequences induced little or no immune response. Additionally, larger-size RNA square induced stronger cytokine secretion. 3D RNA tetrahedron showed stronger immunostimulation than planar RNA triangle. These results suggest that the immunogenicity of RNA nanoparticles is tunable to produce either a minimal immune response that can serve as safe therapeutic vectors, or a strong immune response for cancer immunotherapy or vaccine adjuvants. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Duan, Xiao-yi; Wang, Jian-sheng; Guo, You-min; Han, Jun-li; Wang, Quan-ying; Yang, Guang-xiao
2007-01-01
To construct recombinant prokaryotic expression plasmid pET28a(+)/c-PEP-3-c and evaluate the immunogenicity of the fusion protein. cDNA fragment encoding PEP-3 was obtained from pGEM-T Easy/PEP-3 and inserted into recombinant plasmid pGEMEX/HBcAg. Then it was subcloned in prokaryotic expression vector and transformed into E.coli BL21(DE3). The fusion protein was expressed by inducing IPTG and purified by Ni(2+)-NTA affinity chromatography. BALB/c mice were immunized with fusion protein and the antibody titre was determined by indirect ELISA. The recombinant gene was confirmed to be correct by restriction enzyme digestion and DNA sequencing. After prokaryotic expression, fusion protein existed in sediment and accounted for 56% of all bacterial lysate. The purified product accounted for 92% of all protein and its concentration was 8 g/L. The antibody titre in blood serum reached 1:16 000 after the fourth immunization and reached 1:2.56x10(5) after the sixth immunization. The titre of anti-PEP-3 antibody reached 1:1.28x10(5) and the titre of anti-HBcAg antibody was less than 1:4x10(3). Fusion gene PEP-3-HBcAg is highly expressed in E.coli BL21. The expressed fusion protein can induce neutralizing antibody with high titer and specificity, which lays a foundation for the study of genetically engineering vaccine for malignant tumors with the high expression of EGFRvIII.
International Nuclear Information System (INIS)
Gasparini, R.; Pozzi, T.; Montomoli, E.; Fragapane, E.; Senatore, F.; Minutello, M.; Podda, A.
2001-01-01
Three-hundred and eight outpatient elderly subjects (≥ 65 years) were randomly assigned to receive the MF59-adjuvanted influenza vaccine (FLUAD; n = 204) or a conventional subunit influenza vaccine (AGRIPPAL S1; n = 104) in order to compare the safety and immunogenicity of the two vaccines. Although mild pain at the injection site was reported more frequently by subjects immunised with the adjuvanted vaccine, both vaccines were shown to be safe and well tolerated. The adjuvanted vaccine was more immunogenic as indicated by higher post-immunisation geometric mean titres (GMTs) and by higher proportions of subjects with post-immunisation ≥ four fold increases of antibody titres or subjects with ≥ 1/160 post-immunisation HI titres. These differences, statistically significant for all three strains after immunisation, indicated that, by addition of the MF59 adjuvant emulsion, conventional subunit influenza antigens acquire an enhanced immunogenicity without any clinically significant increase of their reactogenicity
Effects of industrial processing on the immunogenicity of commonly ingested fish species.
Sletten, Gaynour; Van Do, Thien; Lindvik, Helene; Egaas, Eliann; Florvaag, Erik
2010-01-01
Food-processing techniques may induce changes in fish protein immunogenicity. Allergens from >100 fish species have been identified, but little is known on the effects of processing on fish protein immunogenicity. IgE binding of sera of patients allergic to fresh and processed (smoked, salted/sugar-cured, canned, lye-treated and fermented) cod, haddock, salmon, trout, tuna, mackerel and herring and of hydrolysates based on salmon and whiting was investigated using immunoblot and inhibition ELISA. Parvalbumin oligomers were identified using monoclonal and polyclonal antibodies. IgE binding was seen in most sera at 12-14 kDa (parvalbumin), and at 17-60 kDa for all fish except tuna. Changes in IgE binding appeared to reflect altered parvalbumin monomers and oligomers. Smoked haddock, salmon and mackerel had increased IgE binding and novel bands at 30 kDa. Chemically processed cod, salmon, trout and pickled herring had reduced or abolished IgE binding. The serum of 1 subject, however, had increased IgE binding to these products and also inhibition of binding by both fish hydrolysates to their constituent fish species. Process-induced changes in fish protein immunogenicity were more dependent on process rather than species, although individual responses varied. Changes in the allergenicity of a product may depend on the net effect of processing on parvalbumin oligomerization patterns, which may also vary in different species. Chemical processes generally caused loss in IgE-binding activity, though sensitization may occur to modified or degraded rather than intact peptides as shown by increased binding by chemically processed fish and hydrolysates in 1 subject. The clinical significance of these findings remains to be established.
Immunogenicity of biopharmaceuticals and biosimilars in relation to storage, handling and stability
International Nuclear Information System (INIS)
Hincal, F.
2009-01-01
Therapeutic proteins or biopharmaceuticals provide effective treatment for many diseases and medical conditions, and vaccines, immunoglobulins and monoclonal antibodies are critical biodefense biopharmaceuticals which constitute an indispensable part of biodefense stockpiles. The manufacturing process for biopharmaceuticals and their generic forms which are called biosimilars is far more complex than for low molecular weight drugs and generics. Any minor change made at any stage may have a critical effect on the clinical efficacy and safety. Potential immunogenicity is the key issue for biopharmaceuticals and biosimilars and may have serious clinical consequences ranging from allergy and anaphylaxis, as well as loss of efficacy of the product. Immunogenicity may be influenced by factors related to manufacturing process, formulation, aggregate formation, contaminants and impurities, and also by the factors related to the storage and handling. Stability is particularly important with larger protein molecules, because their in vivo effects often depend on their three-dimensional structure. Proteins usually aggregate from partially unfolded molecules and aggregates can enhance immunogenicity. Although product formulations are developed to maximize and maintain the fraction of the protein molecules present in the native state, significant amounts of aggregates can form, especially over pharmaceutically relevant time scales and under stress conditions. Exposure to air-liquid and solid-liquid interfaces, light, temperature fluctuations or minor impurities can induce aggregation. Such exposure can occur during processing steps, as well as in the final product container during storage, shipment and handling. Biopharmaceuticals are particularly sensitive to temperature changes and/or shaking. Strict storage and handling conditions and timely and effective stability/shelf-life testing are therefore essential for maintaining product integrity and stability, and hence efficacy
Alternative realities : from augmented reality to mobile mixed reality
Claydon, Mark
2015-01-01
This thesis provides an overview of (mobile) augmented and mixed reality by clarifying the different concepts of reality, briefly covering the technology behind mobile augmented and mixed reality systems, conducting a concise survey of existing and emerging mobile augmented and mixed reality applications and devices. Based on the previous analysis and the survey, this work will next attempt to assess what mobile augmented and mixed reality could make possible, and what related applications an...
... page: //medlineplus.gov/ency/presentations/100009.htm Chin augmentation - series—Normal anatomy To use the sharing features ... Bethesda, MD 20894 U.S. Department of Health and Human Services National Institutes of Health Page last updated: ...
Breast augmentation - slideshow
... page: //medlineplus.gov/ency/presentations/100205.htm Breast augmentation - series—Normal anatomy To use the sharing features ... Bethesda, MD 20894 U.S. Department of Health and Human Services National Institutes of Health Page last updated: ...
Critical review: assessment of interferon-β immunogenicity in multiple sclerosis
DEFF Research Database (Denmark)
Bendtzen, Klaus
2010-01-01
This review discusses type I interferon (IFN) immunogenicity with focus on methods of detection of anti-IFN antibodies in patients treated with human recombinant IFN-β. Pitfalls involved in the clinical use of various types of assays for binding antibodies and neutralizing antibodies against IFN-...... for individualized or personalized medicine, ie, optimizing therapies according to individual needs rather than using standardized trial-and-error regimens to all patients, is highlighted....
Critical review: assessment of interferon-ß immunogenicity in multiple sclerosis
DEFF Research Database (Denmark)
Bendtzen, Klaus
2010-01-01
This review discusses type I interferon (IFN) immunogenicity with focus on methods of detection of anti-IFN antibodies in patients treated with human recombinant IFN-ß. Pitfalls involved in the clinical use of various types of assays for binding antibodies and neutralizing antibodies against IFN-...... for individualized or personalized medicine, ie, optimizing therapies according to individual needs rather than using standardized trial-and-error regimens to all patients, is highlighted....
Strobel, S; Ferguson, A; Anderson, D M
1986-01-01
An animal model has been used to investigate the immunogenicity and non-specific irritant properties of exudate gums. The materials studied were four preparations of gum arabic (Acacia spp.), two of gum karaya (Sterculia spp.), two of gum tragacanth (Astralagus spp.) and a residue obtained after ethanol extraction of gum arabic. Groups of animals were intradermally immunized with the gum in complete Freund's adjuvant. Serum antibody levels were measured by an ELISA technique and delayed hypersensitivity responses by a footpad swelling test. Antigenic cross-reactivity within each gum species was tested in a crossover fashion. All gum preparations elicited systemic immune responses after immunization. Further processing reduced immunogenicity, although there was no evidence that systemic immunity to these complex polysaccharide antigens responses could be completely abolished by processing or purification. The ethanolic extract, and some of the gum preparations, particularly tragacanth and karaya, caused considerable footpad swelling when injected intradermally. It is concluded that processing and awareness of subspecies differences can reduce the inherent immunogenicity and potential irritant effects of exudate gums.
Augmented reality-assisted skull base surgery.
Cabrilo, I; Sarrafzadeh, A; Bijlenga, P; Landis, B N; Schaller, K
2014-12-01
Neuronavigation is widely considered as a valuable tool during skull base surgery. Advances in neuronavigation technology, with the integration of augmented reality, present advantages over traditional point-based neuronavigation. However, this development has not yet made its way into routine surgical practice, possibly due to a lack of acquaintance with these systems. In this report, we illustrate the usefulness and easy application of augmented reality-based neuronavigation through a case example of a patient with a clivus chordoma. We also demonstrate how augmented reality can help throughout all phases of a skull base procedure, from the verification of neuronavigation accuracy to intraoperative image-guidance. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Human monoclonal antibodies: the residual challenge of antibody immunogenicity.
Waldmann, Herman
2014-01-01
One of the major reasons for seeking human monoclonal antibodies has been to eliminate immunogenicity seen with rodent antibodies. Thus far, there has yet been no approach which absolutely abolishes that risk for cell-binding antibodies. In this short article, I draw attention to classical work which shows that monomeric immunoglobulins are intrinsically tolerogenic if they can be prevented from creating aggregates or immune complexes. Based on these classical studies two approaches for active tolerization to therapeutic antibodies are described.
Enhancing Education through Mobile Augmented Reality
Joan, D. R. Robert
2015-01-01
In this article, the author has discussed about the Mobile Augmented Reality and enhancing education through it. The aim of the present study was to give some general information about mobile augmented reality which helps to boost education. Purpose of the current study reveals the mobile networks which are used in the institution campus as well…
Augmented Reality as a Countermeasure for Sleep Deprivation.
Baumeister, James; Dorrlan, Jillian; Banks, Siobhan; Chatburn, Alex; Smith, Ross T; Carskadon, Mary A; Lushington, Kurt; Thomas, Bruce H
2016-04-01
Sleep deprivation is known to have serious deleterious effects on executive functioning and job performance. Augmented reality has an ability to place pertinent information at the fore, guiding visual focus and reducing instructional complexity. This paper presents a study to explore how spatial augmented reality instructions impact procedural task performance on sleep deprived users. The user study was conducted to examine performance on a procedural task at six time points over the course of a night of total sleep deprivation. Tasks were provided either by spatial augmented reality-based projections or on an adjacent monitor. The results indicate that participant errors significantly increased with the monitor condition when sleep deprived. The augmented reality condition exhibited a positive influence with participant errors and completion time having no significant increase when sleep deprived. The results of our study show that spatial augmented reality is an effective sleep deprivation countermeasure under laboratory conditions.
Initial Model of Social Acceptability for Human Augmentation Technologies
Eghtebas, Chloe; Pay, Yun Suen; Väänänen, Kaisa; Pfeiffer, Ties; Meyer, Joachim; Lukosch, S.G.
2017-01-01
Academia and industry engage in major efforts to develop technologies for augmenting human senses and activities. Many of these technologies, such as augmented reality (AR) and virtual reality (VR) head mounted displays (HMD), haptic augmentation systems, and exoskeletons can be applied in numerous
Media-Augmented Exercise Machines
Krueger, T.
2002-01-01
Cardio-vascular exercise has been used to mitigate the muscle and cardiac atrophy associated with adaptation to micro-gravity environments. Several hours per day may be required. In confined spaces and long duration missions this kind of exercise is inevitably repetitive and rapidly becomes uninteresting. At the same time, there are pressures to accomplish as much as possible given the cost- per-hour for humans occupying orbiting or interplanetary. Media augmentation provides a the means to overlap activities in time by supplementing the exercise with social, recreational, training or collaborative activities and thereby reducing time pressures. In addition, the machine functions as an interface to a wide range of digital environments allowing for spatial variety in an otherwise confined environment. We hypothesize that the adoption of media augmented exercise machines will have a positive effect on psycho-social well-being on long duration missions. By organizing and supplementing exercise machines, data acquisition hardware, computers and displays into an interacting system this proposal increases functionality with limited additional mass. This paper reviews preliminary work on a project to augment exercise equipment in a manner that addresses these issues and at the same time opens possibilities for additional benefits. A testbed augmented exercise machine uses a specialty built cycle trainer as both input to a virtual environment and as an output device from it using spatialized sound, and visual displays, vibration transducers and variable resistance. The resulting interactivity increases a sense of engagement in the exercise, provides a rich experience of the digital environments. Activities in the virtual environment and accompanying physiological and psychological indicators may be correlated to track and evaluate the health of the crew.
DEFF Research Database (Denmark)
Christner, Martin; Heinze, Constanze; Busch, Michael
2012-01-01
to biofilm formation in mutant 1585ΔsarA. Increased eDNA amounts indirectly resulted from upregulation of metalloprotease SepA, leading to boosted processing of autolysin AtlE, in turn inducing augmented autolysis and release of eDNA. Hence, this study identifies sarA as a negative regulator of Embp‐ and e...
Santi, Luca; Batchelor, Lance; Huang, Zhong; Hjelm, Brooke; Kilbourne, Jacquelyn; Arntzen, Charles J; Chen, Qiang; Mason, Hugh S
2008-03-28
Virus-like particles (VLPs) derived from enteric pathogens like Norwalk virus (NV) are well suited to study oral immunization. We previously described stable transgenic plants that accumulate recombinant NV-like particles (rNVs) that were orally immunogenic in mice and humans. The transgenic approach suffers from long generation time and modest level of antigen accumulation. We now overcome these constraints with an efficient tobacco mosaic virus (TMV)-derived transient expression system using leaves of Nicotiana benthamiana. We produced properly assembled rNV at 0.8 mg/g leaf 12 days post-infection (dpi). Oral immunization of CD1 mice with 100 or 250 microg/dose of partially purified rNV elicited systemic and mucosal immune responses. We conclude that the plant viral transient expression system provides a robust research tool to generate abundant quantities of rNV as enriched, concentrated VLP preparations that are orally immunogenic.
Augmented reality: dé nieuwe dimensie in de sport?
Slender, Hans
2010-01-01
Volgens trendwatcher Justien Marseille de trend van 2010: augmented reality. Augmented reality is een techniek om met de computer gemaakte beelden toe te voegen aan de realiteit. Het Nederlandse Layar (layar.com) presenteerde zich vorig jaar vol trots als een unieke augmented reality browser, met
Augmentation of Radiation Response by Panitumumab in Models of Upper Aerodigestive Tract Cancer
International Nuclear Information System (INIS)
Kruser, Tim J.; Armstrong, Eric A.; Ghia, Amol J.; Huang Shyhmin; Wheeler, Deric L.; Radinsky, Robert; Freeman, Daniel J.; Harari, Paul M.
2008-01-01
Purpose: To examine the interaction between panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody, and radiation in head-and-neck squamous cell carcinoma and non-small-cell lung cancer cell lines and xenografts. Methods and Materials: The head-and-neck squamous cell carcinoma lines UM-SCC1 and SCC-1483, as well as the non-small-cell lung cancer line H226, were studied. Tumor xenografts in athymic nude mice were used to assess the in vivo activity of panitumumab alone and combined with radiation. In vitro assays were performed to assess the effect of panitumumab on radiation-induced cell signaling, apoptosis, and DNA damage. Results: Panitumumab increased the radiosensitivity as measured by the clonogenic survival assay. Radiation-induced epidermal growth factor receptor phosphorylation and downstream signaling through mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) was inhibited by panitumumab. Panitumumab augmented radiation-induced DNA damage by 1.2-1.6-fold in each of the cell lines studied as assessed by residual γ-H 2 AX foci after radiation. Radiation-induced apoptosis was increased 1.4-1.9-fold by panitumumab, as evidenced by Annexin V-fluorescein isothiocyanate staining and flow cytometry. In vivo, the combination therapy of panitumumab and radiation was superior to panitumumab or radiation alone in the H226 xenografts (p = 0.01) and showed a similar trend in the SCC-1483 xenografts (p = 0.08). In vivo, immunohistochemistry demonstrated the ability of panitumumab to augment the antiproliferative and antiangiogenic effects of radiation. Conclusion: These studies have identified a favorable interaction in the combination of radiation and panitumumab in upper aerodigestive tract tumor models, both in vitro and in vivo. These data suggest that clinical investigations examining the combination of radiation and panitumumab in the treatment of epithelial tumors warrant
Highly immunogenic and fully synthetic peptide-carrier constructs targetting GnRH
DEFF Research Database (Denmark)
Beekman, N.J.C.M.; Schaaper, W.M.M.; Turkstra, J.A.
1999-01-01
To use peptides as synthetic vaccines, they have to be coupled to a carrier protein to make them more immunogenic. Coupling efficiency between a carrier protein and a peptide, however, is difficult to control with respect to loading density of the peptide, This makes these carrier proteins poorly...... for the induction of antibodies against GnRH and immunocastration of pigs....
Directory of Open Access Journals (Sweden)
Tomáš Koubek
2013-01-01
Full Text Available We assume that one of the key reasons is in the difference between a standalone application and a web service. Both architectures have some advantages and disadvantages. The Standalone application (e.g. Nokia/OVI Maps provides the required functionality. From the user point of view, main asset of this “offline” approach is network connectivity independence. However, this kind of applications must be upgraded manually. Moreover, it is hard to get any data about the application usage because it requires additional actions from the user – data are usually acquired through conventional ways, such as email or web forms.The online service such as Google Maps (including its mobile application can offer the same functionality as the offline application. Nevertheless, a permanent connection to provider servers is necessary. This can be taken as a drawback. On the other hand, usage data collection is easier and can be done without the user intervention. The data collection provides a valuable analysis basis of the user habits and needs. This analysis is necessary for design of a complex “user” based solutions such as Google Now.Augmented reality applications are usually based on the first mentioned approach. In this article, we describe our model of augmented reality as a service and compare its features with standalone solutions. Further, other important key aspects for large emergence of augmented reality services in a mainstream market are discussed.
Immunogenicity of 60 novel latency-related antigens of Mycobacterium tuberculosis.
Serra-Vidal, Mᵃdel Mar; Latorre, Irene; Franken, Kees L C M; Díaz, Jéssica; de Souza-Galvão, Maria Luiza; Casas, Irma; Maldonado, José; Milà, Cèlia; Solsona, Jordi; Jimenez-Fuentes, M Ángeles; Altet, Neus; Lacoma, Alícia; Ruiz-Manzano, Juan; Ausina, Vicente; Prat, Cristina; Ottenhoff, Tom H M; Domínguez, José
2014-01-01
The aim of our work here was to evaluate the immunogenicity of 60 mycobacterial antigens, some of which have not been previously assessed, notably a novel series of in vivo-expressed Mycobacterium tuberculosis (IVE-TB) antigens. We enrolled 505 subjects and separated them in individuals with and without latent tuberculosis infection (LTBI) vs. patients with active tuberculosis (TB). Following an overnight and 7 days stimulation of whole blood with purified recombinant M. tuberculosis antigens, interferon-γ (IFN-γ) levels were determined by ELISA. Several antigens could statistically significantly differentiate the groups of individuals. We obtained promising antigens from all studied antigen groups [dormancy survival regulon (DosR regulon) encoded antigens; resuscitation-promoting factors (Rpf) antigens; IVE-TB antigens; reactivation associated antigens]. Rv1733, which is a probable conserved transmembrane protein encoded in DosR regulon, turned out to be very immunogenic and able to discriminate between the three defined TB status, thus considered a candidate biomarker. Rv2389 and Rv2435n, belonging to Rpf family and IVE-TB group of antigens, respectively, also stood out as LTBI biomarkers. Although more studies are needed to support our findings, the combined use of these antigens would be an interesting approach to TB immunodiagnosis candidates.
Immunogenicity of 60 novel latency-related antigens of Mycobacterium tuberculosis
Directory of Open Access Journals (Sweden)
Mªdel Mar eSerra Vidal
2014-10-01
Full Text Available The aim of our work here was to evaluate the immunogenicity of 60 mycobacterial antigens, some of which have not been previously assessed, notably a novel series of in vivo-expressed M.tuberculosis (IVE-TB antigens. We enrolled 505 subjects and separated them in individuals with and without latent tuberculosis infection (LTBI versus patients with active tuberculosis. Following an overnight and 7 day stimulation of whole blood with purified recombinant M.tb antigens, interferon-γ (IFN-γ levels were determined by ELISA. Several antigens could statistically significantly differentiate the groups of individuals. We obtained promising antigens from all studied antigen groups (DosR regulon encoded antigens; resuscitation-promoting factors (Rpf antigens; IVE-TB antigens; reactivation asociated antigens. Rv1733, which is a probable conserved transmembrane protein encoded in DosR regulon, turned out to be very immunogenic and able to discriminate between the three defined TB status, thus considered a candidate biomarker. Rv2389 and Rv2435n, belonging to Rpf family and IVE-TB group of antigens, respectively, also stood out as LTBI biomarkers. Although more studies are needed to support our findings, the combined use of these antigens would be an interesting approach to tuberculosis immunodiagnosis candidates.
The convergence of radiation and immunogenic cell death signaling pathways
International Nuclear Information System (INIS)
Golden, Encouse B.; Pellicciotta, Ilenia; Demaria, Sandra; Barcellos-Hoff, Mary H.; Formenti, Silvia C.
2012-01-01
Ionizing radiation (IR) triggers programmed cell death in tumor cells through a variety of highly regulated processes. Radiation-induced tumor cell death has been studied extensively in vitro and is widely attributed to multiple distinct mechanisms, including apoptosis, necrosis, mitotic catastrophe (MC), autophagy, and senescence, which may occur concurrently. When considering tumor cell death in the context of an organism, an emerging body of evidence suggests there is a reciprocal relationship in which radiation stimulates the immune system, which in turn contributes to tumor cell kill. As a result, traditional measurements of radiation-induced tumor cell death, in vitro, fail to represent the extent of clinically observed responses, including reductions in loco-regional failure rates and improvements in metastases free and overall survival. Hence, understanding the immunological responses to the type of radiation-induced cell death is critical. In this review, the mechanisms of radiation-induced tumor cell death are described, with particular focus on immunogenic cell death (ICD). Strategies combining radiotherapy with specific chemotherapies or immunotherapies capable of inducing a repertoire of cancer specific immunogens might potentiate tumor control not only by enhancing cell kill but also through the induction of a successful anti-tumor vaccination that improves patient survival.
Recent Development of Augmented Reality in Surgery: A Review
Vávra, P.; Zonča, P.; Ihnát, P.; El-Gendi, A.
2017-01-01
Introduction The development augmented reality devices allow physicians to incorporate data visualization into diagnostic and treatment procedures to improve work efficiency, safety, and cost and to enhance surgical training. However, the awareness of possibilities of augmented reality is generally low. This review evaluates whether augmented reality can presently improve the results of surgical procedures. Methods We performed a review of available literature dating from 2010 to November 2016 by searching PubMed and Scopus using the terms “augmented reality” and “surgery.” Results. The initial search yielded 808 studies. After removing duplicates and including only journal articles, a total of 417 studies were identified. By reading of abstracts, 91 relevant studies were chosen to be included. 11 references were gathered by cross-referencing. A total of 102 studies were included in this review. Conclusions The present literature suggest an increasing interest of surgeons regarding employing augmented reality into surgery leading to improved safety and efficacy of surgical procedures. Many studies showed that the performance of newly devised augmented reality systems is comparable to traditional techniques. However, several problems need to be addressed before augmented reality is implemented into the routine practice. PMID:29065604
Recent Development of Augmented Reality in Surgery: A Review
Directory of Open Access Journals (Sweden)
P. Vávra
2017-01-01
Full Text Available Introduction. The development augmented reality devices allow physicians to incorporate data visualization into diagnostic and treatment procedures to improve work efficiency, safety, and cost and to enhance surgical training. However, the awareness of possibilities of augmented reality is generally low. This review evaluates whether augmented reality can presently improve the results of surgical procedures. Methods. We performed a review of available literature dating from 2010 to November 2016 by searching PubMed and Scopus using the terms “augmented reality” and “surgery.” Results. The initial search yielded 808 studies. After removing duplicates and including only journal articles, a total of 417 studies were identified. By reading of abstracts, 91 relevant studies were chosen to be included. 11 references were gathered by cross-referencing. A total of 102 studies were included in this review. Conclusions. The present literature suggest an increasing interest of surgeons regarding employing augmented reality into surgery leading to improved safety and efficacy of surgical procedures. Many studies showed that the performance of newly devised augmented reality systems is comparable to traditional techniques. However, several problems need to be addressed before augmented reality is implemented into the routine practice.
Kinnear, Ekaterina; Caproni, Lisa J; Tregoning, John S
2015-01-01
DNA vaccines can be manufactured cheaply, easily and rapidly and have performed well in pre-clinical animal studies. However, clinical trials have so far been disappointing, failing to evoke a strong immune response, possibly due to poor antigen expression. To improve antigen expression, improved technology to monitor DNA vaccine transfection efficiency is required. In the current study, we compared plasmid encoded tdTomato, mCherry, Katushka, tdKatushka2 and luciferase as reporter proteins for whole animal in vivo imaging. The intramuscular, subcutaneous and tattooing routes were compared and electroporation was used to enhance expression. We observed that overall, fluorescent proteins were not a good tool to assess expression from DNA plasmids, with a highly heterogeneous response between animals. Of the proteins used, intramuscular delivery of DNA encoding either tdTomato or luciferase gave the clearest signal, with some Katushka and tdKatushka2 signal observed. Subcutaneous delivery was weakly visible and nothing was observed following DNA tattooing. DNA encoding haemagglutinin was used to determine whether immune responses mirrored visible expression levels. A protective immune response against H1N1 influenza was induced by all routes, even after a single dose of DNA, though qualitative differences were observed, with tattooing leading to high antibody responses and subcutaneous DNA leading to high CD8 responses. We conclude that of the reporter proteins used, expression from DNA plasmids can best be assessed using tdTomato or luciferase. But, the disconnect between visible expression level and immunogenicity suggests that in vivo whole animal imaging of fluorescent proteins has limited utility for predicting DNA vaccine efficacy.
Vassilieva, Elena V.; Kalluri, Haripriya; McAllister, Devin; Taherbhai, Misha T.; Esser, E. Stein; Pewin, Winston P.; Pulit-Penaloza, Joanna A.; Prausnitz, Mark R.; Compans, Richard W.; Skountzou, Ioanna
2015-01-01
Prevention of seasonal influenza epidemics and pandemics relies on widespread vaccination coverage to induce protective immunity. In addition to a good antigenic match with the circulating viruses, the effectiveness of individual strains represented in the trivalent vaccines depends on their immunogenicity. In this study we evaluated the immunogenicity of H1N1, H3N2 and B seasonal influenza virus vaccine strains delivered individually with a novel dissolving microneedle patch and the stability of this formulation during storage at 25°C. Our data demonstrate that all strains retained their antigenic activity after incorporation in the dissolving patches as measured by SRID assay and immune responses to vaccination in BALB/c mice. After a single immunization all three antigens delivered with microneedle patches induced superior neutralizing antibody titers compared to intramuscular immunization. Cutaneous antigen delivery was especially beneficial for the less immunogenic B strain. Mice immunized with dissolving microneedle patches encapsulating influenza A/Brisbane/59/07 (H1N1) vaccine were fully protected against lethal challenge by homologous mouse-adapted influenza virus. All vaccine components retained activity during storage at room temperature for at least three months as measured in vitro by SRID assay and in vivo by mouse immunization studies. Our data demonstrate that dissolving microneedle patches are a promising advance for influenza cutaneous vaccination due to improved immune responses using less immunogenic influenza antigens and enhanced stability. PMID:25895053
Age grouping to optimize augmentation success.
Gordon, Robert W
2010-05-01
This article has described the different age groups that present for noninvasive injectable lip and perioral augmentation, as well as the breakdown of 3 subgroups that present within the 4 general age groups. With the fundamental understanding of these presenting groups and subgroups, the practicing augmenter will be able to better treatment plan and educate the patient on realistic and optimal aesthetic outcomes.
Augmented REality Sandtables (ARESs) Impact on Learning
2016-07-01
ARL-CR-0803 ● JULY 2016 US Army Research Laboratory Augmented REality Sandtable’s (ARES’s) Impact on Learning by Tarah N......The use of augmented reality (AR) to supplement training tools, specifically sand tables, can produce highly effective systems at relatively low
Virtual and augmented reality for training on maintenance
International Nuclear Information System (INIS)
Gonzalez, F.
2001-01-01
This paper presents two projects focused to support training on maintenance using new technologies. Both projects aims at specifying. designing, developing, and demonstrating prototypes allowing computer guided maintenance of complex mechanical elements using Virtual Reality (VIRMAN) and Augmented Reality (STARMATE) techniques. VIRMAN project is dedicated to training course development on maintenance using Virtual Reality. It based in the animation of three dimension images for component assembly/de-assembly or equipment movements. STARMATE will rely on Augmented Reality techniques which is a growing area in virtual Reality research. The idea of Augmented Reality is to combine a real scene, viewed by the user, with a virtual scene generated by a computer augmenting the reality with additional information. (Author)
Non-immunogenic, hydrophilic/cationic block copolymers and uses thereof
Scales, Charles W.; Huang, Faqing; McCormick, Charles L.
2010-05-18
The present invention provides novel non-immunogenic, hydrophilic/cationic block copolymers comprising a neutral-hydrophilic polymer and a cationic polymer, wherein both polymers have well-defined chain-end functionality. A representative example of such a block copolymer comprises poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA) and poly(N-[3-(dimethylamino)propyl]methacrylamide) (PDMAPMA). Also provided is a synthesis method thereof in aqueous media via reversible addition fragmentation chain transfer (RAFT) polymerization. Further provided are uses of these block copolymers as drug delivery vehicles and protection agents.
Immunogenicity of peptides of measles virus origin and influence of adjuvants.
Halassy, Beata; Mateljak, Sanja; Bouche, Fabienne B; Pütz, Mike M; Muller, Claude P; Frkanec, Ruza; Habjanec, Lidija; Tomasić, Jelka
2006-01-12
Epitope-based peptide antigens have been under development for protection against measles virus. The immunogenicity of five peptides composed of the same B cell epitope (BCE) (H236-250 of the measles virus hemagglutinin), and different T cell epitopes of measles virus fusion protein (F421-435, F256-270, F288-302) and nucleoprotein (NP335-345) was studied in mice (subcutaneous immunisation). The adjuvant effects of peptidoglycan monomer (PGM), Montanide ISA 720 and 206 were also investigated. Results showed basic differences in peptide immunogenicity that were consistent with already described structural differences. PGM elevated peptide-specific IgG when applied together with four of five tested peptides. A strong synergistic effect was observed after co-immunisation of mice with a mixture containing all five chimeric peptides in small and equal amounts. Results revealed for the first time that immunisation with several peptides having the common BCE generated significantly higher levels of both anti-peptide and anti-BCE IgG in comparison to those obtained after immunisation with a single peptide in much higher quantity. Further improvement of immune response was obtained after incorporation of such a peptide mixture into oil-based adjuvants.
Wichert, R.; Balfanz, D.
2003-01-01
ARVIKA uses augmented reality (AR) technologies to research and create a user-oriented and system-driven support of operation procedures. It focuses on the development, production, and service of complex technical products and systems. Augmented-reality technologies improve working environments by merging real objects with computer-generated virtual objects to allow for detailed engineering and processing instructions. Augmented reality is a novel approach to the interaction between human and...
Feng, Gai-feng; Wang, Jun-yang; Jin, Hui; Wang, Wei-xi; Qian, Yi-hua; Yang, Wei-na; Wang, Quan-ying; Yang, Guang-xiao
2011-11-01
To construct the recombinant prokaryotic expression plasmid pET/c-ABCSP-Aβ(15-c);, and evaluate the immunogenicity of the fusion protein expressed in E.coli. The gene fragment HBc88-144 was amplified by PCR and subcloned to pUC19. The APP beta cleavage site peptide(ABCSP) and Aβ(1-15); gene(ABCSP-Aβ(15);) was amplified by PCR and inserted downstream of HBc1-71 in pGEMEX/c1-71. After restriction enzyme digestion, c1-17-ABCSP-Aβ(15); were connected with HBc88-144, yielding the recombinant gene c-ABCSP-Aβ(15-c);. c-ABCSP-Aβ(15-c); gene was subcloned into pET-28a(+).The fusion protein expressed in transformed E.coli BL21 was induced with IPTG and analyzed by SDS-PAGE. The virus-like particles (VLP) formed by fusion protein was observed with Transmission Electron Microscope (TEM). 4 Kunming (KM) mice received intraperitoneal injection (i.p) of fusion protein VLP. The antibody was detected by indirect ELISA. The recombinant gene was confirmed by restriction enzyme digestion and DNA sequencing. After IPTG induction, fusion protein was expressed and mainly existed in the sediment of the bacterial lysate. The expression level was 40% of all the proteins in the sediment. The fusion protein could form VLP. After 5 times of immunization, the titer of anti-ABCSP and anti-Aβantibody in sera of KM mice reached up to 1:5 000 and 1:10 000 respectively, while the anti-HBc antibody was undetectable. Recombinant c-ABCSP-Aβ(15-c); gene can be expressed in E.coli. The expressed protein could form VLP and has a strong immunogenicity. This study lays the foundation for the study of AD genetic engineering vaccine.
Guidelines for user interactions in mobile augmented reality
Ortman, Erik; Swedlund, Kenneth
2012-01-01
Over the last couple of years the field of Augmented Reality has transformed from something mainly seen in academic researchinto several examples of big commercially successful products, and the widespread use of highly capable mobile devices has greatly helped accelerate this trend. The powerful sensors in modern handsets enable designers to bring Augmented Reality implementations to the hands ofthe users.This thesis examines how Augmented Reality can be implemented onmobile platforms, mainl...
Directory of Open Access Journals (Sweden)
Sara Carbonetti
Full Text Available We evaluated four gp140 Envelope protein vaccine immunogens that were derived from an elite neutralizer, subject VC10042, whose plasma was able to potently neutralize a wide array of genetically distinct HIV-1 isolates. We sought to determine whether soluble Envelope proteins derived from the viruses circulating in VC10042 could be used as immunogens to elicit similar neutralizing antibody responses by vaccination. Each gp140 was tested in its trimeric and monomeric forms, and we evaluated two gp140 trimer vaccine regimens in which adjuvant was supplied at all four immunizations or at only the first two immunizations. Interestingly, all four Envelope immunogens elicited high titers of cross-reactive antibodies that recognize the variable regions V1V2 and are potentially similar to antibodies linked with a reduced risk of HIV-1 acquisition in the RV144 vaccine trial. Two of the four immunogens elicited neutralizing antibody responses that neutralized a wide array of HIV-1 isolates from across genetic clades, but those responses were of very low potency. There were no significant differences in the responses elicited by trimers or monomers, nor was there a significant difference between the two adjuvant regimens. Our study identified two promising Envelope immunogens that elicited anti-V1V2 antibodies and broad, but low potency, neutralizing antibody responses.
Safety and immunogenicity of HIV-1 Tat toxoid in immunocompromised HIV-1-infected patients.
Gringeri, A; Santagostino, E; Muça-Perja, M; Mannucci, P M; Zagury, J F; Bizzini, B; Lachgar, A; Carcagno, M; Rappaport, J; Criscuolo, M; Blattner, W; Burny, A; Gallo, R C; Zagury, D
1998-01-01
To antagonize the deleterious effects of the HIV-1 toxin extracellular Tat on uninfected immune cells, we developed a new strategy of anti-HIV-1 vaccine using an inactivated but immunogenic Tat (Tat toxoid). Tat toxoid has been assayed for safety and immunogenicity in seropositive patients. The phase I vaccine clinical trial testing Tat toxoid preparation in Seppic Isa 51 oil adjuvant was performed on 14 HIV-1-infected asymptomatic although biologically immunocompromised individuals (500-200 CD4+ cells/mm3). Following as many as 8 injections, no clinical defects were observed. All patients exhibited an antibody (Ab) response to Tat, and some had cell-mediated immunity (CMI) as evaluated by skin test in vivo and T-cell proliferation in vitro. These results provide initial evidence of safety and potency of Tat toxoid vaccination in HIV-1-infected individuals.
An experimental test of alternative population augmentation scenarios.
Kronenberger, John A; Gerberich, Jill C; Fitzpatrick, Sarah W; Broder, E Dale; Angeloni, Lisa M; Funk, W Chris
2018-01-19
Human land use is fragmenting habitats worldwide and inhibiting dispersal among previously connected populations of organisms, often leading to inbreeding depression and reduced evolutionary potential in the face of rapid environmental change. To combat this augmentation of isolated populations with immigrants is sometimes used to facilitate demographic and genetic rescue. Augmentation with immigrants that are genetically and adaptively similar to the target population effectively increases population fitness, but if immigrants are very genetically or adaptively divergent, augmentation can lead to outbreeding depression. Despite well-cited guidelines for the best practice selection of immigrant sources, often only highly divergent populations remain, and experimental tests of these riskier augmentation scenarios are essentially nonexistent. We conducted a mesocosm experiment with Trinidadian guppies (Poecilia reticulata) to test the multigenerational demographic and genetic effects of augmenting 2 target populations with 3 types of divergent immigrants. We found no evidence of demographic rescue, but we did observe genetic rescue in one population. Divergent immigrant treatments tended to maintain greater genetic diversity, abundance, and hybrid fitness than controls that received immigrants from the source used to seed the mesocosms. In the second population, divergent immigrants had a slightly negative effect in one treatment, and the benefits of augmentation were less apparent overall, likely because this population started with higher genetic diversity and a lower reproductive rate that limited genetic admixture. Our results add to a growing consensus that gene flow can increase population fitness even when immigrants are more highly divergent and may help reduce uncertainty about the use of augmentation in conservation. © 2018 Society for Conservation Biology.
Directory of Open Access Journals (Sweden)
Burger Marieta
2011-02-01
Full Text Available Abstract Background One of the promising avenues for development of vaccines against Human immunodeficiency virus type 1 (HIV-1 and other human pathogens is the use of plasmid-based DNA vaccines. However, relatively large doses of plasmid must be injected for a relatively weak response. We investigated whether genome elements from Porcine circovirus type 1 (PCV-1, an apathogenic small ssDNA-containing virus, had useful expression-enhancing properties that could allow dose-sparing in a plasmid vaccine. Results The linearised PCV-1 genome inserted 5' of the CMV promoter in the well-characterised HIV-1 plasmid vaccine pTHgrttnC increased expression of the polyantigen up to 2-fold, and elicited 3-fold higher CTL responses in mice at 10-fold lower doses than unmodified pTHgrttnC. The PCV-1 capsid gene promoter (Pcap alone was equally effective. Enhancing activity was traced to a putative composite host transcription factor binding site and a "Conserved Late Element" transcription-enhancing sequence previously unidentified in circoviruses. Conclusions We identified a novel PCV-1 genome-derived enhancer sequence that significantly increased antigen expression from plasmids in in vitro assays, and improved immunogenicity in mice of the HIV-1 subtype C vaccine plasmid, pTHgrttnC. This should allow significant dose sparing of, or increased responses to, this and other plasmid-based vaccines. We also report investigations of the potential of other circovirus-derived sequences to be similarly used.
A microneedle patch containing measles vaccine is immunogenic in non-human primates.
Edens, Chris; Collins, Marcus L; Goodson, James L; Rota, Paul A; Prausnitz, Mark R
2015-09-08
Very high vaccination coverage is required to eliminate measles, but achieving high coverage can be constrained by the logistical challenges associated with subcutaneous injection. To simplify the logistics of vaccine delivery, a patch containing micron-scale polymeric needles was formulated to encapsulate the standard dose of measles vaccine (1000 TCID₅₀) and the immunogenicity of the microneedle patch was compared with subcutaneous injection in rhesus macaques. The microneedle patch was administered without reconstitution with diluent, dissolved in skin within 10 min, and caused only mild, transient skin erythema. Both groups of rhesus macaques generated neutralizing antibody responses to measles that were consistent with protection and the neutralizing antibody titers were equivalent. In addition, the microneedle patches maintained an acceptable level of potency after storage at elevated temperature suggesting improved thermostability compared to standard lyophilized vaccine. In conclusion, a measles microneedle patch vaccine was immunogenic in non-human primates, and this approach offers a promising delivery method that could help increase vaccination coverage. Copyright © 2015 Elsevier Ltd. All rights reserved.
Stadler, S.; Kain, K.; Giuliani, M.; Mirnig, N.; Stollnberger, G.; Tscheligi, M. ed
2016-01-01
Augmented reality (AR) can serve as a tool to provide helpful information in a direct way to industrial robot programmers throughout the teaching process. It seems obvious that AR support eases the programming process and increases the programmer's productivity and programming accuracy. However, additional information can also potentially increase the programmer's perceived workload. To explore the impact of augmented reality on robot teaching, as a first step we have chosen a Sphero robot co...
Cytokines in immunogenic cell death: Applications for cancer immunotherapy.
Showalter, Anne; Limaye, Arati; Oyer, Jeremiah L; Igarashi, Robert; Kittipatarin, Christina; Copik, Alicja J; Khaled, Annette R
2017-09-01
Despite advances in treatments like chemotherapy and radiotherapy, metastatic cancer remains a leading cause of death for cancer patients. While many chemotherapeutic agents can efficiently eliminate cancer cells, long-term protection against cancer is not achieved and many patients experience cancer recurrence. Mobilizing and stimulating the immune system against tumor cells is one of the most effective ways to protect against cancers that recur and/or metastasize. Activated tumor specific cytotoxic T lymphocytes (CTLs) can seek out and destroy metastatic tumor cells and reduce tumor lesions. Natural Killer (NK) cells are a front-line defense against drug-resistant tumors and can provide tumoricidal activity to enhance tumor immune surveillance. Cytokines like IFN-γ or TNF play a crucial role in creating an immunogenic microenvironment and therefore are key players in the fight against metastatic cancer. To this end, a group of anthracyclines or treatments like photodynamic therapy (PDT) exert their effects on cancer cells in a manner that activates the immune system. This process, known as immunogenic cell death (ICD), is characterized by the release of membrane-bound and soluble factors that boost the function of immune cells. This review will explore different types of ICD inducers, some in clinical trials, to demonstrate that optimizing the cytokine response brought about by treatments with ICD-inducing agents is central to promoting anti-cancer immunity that provides long-lasting protection against disease recurrence and metastasis. Copyright © 2017. Published by Elsevier Ltd.
Virulent poxviruses inhibit DNA sensing by preventing STING activation.
Georgana, Iliana; Sumner, Rebecca P; Towers, Greg J; Maluquer de Motes, Carlos
2018-02-28
Cytosolic recognition of DNA has emerged as a critical cellular mechanism of host immune activation upon pathogen invasion. The central cytosolic DNA sensor cGAS activates STING, which is phosphorylated, dimerises and translocates from the ER to a perinuclear region to mediate IRF-3 activation. Poxviruses are dsDNA viruses replicating in the cytosol and hence likely to trigger cytosolic DNA sensing. Here we investigated the activation of innate immune signalling by 4 different strains of the prototypic poxvirus vaccinia virus (VACV) in a cell line proficient in DNA sensing. Infection with the attenuated VACV strain MVA activated IRF-3 via cGAS and STING, and accordingly STING dimerised and was phosphorylated during MVA infection. Conversely, VACV strains Copenhagen and Western Reserve inhibited STING dimerisation and phosphorylation during infection and in response to transfected DNA and cGAMP, thus efficiently suppressing DNA sensing and IRF-3 activation. A VACV deletion mutant lacking protein C16, thought to be the only viral DNA sensing inhibitor acting upstream of STING, retained the ability to block STING activation. Similar inhibition of DNA-induced STING activation was also observed for cowpox and ectromelia viruses. Our data demonstrate that virulent poxviruses possess mechanisms for targeting DNA sensing at the level of the cGAS-STING axis and that these mechanisms do not operate in replication-defective strains such as MVA. These findings shed light on the role of cellular DNA sensing in poxvirus-host interactions and will open new avenues to determine its impact on VACV immunogenicity and virulence. IMPORTANCE Poxviruses are dsDNA viruses infecting a wide range of vertebrates and include the causative agent of smallpox (variola virus) and its vaccine vaccinia virus (VACV). Despite smallpox eradication VACV remains of interest as a therapeutic. Attenuated strains are popular vaccine candidates, whereas replication-competent strains are emerging as
Who’s That Girl? Handheld Augmented Reality for Printed Photo Books
Henze , Niels; Boll , Susanne
2011-01-01
Part 1: Long and Short Papers; International audience; Augmented reality on mobile phones has recently made major progress. Lightweight, markerless object recognition and tracking makes handheld Augmented Reality feasible for new application domains. As this field is technology driven the interface design has mostly been neglected. In this paper we investigate visualization techniques for augmenting printed documents using handheld Augmented Reality. We selected the augmentation of printed ph...
Chen, Huihui; Zhong, Fei; Li, Xiujin; Wang, Lu; Sun, Yan; Neng, Changai; Zhang, Kao; Li, Wenyan; Wen, Jiexia
2012-11-04
To investigate the effects of canine interleukin-2 (cIL-2) and cIL-7 genes on enhancing the immunogenicity of canine parvovirus (CPV) VP2 DNA vaccine. The bicistronic vectors of cIL-2 and cIL-7 genes were constructed using the eukaryotic expression vector containing internal ribosome entry site (IRES). The cIL-2/ cIL-7 dicistronic vector plus previously constructed vectors, including CPV VP2 DNA vaccine vector, cIL-2 vector and cIL-7 vector, were used to co-immunize mice with different combinations, consisting of VP2 alone, VP2 + cIL-2, VP2 + cIL-7 and VP2 + cIL-2/cIL-7. The VP2-specific antibody levels in immunized mice were measured by ELISA at different time post-immunization. The proliferation indices and interferon-gamma expression were measured by lymphocyte proliferation assay and ELISA, respectively. The cIL-2/cIL-7 bicistronic vector was correct and could mediate cIL-2 and cIL-7 gene expression in eukaryotic cells. Immunization results revealed that the antibody titers and the neutralizing antibody levels of the mice co-immunized with VP2 + cIL-7/cIL-2 vectors were significantly higher than that with either VP2 + cIL-2 vectors or VP2 + cIL-7 vectors (P vaccine.
Antiviral immunity in fish – functional analysis using DNA vaccination as a tool
DEFF Research Database (Denmark)
Lorenzen, Niels; Lorenzen, Ellen; Einer-Jensen, Katja
2013-01-01
fingerlings. Vaccination of fish at an early stage appears advantageous, since larger fish require higher doses of vaccine to be protected. Even in fish with an average size of 0.5 g at the time of vaccination, good protection can be obtained. Interestingly, immunity is established already a few days after...... and cellular components both play a role in the long lasting protection. The similarity of the functional immune response profile to that induced by a natural virus infection is striking and is most likely one of the major reasons for the efficacy of the rhabdovirus DNA vaccines. Although other elements like...... protein gene suggest that the structural requirements for antigenicity are different from the requirements for immunogenicity....
Towards an interactive medical system by augmented reality
Khawla Ben Abderrahim; Mohamed Kallel; M.S. Bouhlel
2013-01-01
Augmented reality is a computer field that progresses rapidly. Its principle is to mix the real world and the virtual world. Many applications already use augmented reality, particularly the medical field. Medical image allows doctors to make diagnosis of the patient. This diagnosis allows him to make the best decision without committing professional mistakes that can cause problems. Hence the idea of integrating augmented reality with medical image analysis to help the doctor to make the bes...
Jiskoot, Wim; Randolph, Theodore W; Volkin, David B; Middaugh, C Russell; Schöneich, Christian; Winter, Gerhard; Friess, Wolfgang; Crommelin, Daan J A; Carpenter, John F
2012-03-01
Protein instability and immunogenicity are two main roadblocks to the clinical success of novel protein drug delivery systems. In this commentary, we discuss the need for more extensive analytical characterization in relation to concerns about protein instability in injectable drug delivery systems for sustained release. We then will briefly address immunogenicity concerns and outline current best practices for using state-of-the-art analytical assays to monitor protein stability for both conventional and novel therapeutic protein dosage forms. Next, we provide a summary of the stresses on proteins arising during preparation of drug delivery systems and subsequent in vivo release. We note the challenges and difficulties in achieving the absolute requirement of quantitatively assessing the degradation of protein molecules in a drug delivery system. We describe the potential roles for academic research in further improving protein stability and developing new analytical technologies to detect protein degradation byproducts in novel drug delivery systems. Finally, we provide recommendations for the appropriate approaches to formulation design and assay development to ensure that stable, minimally immunogenic formulations of therapeutic proteins are created. These approaches should help to increase the probability that novel drug delivery systems for sustained protein release will become more readily available as effective therapeutic agents to treat and benefit patients. Copyright © 2011 Wiley Periodicals, Inc.
Singh, Deepti; Narayanamoorthy, Shwetha; Gamre, Sunita; Majumdar, Ananda Guha; Goswami, Manish; Gami, Umesh; Cherian, Susan; Subramanian, Mahesh
2018-05-20
Antibiotic resistance is a global problem and there is an urgent need to augment the arsenal against pathogenic bacteria. The emergence of different drug resistant bacteria is threatening human lives to be pushed towards the pre-antibiotic era. Botanical sources remain a vital source of diverse organic molecules that possess antibacterial property as well as augment existing antibacterial molecules. Piper betle, a climber, is widely used in south and south-east Asia whose leaves and nuts are consumed regularly. Hydroxychavicol (HC) isolated from Piper betle has been reported to possess antibacterial activity. It is currently not clear how the antibacterial activity of HC is manifested. In this investigation we show HC generates superoxide in E. coli cells. Antioxidants protected E. coli against HC induced cell death while gshA mutant was more sensitive to HC than wild type. DNA damage repair deficient mutants are hypersensitive to HC and HC induces the expression of DNA damage repair genes that repair oxidative DNA damage. HC treated E. coli cells are inhibited from growth and undergo DNA condensation. In vitro HC binds to DNA and cleaves it in presence of copper. Our data strongly indicates HC mediates bacterial cell death by ROS generation and DNA damage. Damage to iron sulfur proteins in the cells contribute to amplification of oxidative stress initiated by HC. Further HC is active against a number of Gram negative bacteria isolated from patients with a wide range of clinical symptoms and varied antibiotic resistance profiles. Copyright © 2018 Elsevier Inc. All rights reserved.
Li, Rong-cheng; Li, Feng-xiang; Li, Yan-ping
2009-06-01
To evaluate the safety and immunogenicity of the booster dose of 7 valent pneumococcal conjugate vaccine (PCV7) to the healthy Chinese toddlers who had received 3 primary doses. Four hundred and eighty-eight Chinese toddlers received a booster dose of PCV7 at age of 12-15 months following a primary series of the vaccine given at ages 3, 4, 5 months separately with Diphtheria Tetanus Acellular Pertussis Combined Vaccine (DTaP) in Group 1 or concurrently with DTaP in Group 2. Following the booster dose immunization, each subject was followed up for 30 days to observe the safety of the vaccine. Blood samples were taken from a subset of subjects prior and post 30 days the booster dose immunization to evaluate immunogenicity. A high proportion of subjects in Group 1 (89%) and Group 2 (91%) remained afebrile after the booster dose. Local reactions to the PCV7 booster dose were generally mild. For each serotype, the rise in GMC (post-/pre-vaccination) showed a statistically significant difference (P<0.0001) between both groups. PCV7 administered as a booster dose is generally safe, well tolerate, and immunogenic in healthy Chinese toddlers.
Identification and characterization of immunogenic proteins of Mycoplasma genitalium
DEFF Research Database (Denmark)
Svenstrup, Helle Friis; Jensen, J.S.; Gevaert, K.
2006-01-01
serum against M. genitalium G37, determine their identity by mass spectrometry, and develop an M. genitalium-specific enzyme-linked immunosorbent assay (ELISA) free from cross-reactivity with M. pneumoniae antibodies. Using recombinant fragments of the C-terminal part of MgPa (rMgPa), we developed....... genitalium strains were isolated (J. S. Jensen, H. T. Hansen, and K. Lind, J. Clin. Microbiol. 34:286-291, 1996). The objective of this study was to characterize immunogenic proteins of M. genitalium by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting by using a hyperimmune rabbit...
Directory of Open Access Journals (Sweden)
Merika T Koday
Full Text Available Recent avian and swine-origin influenza virus outbreaks illustrate the ongoing threat of influenza pandemics. We investigated immunogenicity and protective efficacy of a multi-antigen (MA universal influenza DNA vaccine consisting of HA, M2, and NP antigens in cynomolgus macaques. Following challenge with a heterologous pandemic H1N1 strain, vaccinated animals exhibited significantly lower viral loads and more rapid viral clearance when compared to unvaccinated controls. The MA DNA vaccine induced robust serum and mucosal antibody responses but these high antibody titers were not broadly neutralizing. In contrast, the vaccine induced broadly-reactive NP specific T cell responses that cross-reacted with the challenge virus and inversely correlated with lower viral loads and inflammation. These results demonstrate that a MA DNA vaccine that induces strong cross-reactive T cell responses can, independent of neutralizing antibody, mediate significant cross-protection in a nonhuman primate model and further supports development as an effective approach to induce broad protection against circulating and emerging influenza strains.
DNA priming for seasonal influenza vaccine: a phase 1b double-blind randomized clinical trial.
Directory of Open Access Journals (Sweden)
Julie E Ledgerwood
Full Text Available The efficacy of current influenza vaccines is limited in vulnerable populations. DNA vaccines can be produced rapidly, and may offer a potential strategy to improve vaccine immunogenicity, indicated by studies with H5 influenza DNA vaccine prime followed by inactivated vaccine boost.Four sites enrolled healthy adults, randomized to receive 2011/12 seasonal influenza DNA vaccine prime (n=65 or phosphate buffered saline (PBS (n=66 administered intramuscularly with Biojector. All subjects received the 2012/13 seasonal inactivated influenza vaccine, trivalent (IIV3 36 weeks after the priming injection. Vaccine safety and tolerability was the primary objective and measurement of antibody response by hemagglutination inhibition (HAI was the secondary objective.The DNA vaccine prime-IIV3 boost regimen was safe and well tolerated. Significant differences in HAI responses between the DNA vaccine prime and the PBS prime groups were not detected in this study.While DNA priming significantly improved the response to a conventional monovalent H5 vaccine in a previous study, it was not effective in adults using seasonal influenza strains, possibly due to pre-existing immunity to the prime, unmatched prime and boost antigens, or the lengthy 36 week boost interval. Careful optimization of the DNA prime-IIV3 boost regimen as related to antigen matching, interval between vaccinations, and pre-existing immune responses to influenza is likely to be needed in further evaluations of this vaccine strategy. In particular, testing this concept in younger age groups with less prior exposure to seasonal influenza strains may be informative.ClinicalTrials.gov NCT01498718.
Maspi, Nahid; Ghaffarifar, Fatemeh; Sharifi, Zohreh; Dalimi, Abdolhossein; Dayer, Mohammad Saaid
2017-03-01
There is no effective vaccine for the prevention and elimination of leishmaniasis. For this reason, we assessed the protective effects of DNA vaccines containing LeIF, TSA genes alone, or LeIF-TSA fusion against cutaneous leishmaniasis pEGFP-N1 plasmid (empty vector) and phosphate buffer saline (PBS) were used as control groups. Therefore, cellular and humoral immune responses were evaluated before and after the challenge with Leishmania major. Lesion diameter was also measured 3-12 weeks after challenge. All immunized mice with plasmid DNA encoding Leishmania antigens induced the partial immunity characterized by increased IFN-γ and IgG2a levels compared with control groups (p TSA, and LeIF-TSA, respectively, than in PBS group at 12th week post infection. IFN/IL-4 and IgG2a/IgG1 ratios indicated that group receiving LeIF-TSA fusion had the highest IFN-γ and IgG2a levels. In this study, DNA immunization promoted Th1 immune response characterized by higher IFN-γ and IgG2a levels and also reduction in lesion size. These results showed that a bivalent vaccine containing two distinct antigens may induce more potent immune responses against leishmaniasis. © 2017 APMIS. Published by John Wiley & Sons Ltd.
DNA capture reveals transoceanic gene flow in endangered river sharks
Li, Chenhong; Corrigan, Shannon; Yang, Lei; Straube, Nicolas; Harris, Mark; Hofreiter, Michael; White, William T.; Naylor, Gavin J. P.
2015-01-01
The river sharks of the genus Glyphis, widely feared as man-eaters throughout India, remain very poorly known to science. The group constitutes five described species, all of which are considered highly endangered and restricted to freshwater systems in Australasia and Southeast Asia. DNA sequence data derived from 19th-century dried museum material augmented with contemporary samples indicates that only three of the five currently described species are valid; that there is a genetically dist...
[Display technologies for augmented reality in medical applications].
Eck, Ulrich; Winkler, Alexander
2018-04-01
One of the main challenges for modern surgery is the effective use of the many available imaging modalities and diagnostic methods. Augmented reality systems can be used in the future to blend patient and planning information into the view of surgeons, which can improve the efficiency and safety of interventions. In this article we present five visualization methods to integrate augmented reality displays into medical procedures and the advantages and disadvantages are explained. Based on an extensive literature review the various existing approaches for integration of augmented reality displays into medical procedures are divided into five categories and the most important research results for each approach are presented. A large number of mixed and augmented reality solutions for medical interventions have been developed as research prototypes; however, only very few systems have been tested on patients. In order to integrate mixed and augmented reality displays into medical practice, highly specialized solutions need to be developed. Such systems must comply with the requirements with respect to accuracy, fidelity, ergonomics and seamless integration into the surgical workflow.
Ángela María Ruiz-Sternberg; Edson D. Moreira, Jr; Jaime A. Restrepo; Eduardo Lazcano-Ponce; Robinson Cabello; Arnaldo Silva; Rosires Andrade; Francisco Revollo; Santos Uscanga; Alejandro Victoria; Ana María Guevara; Joaquín Luna; Manuel Plata; Claudia Nossa Dominguez; Edison Fedrizzi
2018-01-01
Background: A 9-valent human papillomavirus (HPV6/11/16/18/31/33/45/52/58; 9vHPV) vaccine was developed to expand coverage of the previously developed quadrivalent (HPV6/11/16/18; qHPV) vaccine. Methods: Efficacy, immunogenicity, and safety outcomes were assessed in Latin American participants enrolled in 2 international studies of the 9vHPV vaccine, including a randomized, double-blinded, controlled with qHPV vaccine, efficacy, immunogenicity, and safety study in young women aged 16–26 years...
Elsayid, Mohieldin; Al Qahtani, Faris Saeed; Al Qarni, Abdulaziz Mohammed; Almajed, Faisal; Al Saqri, Faisal; Qureshi, Shoeb
2017-01-01
Background: The Rhesus (Rh) blood group system is one of the most polymorphic and immunogenic systems known in humans, because of its immunogenicity along with ABO grouping, RhD antigen testing was made mandatory before issuing a compatible blood. At present, there are five major antigens, i.e., D, C, E, c, and e in Rh blood group system. Aims: The aim of this study is to provide essential data about the distribution of the major Rh antigens and the most common phenotype among the Saudi popul...
Calarota, Sandra A; Weiner, David B
2004-06-01
It is clear that the development of a safe and effective vaccine for human immunodeficiency virus type 1 (HIV-1) remains a crucial goal for controlling the acquired immunodeficiency syndrome epidemic. At present, it is not clear what arm of the immune response correlates with protection from HIV-1 infection or disease. Therefore, a strong cellular and humoral immune response will likely be needed to control this infection. Among different vaccine alternatives, DNA vaccines appeared more than a decade ago, demonstrating important qualities of inducing both humoral and cellular immune responses in animal models. However, after several years and various clinical studies in humans, supporting the safety of the HIV-DNA vaccine strategies, it has become clear that their potency should be improved. One way to modulate and enhance the immune responses induced by a DNA vaccine is by including genetic adjuvants such as cytokines, chemokines, or T-cell costimulatory molecules as part of the vaccine itself. Particularly, vaccine immunogenicity can be modulated by factors that attract professional antigen-presenting cells, provide additional costimulation, or enhance the uptake of plasmid DNA. This review focuses on developments in the coadministration of molecular adjuvants for the enhancement of HIV-1 DNA-vaccine potency.
Directory of Open Access Journals (Sweden)
Henrik N Kløverpris
Full Text Available HIV Gag-specific CD4+ and CD8+ T-cell responses are important for HIV immune control. Pulsing overlapping Gag peptides on autologous lymphocytes (OPAL has proven immunogenic and effective in reducing viral loads in multiple pigtail macaque studies, warranting clinical evaluation.We performed a phase I, single centre, placebo-controlled, double-blinded and dose-escalating study to evaluate the safety and preliminary immunogenicity of a novel therapeutic vaccine approach 'OPAL-HIV-Gag(c'. This vaccine is comprised of 120 15mer peptides, overlapping by 11 amino acids, spanning the HIV Gag C clade sequence proteome, pulsed on white blood cells enriched from whole blood using a closed system, followed by intravenous reinfusion. Patients with undetectable HIV viral loads (<50 copies/ml plasma on HAART received four administrations at week 0, 4, 8 and 12, and were followed up for 12 weeks post-treatment. Twenty-three people were enrolled in four groups: 12 mg (n = 6, 24 mg (n = 7, 48 mg (n = 2 or matching placebo (n = 8 with 18 immunologically evaluable. T-cell immunogenicity was assessed by IFNγ ELIspot and intracellular cytokine staining (ICS.The OPAL-HIV-Gag(c peptides were antigenic in vitro in 17/17 subjects. After vaccination with OPAL-HIV-Gag(c, 1/6 subjects at 12 mg and 1/6 subjects at 24 mg dose groups had a 2- and 3-fold increase in ELIspot magnitudes from baseline, respectively, of Gag-specific CD8+ T-cells at week 14, compared to 0/6 subjects in the placebo group. No Gag-specific CD4+ T-cell responses or overall change in Rev, Nef, Tat and CMV specific responses were detected. Marked, transient and self-limiting lymphopenia was observed immediately post-vaccination (4 hours in OPAL-HIV-Gag(c but not in placebo recipients, with median fall from 1.72 to 0.67 million lymphocytes/mL for active groups (P<0.001, compared to post-placebo from 1.70 to 1.56 lymphocytes/ml (P = 0.16.Despite strong immunogenicity observed in
Ionizing radiation enhances immunogenicity of cells expressing a tumor-specific T-cell epitope
International Nuclear Information System (INIS)
Ciernik, Ilja F.; Romero, Pedro; Berzofsky, Jay A.; Carbone, David P.
1999-01-01
Background: p53 point mutations represent potential tumor-specific cytolytic T lymphocyte (CTL) epitopes. Whether ionizing radiation (IR) alters the immunological properties of cells expressing mutant p53 in respect of the CTL epitope generated by a defined point mutation has not been evaluated. Methods: Mutant p53-expressing syngeneic, nontumor forming BALB/c 3T3 fibroblasts, tumor forming ras-transfected BALB/c 3T3 sarcomas, and DBA/2-derived P815 mastocytoma cells, which differ at the level of minor histocompatibility antigens, were used as cellular vaccines. Cells were either injected with or without prior IR into naive BALB/c mice. Cellular cytotoxicity was assessed after secondary restimulation of effector spleen cells in vitro. Results: Injection of P815 mastocytoma cells expressing the mutant p53 induced mutation-specific CTL in BALB/c mice irrespective of prior irradiation. However, syngeneic fibroblasts or fibrosarcomas endogenously expressing mutant p53 were able to induce significant mutation-specific CTL only when irradiated prior to injection into BALB/c mice. IR of fibroblasts did not detectably alter the expression of cell surface molecules involved in immune response induction, nor did it alter the short-term in vitro viability of the fibroblasts. Interestingly, radioactively-labeled fibroblasts injected into mice after irradiation showed altered organ distribution, suggesting that the in vivo fate of these cells may play a crucial role in their immunogenicity. Conclusions: These findings indicate that IR can alter the immunogenicity of syngeneic normal as well as tumor forming fibroblasts in vivo, and support the view that ionizing radiation enhances immunogenicity of cellular tumor vaccines
Determination of student opinions in augmented reality
Directory of Open Access Journals (Sweden)
Huseyin Bicen
2016-11-01
Full Text Available The rapid development of the new technology has changed classroom teaching methods and tools in a positive way. This study investigated the classroom learning with augmented reality and the impact of student opinions. 97 volunteer undergraduate students took part in this study. Results included data in the form of frequencies, percentages and descriptive statistics. The results show that, with gamification methods, augmented reality content affected students’ opinions in a positive way. When QR codes are used in the classroom, students feel independent from classroom materials and can access various resources. Moreover, students think that, when augmented reality in the classroom is used, education is more enjoyable.
Normative Data for Interpreting the BREAST-Q: Augmentation
Mundy, Lily R.; Homa, Karen; Klassen, Anne F.; Pusic, Andrea L.; Kerrigan, Carolyn L.
2016-01-01
Background The BREAST-Q is a rigorously developed, well-validated, patient-reported outcome (PRO) instrument with a module designed for evaluating breast augmentation outcomes. However, there are no published normative BREAST-Q scores, limiting interpretation. Methods Normative data were generated for the BREAST-Q Augmentation Module via the Army of Women (AOW), an online community of women (with and without breast cancer) engaged in breast-cancer related research. Members were recruited via email, with women 18 years or older without a history of breast cancer or breast surgery invited to participate. Descriptive statistics and a linear multivariate regression were performed. A separate analysis compared normative scores to findings from previously published BREAST-Q augmentation studies. Results The preoperative BREAST-Q Augmentation Module was completed by 1,211 women. Mean age was 54 ±24 years, mean body mass index (BMI) was 27 ±6, and 39% (n=467) had a bra cup size ≥D. Mean scores were Satisfaction with Breasts (54 ±19), Psychosocial Well-being (66 ±20), Sexual Well-being (49 ±20), and Physical Well-being (86 ±15). Women with a BMI of 30 or greater and bra cup size D or greater had lower scores. In comparison to AOW scores, published BREAST-Q augmentation scores were lower before and higher after surgery for all scales except Physical Well-being. Conclusions The AOW normative data represent breast-related satisfaction and well-being in woman not actively seeking breast augmentation. This data may be used as normative comparison values for those seeking and undergoing surgery as we did, demonstrating the value of breast augmentation in this patient population. PMID:28350657
Teodorowicz, Malgorzata; van Neerven, Joost
2017-01-01
The majority of foods that are consumed in our developed society have been processed. Processing promotes a non-enzymatic reaction between proteins and sugars, the Maillard reaction (MR). Maillard reaction products (MRPs) contribute to the taste, smell and color of many food products, and thus influence consumers’ choices. However, in recent years, MRPs have been linked to the increasing prevalence of diet- and inflammation-related non-communicable diseases including food allergy. Although during the last years a better understanding of immunogenicity of MRPs has been achieved, still only little is known about the structural/chemical characteristics predisposing MRPs to interact with antigen presenting cells (APCs). This report provides a comprehensive review of recent studies on the influence of the Maillard reaction on the immunogenicity and allergenicity of food proteins. PMID:28777346
Teodorowicz, Malgorzata; van Neerven, Joost; Savelkoul, Huub
2017-08-04
The majority of foods that are consumed in our developed society have been processed. Processing promotes a non-enzymatic reaction between proteins and sugars, the Maillard reaction (MR). Maillard reaction products (MRPs) contribute to the taste, smell and color of many food products, and thus influence consumers' choices. However, in recent years, MRPs have been linked to the increasing prevalence of diet- and inflammation-related non-communicable diseases including food allergy. Although during the last years a better understanding of immunogenicity of MRPs has been achieved, still only little is known about the structural/chemical characteristics predisposing MRPs to interact with antigen presenting cells (APCs). This report provides a comprehensive review of recent studies on the influence of the Maillard reaction on the immunogenicity and allergenicity of food proteins.
[Association between oxytocin augmentation intervals and the risk of postpartum haemorrhage].
Loscul, C; Chantry, A-A; Caubit, L; Deneux-Tharaux, C; Goffinet, F; Le Ray, C
2016-09-01
To study the association between the duration of oxytocin augmentation intervals and the risk of postpartum haemorrhage (PPH) among primiparous women in spontaneous labour. Retrospective cohort including primiparous women in spontaneous labour who received oxytocin during labour (n=454). Oxytocin augmentation intervals were dichotomized in intervalsoxytocin augmentation intervals. The association between oxytocin augmentation intervals and PPH was analyzed using univariate and multivariate analysis. Oxytocin augmentation intervals were shorter than 20minutes for 43.8% of the study population. The rate of PPH was higher (9.1% vs 3.5%; P=0.014), and the use of sulprostone was more frequent (6.5% vs 3.5%; P=0.013) if oxytocin augmentation intervals were shorter than 20minutes in comparison with intervals≥20minutes. The association between oxytocin augmentation intervals and PPH remains significant after adjustment on other PPH risk factors (adjusted OR=3.48, 95% CI [1.45-8.34]). The rate of adverse neonatal issue, defined by arterial pH at birth≤7.10 and/or 5minutes score d'Apgar≤7, was higher if oxytocin augmentation intervals wereoxytocin with augmentation intervals shorter than 20minutes. Copyright © 2016. Published by Elsevier Masson SAS.
Spatial augmented reality merging real and virtual worlds
Bimber, Oliver
2005-01-01
Like virtual reality, augmented reality is becoming an emerging platform in new application areas for museums, edutainment, home entertainment, research, industry, and the art communities using novel approaches which have taken augmented reality beyond traditional eye-worn or hand-held displays. In this book, the authors discuss spatial augmented reality approaches that exploit optical elements, video projectors, holograms, radio frequency tags, and tracking technology, as well as interactive rendering algorithms and calibration techniques in order to embed synthetic supplements into the real
Immunogenic Targets for Specific Immunotherapy in Multiple Myeloma
Directory of Open Access Journals (Sweden)
Lu Zhang
2012-01-01
Full Text Available Multiple myeloma remains an incurable disease although the prognosis has been improved by novel therapeutics and agents recently. Relapse occurs in the majority of patients and becomes fatal finally. Immunotherapy might be a powerful intervention to maintain a long-lasting control of minimal residual disease or to even eradicate disseminated tumor cells. Several tumor-associated antigens have been identified in patients with multiple myeloma. These antigens are expressed in a tumor-specific or tumor-restricted pattern, are able to elicit immune response, and thus could serve as targets for immunotherapy. This review discusses immunogenic antigens with therapeutic potential for multiple myeloma.
APC targeting enhances immunogenicity of a novel multistage Fc-fusion tuberculosis vaccine in mice.
Soleimanpour, Saman; Farsiani, Hadi; Mosavat, Arman; Ghazvini, Kiarash; Eydgahi, Mohammad Reza Akbari; Sankian, Mojtaba; Sadeghian, Hamid; Meshkat, Zahra; Rezaee, Seyed Abdolrahim
2015-12-01
Numerous studies have demonstrated that targeting immunogens to FcγR on antigen-presenting cells (APCs) can selectively uptake and increase cellular immunity in vitro and in vivo. Therefore, the present study was conducted to evaluate immunogenicity of a novel multistage tuberculosis vaccine, a combination of an early and a dormant immunogenic protein, ESAT6 and HspX, fused to Fcγ2a fragment of mouse IgG2a to target all forms of tuberculosis. Codon-optimized genes consisting of ESAT6, a linker, and HspX fused either to mouse Fcγ2a (ESAT6:HspX:mFcγ2a) or 6× His-tag (ESAT6:HspX:His) were synthesized. The resulting proteins were then produced in Pichia pastoris. The fusion proteins were separately emulsified in dimethyldioctadecylammonium bromide(DDA)-trehalose-6,6-dibehenate(TDB) adjuvant, and their immunogenicity with and without bacille Calmette-Guérin (BCG) was assessed in C57BL/6 mice. Th1, Th2, Th17, and T-reg cytokine patterns were evaluated using the ELISA method. Both multistage vaccines induced very strong IL-12 and IFN-γ secretion from splenic cells; the Fc-tagged subunit vaccine induced a more effective Th1 immune response (IFN-γ, 910 pg/mL, and IL-12, 854 pg/mL) with a very low increase in IL-17 (∼0.1 pg/mL) and IL-4 (37 pg/mL) and a mild increase in TGF-β (543 pg/mL) compared to the BCG or ESAT6:HspX:His primed and boosted groups. The production of IFN-γ to ESAT6:HspX:Fcγ2a was very consistent and showed an increasing trend for IL-12 compared to the BCG or ESAT6:HspX:His primed and boosted groups. Fcγ2a used as a delivery vehicle supported the idea of selective uptake, inducing cross-presentation and forming a proper anti-tuberculosis response in context of Th1/Th2 and Th17/T-reg balances, which is important for protection and prevention of damage.
Facial skeletal augmentation using hydroxyapatite cement.
Shindo, M L; Costantino, P D; Friedman, C D; Chow, L C
1993-02-01
This study investigates the use of a new calcium phosphate cement, which sets to solid, microporous hydroxyapatite, for facial bone augmentation. In six dogs, the supraorbital ridges were augmented bilaterally with this hydroxyapatite cement. On one side, the hydroxyapatite cement was placed directly onto the bone within a subperiosteal pocket. On the opposite side, the cement was contained within a collagen membrane tubule and then inserted into a subperiosteal pocket. The use of collagen tubules facilitated easy, precise placement of the cement. All implants maintained their original augmented height throughout the duration of the study. They were well tolerated without extrusion or migration, and there was no significant sustained inflammatory response. Histologic studies, performed at 3, 6, and 9 months revealed that when the cement was placed directly onto bone, progressive replacement of the implant by bone (osseointegration of the hydroxyapatite with the underlying bone) without a loss of volume was observed. In contrast, when the cement-collagen tubule combination was inserted, primarily a fibrous union was noted. Despite such fibrous union, the hydroxyapatite-collagen implant solidly bonded to the underlying bone, and no implant resorption was observed. Hydroxyapatite cement can be used successfully for the experimental augmentation of the craniofacial skeleton and may be applicable for such uses in humans.
Inhibition of DNA binding of Sox2 by the SUMO conjugation
International Nuclear Information System (INIS)
Tsuruzoe, Shu; Ishihara, Ko; Uchimura, Yasuhiro; Watanabe, Sugiko; Sekita, Yoko; Aoto, Takahiro; Saitoh, Hisato; Yuasa, Yasuhito; Niwa, Hitoshi; Kawasuji, Michio; Baba, Hideo; Nakao, Mitsuyoshi
2006-01-01
Sox2 is a member of the high mobility group (HMG) domain DNA-binding proteins for transcriptional control and chromatin architecture. The HMG domain of Sox2 binds the DNA to facilitate transactivation by the cooperative transcription factors such as Oct3/4. We report that mouse Sox2 is modified by SUMO at lysine 247. Substitution of the target lysine to arginine lost the sumoylation but little affected transcriptional potential or nuclear localization of Sox2. By contrast with the unmodified form, Sox2 fused to SUMO-1 did not augment transcription via the Fgf4 enhancer in the presence of Oct3/4. Further, SUMO-1-conjugated Sox2 at the lysine 247 or at the carboxyl terminus reduced the binding to the Fgf4 enhancer. These indicate that Sox2 sumoylation negatively regulates its transcriptional role through impairing the DNA binding
Novel Augmentation Strategies in Major Depression
DEFF Research Database (Denmark)
Martiny, Klaus
2017-01-01
open psychiatric wards. Only a few patients were re-cruited through advertisements (in the PEMF and Chronos studies). Inclusion criteria Inclusion criteria were major depression according to the DSM-IV, including a depressive episode as part of a bipolar disorder. For the PEMF study, treatment...... The results from the Pindolol study showed that pindolol did not augment the effect of venlafaxine for the whole sample. However, for those patients classified as slow metabolizers, based on their O-desmethylvenlafaxine/venlafaxine ratio (ODV/V), pindolol did augment the antidepressant effect. For patients...... classified as fast metabolizers, pindolol worsened the outcome. This interaction between ODV/V ratio and treatment group was statistically significant (p = 0.01). Results from the PEMF study The results from the PEMF Study showed that treatment with active versus sham PEMF augmented the effect of the ongoing...
Aarden, Lucien; Ruuls, Sigrid R; Wolbink, Gertjan
2008-08-01
To date, millions of people have been treated with therapeutic monoclonal antibodies (TmAbs) for various indications. It is becoming increasingly clear that TmAbs can be immunogenic, which may reduce efficacy or induce adverse effects. Over the years, the importance of antibody formation has been questioned and sometimes minimized, as few antibody responses to TmAbs (HACA or HAHA) were reported. However, the methods to detect and quantify such antibodies used in the past have been problematic. Only recently, methods have been developed that have adequate sensitivity and are not seriously disturbed by false-positive reactions caused by rheumatoid factors, natural antibodies to Fab or F(ab')2 fragments, or Fc interactions of IgG4. The large number of treated patients, in combination with these new assays, presents a unique opportunity to study the anti-antibody immune response in man, possibly allowing us to manipulate immunogenicity in the future.
Directory of Open Access Journals (Sweden)
Abdul Rouf Mir
Full Text Available Increased oxidative stress under hyperglycemic conditions, through the interaction of AGEs with RAGE receptors and via activation of interleukin mediated transcription signalling, has been reported in cancer. Proteins modifications are being explored for their roles in the development and progression of cancer and autoantibody response against them is gaining interest as a probe for early detection of the disease. This study has analysed the changes in histone H1 upon modification by methylglyoxal (MG and its implications in auto-immunopathogenesis of cancer. Modified histone showed modifications in the aromatic residues, changed tyrosine microenvironment, intermolecular cross linking and generation of AGEs. It showed masking of hydrophobic patches and a hypsochromic shift in the in ANS specific fluorescence. MG aggressively oxidized histone H1 leading to the accumulation of reactive carbonyls. Far UV CD measurements showed di-carbonyl induced enhancement of the alpha structure and the induction of beta sheet conformation; and thermal denaturation (Tm studies confirmed the thermal stability of the modified histone. FTIR analysis showed amide I band shift, generation of a carboxyethyl group and N-Cα vibrations in the modified histone. LCMS analysis confirmed the formation of Nε-(carboxyethyllysine and electron microscopic studies revealed the amorphous aggregate formation. The modified histone showed altered cooperative binding with DNA. Modified H1 induced high titre antibodies in rabbits and the IgG isolated form sera of rabbits immunized with modified H1 exhibited specific binding with its immunogen in Western Blot analysis. IgG isolated from the sera of patients with lung cancer, prostate cancer, breast cancer and cancer of head and neck region showed better recognition for neo-epitopes on the modified histone, reflecting the presence of circulating autoantibodies in cancer. Since reports suggest a link between AGE-RAGE axis and
Directory of Open Access Journals (Sweden)
Inés Martín-Martín
2013-01-01
Full Text Available Sand fly salivary proteins are on the spotlight to become vaccine candidates against leishmaniasis and to markers of exposure to sand fly bites due to the host immune responses they elicit. Working with the whole salivary homogenate entails serious drawbacks such as the need for maintaining sand fly colonies and the laborious task of glands dissection. In order to overcome these difficulties, producing recombinant proteins of different vectors has become a major task. In this study, a cDNA library was constructed with the salivary glands of Phlebotomus perniciosus from Madrid, Spain, the most widespread vector of Leishmania infantum in the Mediterranean basin. Analysis of the cDNA sequences showed several polymorphisms among the previously described salivary transcripts. The apyrase SP01B and the D7-related protein SP04 were successfully cloned, expressed in Escherichia coli, and purified. Besides, recombinant proteins were recognized by sera of hamsters and mice previously immunized with saliva through the exposure to uninfected sand fly bites. These results suggest that these two recombinant proteins conserved their immunogenic properties after expression in a prokaryote system. Therefore, this work contributes to expand the knowledge of P. perniciosus saliva that would be eventually used for the development of tools for vector control programs.
Safety and immunogenicity of a live attenuated mumps vaccine: a phase I clinical trial.
Liang, Yan; Ma, Jingchen; Li, Changgui; Chen, Yuguo; Liu, Longding; Liao, Yun; Zhang, Ying; Jiang, Li; Wang, Xuan-Yi; Che, Yanchun; Deng, Wei; Li, Hong; Cui, Xiaoyu; Ma, Na; Ding, Dong; Xie, Zhongping; Cui, Pingfang; Ji, Qiuyan; Wang, JingJing; Zhao, Yuliang; Wang, Junzhi; Li, Qihan
2014-01-01
Mumps, a communicable, acute and previously well-controlled disease, has had recent and occasional resurgences in some areas. A randomized, double-blind, controlled and multistep phase I study of an F-genotype attenuated mumps vaccine produced in human diploid cells was conducted. A total of 300 subjects were enrolled and divided into 4 age groups: 16-60 years, 5-16 years, 2-5 years and 8-24 months. The groups were immunized with one injection per subject. Three different doses of the F-genotype attenuated mumps vaccine, A (3.5 ± 0.25 logCCID50), B (4.25 ± 0.25 logCCID50) and C (5.0 ± 0.25 logCCID50), as well as a placebo control and a positive control of a licensed A-genotype vaccine (S79 strain) were used. The safety and immunogenicity of this vaccine were compared with those of the controls. The safety evaluation suggested that mild adverse reactions were observed in all groups. No serious adverse event (SAE) was reported throughout the trial. The immunogenicity test showed a similar seroconversion rate of the neutralizing and ELISA antibody in the 2- to 5-year-old and 8- to 24-month-old groups compared with the seroconversion rate in the positive control. The GMT of the neutralizing anti-F-genotype virus antibodies in the vaccine groups was slightly higher than that in the positive control group. The F-genotype attenuated mumps vaccine evaluated in this clinical trial was demonstrated to be safe and have effective immunogenicity vs. control.
Applying Augmented Reality in practical classes for engineering students
Bazarov, S. E.; Kholodilin, I. Yu; Nesterov, A. S.; Sokhina, A. V.
2017-10-01
In this article the Augmented Reality application for teaching engineering students of electrical and technological specialties is introduced. In order to increase the motivation for learning and the independence of students, new practical guidelines on Augmented Reality were developed in the application to practical classes. During the application development, the authors used software such as Unity 3D and Vuforia. The Augmented Reality content consists of 3D-models, images and animations, which are superimposed on real objects, helping students to study specific tasks. A user who has a smartphone, a tablet PC, or Augmented Reality glasses can visualize on-screen virtual objects added to a real environment. Having analyzed the current situation in higher education: the learner’s interest in studying, their satisfaction with the educational process, and the impact of the Augmented Reality application on students, a questionnaire was developed and offered to students; the study involved 24 learners.
DEFF Research Database (Denmark)
Mikkelsen, Heidi; Tollefsen, S.; Olsen, I.
Paratuberculosis in ruminants is caused by an infection with Mycobacterium avium subspecies paratuberculosis (MAP) and is a chronic disease characterized by granulomatous enteritis. Available vaccines against paratuberculosis consist of variations of whole bacteria with adjuvant showing various...... efficacies. The main problem with available vaccines is their interference with surveillance and diagnosis of bovine tuberculosis and paratuberculosis. Our ultimate aim is to develop a subunit vaccine consisting of selected MAP peptides, which allow differentiation of infected from vaccinated animals. Here......, 118 peptides were identified by in silico analysis and synthesized chemically. Peptides were tested for reactivity and immunogenicity with T-cell lines generated from PBMCs isolated from MAP infected goats and with blood samples from MAP infected calves. Immunogenicity of peptides was evaluated using...
Lomakin, Ya A; Shmidt, A A; Bobik, T V; Chernov, A S; Pyrkov, A Yu; Aleksandrova, N M; Okunola, D O; Vaskina, M I; Ponomarenko, N A; Telegin, G B; Dubina, M V; Belogurov, A A
2017-10-01
Intracellular fragments of latent phase protein LMP1 of Epstein-Barr virus, denoted as CTAR1/2/3, can trigger a variety of cell cascades and contribute to the transforming potential of the virus. Generation of recombinant proteins CTAR1/2/3 is expected to yield more ample data on functional and immunogenic characteristics of LMP1. We created genetic constructs for prokaryotic expression of LMP1 CTAR fragments and selected optimal conditions for their production and purification. Using a new library of LMP1 CTAR fragments, we carried out epitope mapping of a diagnostic anti-LMP1 antibody S12. Analysis of polyclonal serum antibodies from mice immunized with full-length LMP1 confirmed immunogenicity of CTAR elements comparable with that of full-length protein.
Safety and Immunogenicity of a Candidate Parvovirus B19 Vaccine
Bernstein, David I; El Sahly, Hana M; Keitel, Wendy A; Wolff, Mark; Simone, Gina; Segawa, Claire; Wong, Susan; Shelly, Daniel; Young, Neal S; Dempsey, Walla
2011-01-01
Parvovirus B19 is an important human pathogen causing erythema infectiosum, transient aplastic crisis in individuals with underlying hemolytic disorders and hydrops fetalis. We therefore evaluated a parvovirus B19 virus like particle (VLP) vaccine. The safety and immunogenicity of a 25 μg dose of parvovirus B19 recombinant capsid; 2.5 and 25 μg doses of the recombinant capsid given with MF59; and saline placebo were assessed in healthy adults. Because of 3 unexplained cutaneous events the stu...
Sensor-augmented pump therapy at 36 months
DEFF Research Database (Denmark)
Schmidt, Signe; Nørgaard, Kirsten
2012-01-01
This follow-up study investigates the metabolic and psychosocial effects of sensor-augmented pump (SAP) therapy in adults with type 1 diabetes 36 months after therapy start.......This follow-up study investigates the metabolic and psychosocial effects of sensor-augmented pump (SAP) therapy in adults with type 1 diabetes 36 months after therapy start....
National Aeronautics and Space Administration — Augmented Reality systems come with many benefits derived by co-locating information with a user's environment through the use of one or more output modalities such...
Cosmetic tourism for breast augmentation: a systematic review.
Brightman, Louise; Ng, Sze; Ahern, Susannah; Cooter, Rodney; Hopper, Ingrid
2017-12-03
The medical tourism industry, and in particular cosmetic tourism for breast augmentation, is becoming an increasingly popular global phenomenon. The objective of this study is to determine the extent of medical literature and the patient risk profiles associated with cosmetic tourism for breast augmentation both locally and abroad. OVID MEDLINE, OVID Embase, Cochrane Central and Proquest electronic databases. The search was conducted through to April 2017. Studies pertaining entirely or partly to cosmetic tourism for breast augmentation were considered for inclusion. Exclusion criteria included non-English articles, studies relating to non-cosmetic or non-implant breast augmentation, and studies that did not separately report on findings associated with breast augmentation abroad. We identified 17 observational studies. Common destinations included Europe, South America and South East Asia. Infectious complications were common. Wound dehiscence and aesthetic dissatisfaction also featured. Catastrophic outcomes such as sepsis, intubation and ventilation, radical bilateral mastectomy, irreversible hypoxic brain injury and death were also reported. There were expectations that home country health systems would treat complications and provide non-medically indicated revision procedures. The burden on home country health systems was evident from a public health perspective. Determining the extent of cosmetic tourism for breast augmentation, including outcomes and complications, will help to inform Australian patients who this seek procedure abroad. Furthermore, it will aid in better understanding the health system implications and may help to guide future research and public health interventions both locally and internationally. © 2017 Royal Australasian College of Surgeons.
Fenn, Timothy D; Schnieders, Michael J; Mustyakimov, Marat; Wu, Chuanjie; Langan, Paul; Pande, Vijay S; Brunger, Axel T
2011-04-13
Most current crystallographic structure refinements augment the diffraction data with a priori information consisting of bond, angle, dihedral, planarity restraints, and atomic repulsion based on the Pauli exclusion principle. Yet, electrostatics and van der Waals attraction are physical forces that provide additional a priori information. Here, we assess the inclusion of electrostatics for the force field used for all-atom (including hydrogen) joint neutron/X-ray refinement. Two DNA and a protein crystal structure were refined against joint neutron/X-ray diffraction data sets using force fields without electrostatics or with electrostatics. Hydrogen-bond orientation/geometry favors the inclusion of electrostatics. Refinement of Z-DNA with electrostatics leads to a hypothesis for the entropic stabilization of Z-DNA that may partly explain the thermodynamics of converting the B form of DNA to its Z form. Thus, inclusion of electrostatics assists joint neutron/X-ray refinements, especially for placing and orienting hydrogen atoms. Copyright © 2011 Elsevier Ltd. All rights reserved.
Exploration Augmentation Module Project
National Aeronautics and Space Administration — The Exploration Augmentation Module (EAM) project goal is to design and deliver a flight module that is to be deployed to Earth-Lunar Distant Retrograde Orbit (DRO)....
Intravenous alpha-1 antitrypsin augmentation therapy: systematic review
DEFF Research Database (Denmark)
Gøtzsche, Peter C; Johansen, Helle Krogh
2010-01-01
We reviewed the benefits and harms of augmentation therapy with alpha-1 antitrypsin in patients with alpha-1 antitrypsin deficiency and lung disease. We searched for randomised trials comparing augmentation therapy with placebo or no treatment in PubMed and ClinicalTrials (7 January 2010). Two...... (difference 1.14 g/l; 95% confidence interval 0.14 to 2.14; p = 0.03) over the total course of the trials. Augmentation therapy with alpha-1 antitrypsin cannot be recommended in view of the lack of evidence of clinical benefit and the cost of treatment....
Krieckaert, C.L.; Bartelds, G.M.; Lems, W.F.; Wolbink, G.J.
2010-01-01
Therapeutic monoclonal antibodies have revolutionized the treatment of various inflammatory diseases. Immunogenicity against these antibodies has been shown to be clinically important: it is associated with shorter response duration because of diminishing concentrations in the blood and with
Pemanfaatan Augmented Reality Pada Permainan Othello
Directory of Open Access Journals (Sweden)
Rendy Layman Aguston
2016-11-01
Full Text Available Perkembangan teknologi telah mengubah cara pengerjaan suatu pekerjaan dari cara konvensional menjadi cara yang lebih praktis. Dengan hadirnya teknologi Augmented Reality, cara bermain yang menggunakan pion dan membalikkan pion musuh secara manual menjadi lebih mudah dalam memainkan permainan selain juga dapat berinteraksi langsung. Pembuatan permainan Othello menggunakan program Unity dengan framework Vuforia untuk mewujudkan Augmented Reality pada permainan Othello. Untuk menerapkan Augmented Reality dengan baik, dibutuhkan papan permainan sebagai image target yang sesuai dengan kriteria, jenis kamera yang digunakan, jarak kamera terhadap papan permainan, intensitas cahaya yang ditangkap kamera, serta tingkat sensitivitas tombol virtual. Pada permainan Othello ini tersedia fitur komputer yang menggunakan algoritma Alpha Beta Pruning dengan 3 level kedalaman yang menggunakan perhitungan fungsi evaluasi berupa mobility, potential mobility dan penguasaan corner yang menghasilkan kemenangan mencapai 73,33% dari 15 kali uji coba terhadap aplikasi Othello serupa dan 78,34% dari 37 kali uji coba terhadap user.
Directory of Open Access Journals (Sweden)
Widiastuti R
2013-06-01
Full Text Available An oxytetracycline-tolidin-bovine serum albumin (OTC-tolidin-BSA-conjugate was synthezed as immunogen for producing specific antibodies in immunized rabbits that would be used as reagent for development of OTC residue detection with enzym-linked immunoassays technique. The immunogen was prepared through diazotization tolidin and subsequently reacted with OTC. The red purple immunogen of OTC-tolidin-BSA absorbed at wave lengths of 277 nm and 488 nm under UV screening absorbances and confirmation with the high performance liquid chromatography (HPLC showed the absence of peak at retention time of 3.46 minutes. Characaterized result with SDS-PAGE showed the molecular weight of the OTC-tolidin-BSA at 69.79 kDA. Subsequently, the immunogen was immunized into New Zealand rabbits in order to produce the polyclonal antibodies. The antibodies were purified using a protein A sepharose column. The OD optimum responses of 0.92 to 1.20 were obtained from the second fractionation at dilution of 1/1000 by titrating the antibodies and OTC-tolidin-BSA coating antigen at concentration of 10 µg/mL on several bleeding times.
Directory of Open Access Journals (Sweden)
Lin Chen-Si
2012-02-01
Full Text Available Abstract Background It is widely understood that tumor cells express tumor-associated antigens (TAAs, of which many are usually in low immunogenicity; for example, carcinoembryonic antigen (CEA is specifically expressed on human colon cancer cells and is viewed as a low-immunogenic TAA. How to activate host immunity against specific TAAs and to suppress tumor growth therefore becomes important in cancer therapy development. Results To enhance the immune efficiency of CEA in mice that received, we fused a partial CEA gene with exogenous SARS-CoV fragments. Oral vaccination of an attenuated Salmonella typhimurium strain transformed with plasmids encoding CEA-SARS-CoV fusion gene into BALB/c mice elicited significant increases in TNF-α and IL-10 in the serum. In addition, a smaller tumor volume was observed in CT26/CEA-bearing mice who received CEA-SARS-CoV gene therapy in comparison with those administered CEA alone. Conclusion The administration of fusing CEA-SARS-CoV fragments may provide a promising strategy for strengthening the anti-tumor efficacy against low-immunogenic endogenous tumor antigens.
Mobile Augmented Note-taking to Support Operating Physical Devices
Liu , Can; Diehl , Jonathan; Huot , Stéphane; Borchers , Jan
2011-01-01
Mobile Augmented Reality: Design Issues and Opportunities - 1st Workshop on Mobile Augmented Reality, MobileHCI 2011; In this paper we propose an approach to assist operating physical devices with mobile augmented reality techniques. We propose ideas of interaction techniques, which allow users to put self-authored information as notes onto physical objects. We present the design of two example applications aiming at solving problems from different aspects of physical operations.
Dash, Hirak Ranjan; Das, Surajit
2018-02-01
Forensic biology is a sub-discipline of biological science with an amalgam of other branches of science used in the criminal justice system. Any nucleated cell/tissue harbouring DNA, either live or dead, can be used as forensic exhibits, a source of investigation through DNA typing. These biological materials of human origin are rich source of proteins, carbohydrates, lipids, trace elements as well as water and, thus, provide a virtuous milieu for the growth of microbes. The obstinate microbial growth augments the degradation process and is amplified with the passage of time and improper storage of the biological materials. Degradation of these biological materials carriages a huge challenge in the downstream processes of forensic DNA typing technique, such as short tandem repeats (STR) DNA typing. Microbial degradation yields improper or no PCR amplification, heterozygous peak imbalance, DNA contamination from non-human sources, degradation of DNA by microbial by-products, etc. Consequently, the most precise STR DNA typing technique is nullified and definite opinion can be hardly given with degraded forensic exhibits. Thus, suitable precautionary measures should be taken for proper storage and processing of the biological exhibits to minimize their decaying process by micro-organisms.
International Nuclear Information System (INIS)
Sharpe, Sally; Hanke, Tomas; Tinsley-Bown, Anne; Dennis, Mike; Dowall, Stuart; McMichael, Andrew; Cranage, Martin
2003-01-01
Systemically administered DNA encoding a recombinant human immunodeficiency virus (HIV) derived immunogen effectively primes a cytotoxic T lymphocyte (CTL) response in macaques. In this further pilot study we have evaluated mucosal delivery of DNA as an alternative priming strategy. Plasmid DNA, pTH.HW, encoding a multi-CTL epitope gene, was incorporated into poly(D,L-lactic-co-glycolic acid) microparticles of less than 10 μm in diameter. Five intrarectal immunizations failed to stimulate a circulating vaccine-specific CTL response in 2 Mamu-A*01 + rhesus macaques. However, 1 week after intradermal immunization with a cognate modified vaccinia virus Ankara vaccine MVA.HW, CTL responses were detected in both animals that persisted until analysis postmortem, 12 weeks after the final boost. In contrast, a weaker and less durable response was seen in an animal vaccinated with the MVA construct alone. Analysis of lymphoid tissues revealed a disseminated CTL response in peripheral and regional lymph nodes but not the spleen of both mucosally primed animals
Riccardo, Federica; Iussich, Selina; Maniscalco, Lorella; Lorda Mayayo, Saray; La Rosa, Giuseppe; Arigoni, Maddalena; De Maria, Raffaella; Gattino, Francesca; Lanzardo, Stefania; Lardone, Elena; Martano, Marina; Morello, Emanuela; Prestigio, Simone; Fiore, Alessandra; Quaglino, Elena; Zabarino, Sara; Ferrone, Soldano; Buracco, Paolo; Cavallo, Federica
2014-07-15
Due to the many similarities with its human counterpart, canine malignant melanoma (cMM) is a valuable model in which to assess the efficacy of novel therapeutic strategies. The model is herein used to evaluate the immunogenicity, safety, and therapeutic efficacy of a human chondroitin sulfate proteoglycan-4 (hCSPG4) DNA-based vaccine. The fact that homology between hCSPG4 and cCSPG4 amino-acidic sequences stands at more than 80% provides the rationale for using an hCSPG4 DNA vaccine in the cMM model. Dogs with stage II-III surgically resected CSPG4-positive oral MM were subjected to monthly intramuscular plasmid administration, which was followed immediately by electroporation (electrovaccination) for at least 6, and up to 20, months. The immunogenicity, safety, and therapeutic efficacy of the vaccine have been evaluated. hCSPG4 electrovaccination caused no clinically relevant local or systemic side effects and resulted in significantly longer overall and disease-free survival times in 14 vaccinated dogs as compared with 13 nonvaccinated controls. All vaccinated dogs developed antibodies against both hCSPG4 and cCSPG4. Seven vaccinated dogs were also tested for a cCSPG4-specific T-cell response and only two gave a detectable interferon (IFN)γ response. Xenogeneic electrovaccination against CSPG4 is able to overcome host unresponsiveness to the "self" antigen and seems to be effective in treating cMM, laying the foundation for its translation to a human clinical setting. ©2014 American Association for Cancer Research.
Schmalstieg, Dieter; Langlotz, Tobias; Billinghurst, Mark
Augmented Reality (AR) was first demonstrated in the 1960s, but only recently have technologies emerged that can be used to easily deploy AR applications to many users. Camera-equipped cell phones with significant processing power and graphics abilities provide an inexpensive and versatile platform for AR applications, while the social networking technology of Web 2.0 provides a large-scale infrastructure for collaboratively producing and distributing geo-referenced AR content. This combination of widely used mobile hardware and Web 2.0 software allows the development of a new type of AR platform that can be used on a global scale. In this paper we describe the Augmented Reality 2.0 concept and present existing work on mobile AR and web technologies that could be used to create AR 2.0 applications.
Qian, Feng; Wu, Yimin; Muratova, Olga; Zhou, Hong; Dobrescu, Gelu; Duggan, Peter; Lynn, Lambert; Song, Guanhong; Zhang, Yanling; Reiter, Karine; MacDonald, Nicholas; Narum, David L; Long, Carole A; Miller, Louis H; Saul, Allan; Mullen, Gregory E D
2007-05-16
Conjugation of polysaccharides to carrier proteins has been a successful approach for producing safe and effective vaccines. In an attempt to increase the immunogenicity of two malarial vaccine candidate proteins of Plasmodium falciparum, apical membrane antigen 1 (AMA1) to a blood stage vaccine candidate and surface protein 25 (Pfs25) a mosquito stage vaccine candidate, were each independently chemically conjugated to the mutant, nontoxic Pseudomonas aeruginosa ExoProtein A (rEPA). AMA1 is a large (66kD) relatively good immunogen in mice; Pfs25 is a poorly immunogenic protein when presented on alum to mice. Mice were immunized on days 0 and 28 with AMA1- or Pfs25-rEPA conjugates or unconjugated AMA1 or Pfs25, all formulated on Alhydrogel. Remarkably, sera from mice 14 days after the second immunization with Pfs25-rEPA conjugates displayed over a 1000-fold higher antibody titers as compared to unconjugated Pfs25. In contrast, AMA1 conjugated under the same conditions induced only a three-fold increase in antibody titers. When tested for functional activity, antibodies elicited by the AMA1-rEPA inhibited invasion of erythrocytes by blood-stage parasites and antibodies elicited by the Pfs25-rEPA conjugates blocked the development of the sexual stage parasites in the mosquito midgut. These results demonstrate that conjugation to rEPA induces a marked improvement in the antibody titer in mice for the poor immunogen (Pfs25) and for the larger protein (AMA1). These conjugates now need to be tested in humans to determine if mice are predictive of the response in humans.
Arancibia, Sergio; Del Campo, Miguel; Nova, Esteban; Salazar, Fabián; Becker, María Inés
2012-03-01
Hemocyanins, which boost the immune system of mammals, have been used as carrier-adjuvants to promote Ab production against haptens and peptides, as immunostimulants during therapy for bladder carcinoma and as a component in therapeutic vaccines for cancer. These biomedical applications have led to growing interest in obtaining hemocyanins with high immunogenicity. Here, we study the immunological properties of a modified oxidized Concholepas concholepas hemocyanin (Ox-CCH) obtained by the oxidation of its carbohydrates using sodium periodate. We assessed the internalization of Ox-CCH into DCs and its immunogenicity and antitumor effects. Transmission electron microscopy showed no changes in Ox-CCH quaternary structure with respect to native CCH, although proteolytic treatment followed by SDS-PAGE analysis demonstrated that Schiff bases were formed. Interestingly, DCs internalized Ox-CCH faster than CCH, mainly through macropinocytosis. During this process, Ox-CCH remained inside endosome-like structures for a longer period. Mouse immunization experiments demonstrated that Ox-CCH is more immunogenic and a better carrier than CCH. Moreover, Ox-CCH showed a significant antitumor effect in the B16F10 melanoma model similar to that produced by CCH, inducing IFN-γ secretion. Together, these data demonstrate that the aldehydes formed by the periodate oxidation of sugar moieties stabilizes the CCH structure, increasing its adjuvant/immunostimulatory carrier effects. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Aarden, Lucien; Ruuls, Sigrid R.; Wolbink, Gertjan
2008-01-01
To date, millions of people have been treated with therapeutic monoclonal antibodies (TmAbs) for various indications. It is becoming increasingly clear that TmAbs can be immunogenic, which may reduce efficacy or induce adverse effects. Over the years, the importance of antibody formation has been
Personalized augmented reality for anatomy education.
Ma, Meng; Fallavollita, Pascal; Seelbach, Ina; Von Der Heide, Anna Maria; Euler, Ekkehard; Waschke, Jens; Navab, Nassir
2016-05-01
Anatomy education is a challenging but vital element in forming future medical professionals. In this work, a personalized and interactive augmented reality system is developed to facilitate education. This system behaves as a "magic mirror" which allows personalized in-situ visualization of anatomy on the user's body. Real-time volume visualization of a CT dataset creates the illusion that the user can look inside their body. The system comprises a RGB-D sensor as a real-time tracking device to detect the user moving in front of a display. In addition, the magic mirror system shows text information, medical images, and 3D models of organs that the user can interact with. Through the participation of 7 clinicians and 72 students, two user studies were designed to respectively assess the precision and acceptability of the magic mirror system for education. The results of the first study demonstrated that the average precision of the augmented reality overlay on the user body was 0.96 cm, while the results of the second study indicate 86.1% approval for the educational value of the magic mirror, and 91.7% approval for the augmented reality capability of displaying organs in three dimensions. The usefulness of this unique type of personalized augmented reality technology has been demonstrated in this paper. © 2015 Wiley Periodicals, Inc.
Agarwal, Raksheeth; Wahid, Mardiastuti H; Yausep, Oliver E; Angel, Sharon H; Lokeswara, Angga W
2017-01-01
to assess the immunogenicity and safety of CYD-tetravalent dengue vaccine (CYD-TDV) in children. comprehensive literature searches were conducted on various databases. Randomized-controlled trials on children with CYD-TDV as intervention were selected based on inclusion and exclusion criteria. Data extracted from selected trials included safety of vaccine and immunogenicity in terms of Geometric Mean Titres (GMT) of antibodies. six clinical trials were selected based on preset criteria. GMT values were obtained using 50% Plaque Reduction Neutralization Test (PRNT) and safety was semi-quantitatively assessed based on adverse effects. Additional data processing was done to obtain a better understanding on the trends among the studies. The results showed that the groups vaccinated with CYD-TDV showed higher immunogenicity against dengue virus antigens than the control groups. Safety results were satisfactory in all trials, and most severe side effects were unrelated to the vaccine. CYD-TDV is both effective and safe for patients in endemic regions. This gives promise for further development and large-scale research on this vaccine to assess its efficacy in decreasing dengue prevalence, and its pervasive implementation in endemic countries, such as Indonesia.
Safety and Immunogenicity of a Mycoplasma ovipneumoniae bacterin for domestic sheep (Ovis aries).
Ziegler, Jessie C; Lahmers, Kevin K; Barrington, George M; Parish, Steven M; Kilzer, Katherine; Baker, Katherine; Besser, Thomas E
2014-01-01
Mortality from epizootic pneumonia is hindering re-establishment of bighorn sheep populations in western North America. Mycoplasma ovipneumoniae, a primary agent of this disease, is frequently carried asymptomatically by the domestic sheep and goats that constitute the reservoir of this agent for transmission to bighorn sheep. Our long-term objective is to reduce the risk of M. ovipneumoniae infection of bighorn sheep; one approach to this objective is to control the pathogen in its reservoir hosts. The safety and immunogenicity of M. ovipneumoniae for domestic sheep was evaluated in three experimental immunization protocols: 1) live M. ovipneumoniae (50 ug protein); 2) killed M. ovipneumoniae (50 ug whole cell protein) in oil adjuvant; and 3) killed M. ovipneumoniae (250 ug whole cell protein) in oil adjuvant. Immunogenicity was assessed by two serum antibody measures: competitive enzyme-linked immunosorbent assay (cELISA) (experiments 1-3) and serum growth inhibition (Experiment 3). Passive immunogenicity was also assessed in the third experiment using the same assays applied to blood samples obtained from the lambs of immunized ewes. Adverse reactions to immunization were generally minor, but local reactions were regularly observed at immunization sites with bacterins in oil adjuvants. No evidence of M. ovipneumoniae specific antibody responses were observed in the first or second experiments and no resistance to colonization was observed in the first experiment. However, the ewes in the third experiment developed strong cELISA serum antibody responses and significant serum M. ovipneumoniae inhibition activity, and these responses were passively transferred to their lambs. The results of these trials indicate that immunization with relatively large antigenic mass combined with an adjuvant is capable of inducing strong active antibody responses in ewes and passively immunizing lambs.
Safety and Immunogenicity of a Mycoplasma ovipneumoniae bacterin for domestic sheep (Ovis aries.
Directory of Open Access Journals (Sweden)
Jessie C Ziegler
Full Text Available BACKGROUND: Mortality from epizootic pneumonia is hindering re-establishment of bighorn sheep populations in western North America. Mycoplasma ovipneumoniae, a primary agent of this disease, is frequently carried asymptomatically by the domestic sheep and goats that constitute the reservoir of this agent for transmission to bighorn sheep. Our long-term objective is to reduce the risk of M. ovipneumoniae infection of bighorn sheep; one approach to this objective is to control the pathogen in its reservoir hosts. METHODS: The safety and immunogenicity of M. ovipneumoniae for domestic sheep was evaluated in three experimental immunization protocols: 1 live M. ovipneumoniae (50 ug protein; 2 killed M. ovipneumoniae (50 ug whole cell protein in oil adjuvant; and 3 killed M. ovipneumoniae (250 ug whole cell protein in oil adjuvant. Immunogenicity was assessed by two serum antibody measures: competitive enzyme-linked immunosorbent assay (cELISA (experiments 1-3 and serum growth inhibition (Experiment 3. Passive immunogenicity was also assessed in the third experiment using the same assays applied to blood samples obtained from the lambs of immunized ewes. RESULTS AND CONCLUSIONS: Adverse reactions to immunization were generally minor, but local reactions were regularly observed at immunization sites with bacterins in oil adjuvants. No evidence of M. ovipneumoniae specific antibody responses were observed in the first or second experiments and no resistance to colonization was observed in the first experiment. However, the ewes in the third experiment developed strong cELISA serum antibody responses and significant serum M. ovipneumoniae inhibition activity, and these responses were passively transferred to their lambs. The results of these trials indicate that immunization with relatively large antigenic mass combined with an adjuvant is capable of inducing strong active antibody responses in ewes and passively immunizing lambs.
Fox, B A; Drury, M; Hu, H M; Cao, Z; Huntzicker, E G; Qie, W; Urba, W J
1998-01-01
Direct intratumoral injection of a lipid/DNA complex encoding an allogeneic major histocompatibility complex (MHC) class I molecule leads to regression of both an immunogenic murine tumor and also melanoma lesions in some patients. We have sought to understand the mechanism(s) for this augmentation of antitumor activity. While optimizing parameters for in vitro gene transfer into the D5 subclone of B16BL6, it was noted that lipofected tumors not only expressed the new alloantigen but also exhibited increased expression of endogenous MHC class I, both H-2 Kb and H-2 Db. This increase in expression was not restricted to the small percentage of cells that expressed the transfected gene, but appeared to affect the majority of cells in culture. Class I expression was not increased by lipopolysaccharide, DNA alone, lipid, or lipid/lipopolysaccharide mixtures. Enhanced class I expression required a DNA/lipid complex and was greatest when parameters optimized for gene transfer of the alloantigen were used. All DNA plasmids tested had this effect, including one plasmid whose DNA was not transcribed because it lacked an expression cassette. Because of the critical role that MHC class I antigens play in immune recognition, we propose that lipid complex-mediated gene transfer may provide immunological advantages beyond those that are attributable to expression of the specific gene transferred.
Graziani, Gina M; Angel, Jonathan B
2016-07-01
Although current antiretroviral therapy (ART) has transformed HIV infection into a chronic, manageable disease, ART does not cure HIV infection. Furthermore, the majority of the world's infected individuals live in resource-limited countries in which access to ART is limited. Thus, the development of an effective therapeutic HIV vaccine would be an invaluable treatment alternative. Developed by the late Dr. Jonas Salk, HIV-1 Immunogen (Remune®) is a candidate therapeutic vaccine that has been studied in thousands of HIV-infected individuals in more than a dozen clinical trials during almost three decades. This Drug Evaluation, which summarizes the results of these trials that have shown the vaccine to be safe and immunogenic, also discusses the contradictory and controversial conclusions drawn from the phases 2, 2/3 and 3 trials that assessed the clinical efficacy of this vaccine. Given the lack of unequivocal clinical benefits of HIV-1 Immunogen despite almost 30 years of extensive testing, it does not appear, in our view, that this vaccine is a clinically effective immunotherapy. However, inclusion of this vaccine in the newly proposed 'Kick/Shock and Kill' strategy for HIV eradication, or use as a prophylactic vaccine, could be considered for future trials.
Directory of Open Access Journals (Sweden)
Arvind Chhabra
2017-08-01
Full Text Available Donor-specific induced pluripotent stem cells (iPSCs offer opportunities for personalized cell replacement therapeutic approaches due to their unlimited self-renewal potential and ability to differentiate into different somatic cells. A significant progress has been made toward generating iPSC lines that are free of integrating viral vectors, development of xeno-free culture conditions, and differentiation of pluripotent stem cells (PSCs into functional somatic cell lineages. Since donor-specific iPSC lines are genetically identical to the individual, they are expected to be immunologically matched and these iPSC lines and their cellular derivatives are not expected to be immunologically rejected. However, studies in mouse models, utilizing rejection of teratomas as a model, have claimed that syngenic iPSC lines, especially the iPSC lines derived with integrating viral vectors, could be inherently immunogenic. This manuscript reviews current understanding of inherent immunogenicity of PSC lines, especially that of the human iPSC lines and their cellular derivatives, and strategies to overcome it.
Yin, Liusong; Chen, Xiaoying; Vicini, Paolo; Rup, Bonita; Hickling, Timothy P
2015-06-01
Therapeutic protein products (TPPs) are of considerable value in the treatment of a variety of diseases, including cancer, hemophilia, and autoimmune diseases. The success of TPP mainly results from prolonged half-life, increased target specificity and decreased intrinsic toxicity compared with small molecule drugs. However, unwanted immune responses against TPP, such as generation of anti-drug antibody, can impact both drug efficacy and patient safety, which has led to requirements for increased monitoring in regulatory studies and clinical practice, termination of drug development, or even withdrawal of marketed products. We present an overview of current knowledge on immunogenicity of TPP and its impact on efficacy and safety. We also discuss methods for measurement and prediction of immunogenicity and review both product-related and patient-related risk factors that affect its development, and efforts that may be taken to mitigate it. Lastly, we discuss gaps in knowledge and technology and what is needed to fill these. Copyright © 2015 Elsevier Inc. All rights reserved.
Bautista, Ami C; Zhou, Lei; Jawa, Vibha
2013-10-01
Immunogenicity support during nonclinical biotherapeutic development can be resource intensive if supported by conventional methodologies. A universal indirect species-specific immunoassay can eliminate the need for biotherapeutic-specific anti-drug antibody immunoassays without compromising quality. By implementing the R's of sustainability (reduce, reuse, rethink), conservation of resources and greener laboratory practices were achieved in this study. Statistical analysis across four biotherapeutics supported identification of consistent product performance standards (cut points, sensitivity and reference limits) and a streamlined universal anti-drug antibody immunoassay method implementation strategy. We propose an efficient, fit-for-purpose, scientifically and statistically supported nonclinical immunogenicity assessment strategy. Utilization of a universal method and streamlined validation, while retaining comparability to conventional immunoassays and meeting the industry recommended standards, provides environmental credits in the scientific laboratory. Collectively, individual reductions in critical material consumption, energy usage, waste and non-environment friendly consumables, such as plastic and paper, support a greener laboratory environment.
Mitochondrial DNA analysis of two southern African elephant populations
Directory of Open Access Journals (Sweden)
M.F. Essop
1996-08-01
Full Text Available The modern view is that there are at most only two valid forms of the African elephant namely Loxodonta qfricana africana, the bush elephant, and L.a. cyclotis, the forest elephant (Ansell 1974; Meester et al. 1986. The Knysna elephant which was also described as a separate sub-species is now almost extinct. Plans to augment the remnant population by introducing other animals must take into account the taxonomic questions and issue of conserving elephant gene pools (Greig 1982a. Mitochondrial DNA (mtDNA restriction fragment-size comparisons were performed on specimens from the Kruger National Park and the Addo Elephant National Park. If the Addo population's results are extrapolated to the Knysna population, it may be concluded that there is no genetic evidence for the Kruger and Knysna elephant populations to be considered as different sub-species.
Augmented reality based real-time subcutaneous vein imaging system.
Ai, Danni; Yang, Jian; Fan, Jingfan; Zhao, Yitian; Song, Xianzheng; Shen, Jianbing; Shao, Ling; Wang, Yongtian
2016-07-01
A novel 3D reconstruction and fast imaging system for subcutaneous veins by augmented reality is presented. The study was performed to reduce the failure rate and time required in intravenous injection by providing augmented vein structures that back-project superimposed veins on the skin surface of the hand. Images of the subcutaneous vein are captured by two industrial cameras with extra reflective near-infrared lights. The veins are then segmented by a multiple-feature clustering method. Vein structures captured by the two cameras are matched and reconstructed based on the epipolar constraint and homographic property. The skin surface is reconstructed by active structured light with spatial encoding values and fusion displayed with the reconstructed vein. The vein and skin surface are both reconstructed in the 3D space. Results show that the structures can be precisely back-projected to the back of the hand for further augmented display and visualization. The overall system performance is evaluated in terms of vein segmentation, accuracy of vein matching, feature points distance error, duration times, accuracy of skin reconstruction, and augmented display. All experiments are validated with sets of real vein data. The imaging and augmented system produces good imaging and augmented reality results with high speed.
Virtual, augmented reality and serious games for healthcare
Jain, Lakhmi; Anderson, Paul
2014-01-01
There is a tremendous interest among researchers for the development of virtual, augmented reality and games technologies due to their widespread applications in medicine and healthcare. To date the major applications of these technologies include medical simulation, telemedicine, medical and healthcare training, pain control, visualisation aid for surgery, rehabilitation in cases such as stroke, phobia, and trauma therapies. Many recent studies have identified the benefits of using Virtual Reality, Augmented Reality, or serious games in a variety of medical applications. This research volume on Virtual, Augmented Reality and Serious Games for Healthcare 1 offers an insightful introduction to the theories, development and applications of virtual, augmented reality and digital games technologies in medical and clinical settings and healthcare in general. It is divided into six sections: section one presents a selection of applications in medical education and healthcare management; Section two relates to th...
An Integrative Introduction to Human Augmentation Science
Alicea, Bradly
2018-01-01
Human Augmentation (HA) spans several technical fields and methodological approaches, including Experimental Psychology, Human-Computer Interaction, Psychophysiology, and Artificial Intelligence. Augmentation involves various strategies for optimizing and controlling cognitive states, which requires an understanding of biological plasticity, dynamic cognitive processes, and models of adaptive systems. As an instructive lesson, we will explore a few HA-related concepts and outstanding issues. ...
Medical imaging and augmented reality. Proceedings
International Nuclear Information System (INIS)
Dohi, Takeyoshi; Sakuma, Ichiro; Liao, Hongen
2008-01-01
This book constitutes the refereed proceedings of the 4th International Workshop on Medical Imaging and Augmented Reality, MIAR 2008, held in Tokyo, Japan, in August 2008. The 44 revised full papers presented together with 3 invited papers were carefully reviewed and selected from 90 submissions. The papers are organized in topical sections on surgical planning and simulation, medical image computing, image analysis, shape modeling and morphometry, image-guided robotics, image-guided intervention, interventional imaging, image registration, augmented reality, and image segmentation. (orig.)
Medical imaging and augmented reality. Proceedings
Energy Technology Data Exchange (ETDEWEB)
Dohi, Takeyoshi [Tokyo Univ. (Japan). Dept. of Mechano-Informatics; Sakuma, Ichiro [Tokyo Univ. (Japan). Dept. of Precision Engineering; Liao, Hongen (eds.) [Tokyo Univ. (Japan). Dept. of Bioengineering
2008-07-01
This book constitutes the refereed proceedings of the 4th International Workshop on Medical Imaging and Augmented Reality, MIAR 2008, held in Tokyo, Japan, in August 2008. The 44 revised full papers presented together with 3 invited papers were carefully reviewed and selected from 90 submissions. The papers are organized in topical sections on surgical planning and simulation, medical image computing, image analysis, shape modeling and morphometry, image-guided robotics, image-guided intervention, interventional imaging, image registration, augmented reality, and image segmentation. (orig.)
Augmentation of French grunt diet description using combined visual and DNA-based analyses
Hargrove, John S.; Parkyn, Daryl C.; Murie, Debra J.; Demopoulos, Amanda W.J.; Austin, James D.
2012-01-01
Trophic linkages within a coral-reef ecosystem may be difficult to discern in fish species that reside on, but do not forage on, coral reefs. Furthermore, dietary analysis of fish can be difficult in situations where prey is thoroughly macerated, resulting in many visually unrecognisable food items. The present study examined whether the inclusion of a DNA-based method could improve the identification of prey consumed by French grunt, Haemulon flavolineatum, a reef fish that possesses pharyngeal teeth and forages on soft-bodied prey items. Visual analysis indicated that crustaceans were most abundant numerically (38.9%), followed by sipunculans (31.0%) and polychaete worms (5.2%), with a substantial number of unidentified prey (12.7%). For the subset of prey with both visual and molecular data, there was a marked reduction in the number of unidentified sipunculans (visual – 31.1%, combined &ndash 4.4%), unidentified crustaceans (visual &ndash 15.6%, combined &ndash 6.7%), and unidentified taxa (visual &ndash 11.1%, combined &ndash 0.0%). Utilising results from both methodologies resulted in an increased number of prey placed at the family level (visual &ndash 6, combined &ndash 33) and species level (visual &ndash 0, combined &ndash 4). Although more costly than visual analysis alone, our study demonstrated the feasibility of DNA-based identification of visually unidentifiable prey in the stomach contents of fish.
Cognitive Cost of Using Augmented Reality Displays.
Baumeister, James; Ssin, Seung Youb; ElSayed, Neven A M; Dorrian, Jillian; Webb, David P; Walsh, James A; Simon, Timothy M; Irlitti, Andrew; Smith, Ross T; Kohler, Mark; Thomas, Bruce H
2017-11-01
This paper presents the results of two cognitive load studies comparing three augmented reality display technologies: spatial augmented reality, the optical see-through Microsoft HoloLens, and the video see-through Samsung Gear VR. In particular, the two experiments focused on isolating the cognitive load cost of receiving instructions for a button-pressing procedural task. The studies employed a self-assessment cognitive load methodology, as well as an additional dual-task cognitive load methodology. The results showed that spatial augmented reality led to increased performance and reduced cognitive load. Additionally, it was discovered that a limited field of view can introduce increased cognitive load requirements. The findings suggest that some of the inherent restrictions of head-mounted displays materialize as increased user cognitive load.
Yang, Qian; Roehrl, Michael H.; Wang, Julia Y.
2018-01-01
We hypothesized that cancer tissue immunogens – antigens capable of inducing specific antibody production in patients – are promising targets for development of precision diagnostics and humoral immunotherapies. We developed an innovative immuno-proteomic strategy and identified new immunogenic markers of colon cancer. Proteins from cancers and matched normal tissues were separated by 2D gel electrophoresis and blotted with serum antibodies from the same patients. Antibody-reactive proteins were sequenced by mass spectrometry and validated by Western blotting and immunohistochemistry. 170 serum antibody-reactive proteins were identified only in cancerous but not matched normal. Among these, proteasome subunit alpha type 1 (PSA1), leucine aminopeptidase 3 (LAP3), annexin A3 (ANXA3), and maspin (serpin B5) were reproducibly found in tissues from three patients. Differential expression patterns were confirmed in samples from eight patients with various stages of colon adenocarcinoma and liver metastases. These tumor-resident proteins and/or their associated serum antibodies may be promising markers for colon cancer screening and early diagnosis. Furthermore, tumor tissue-specific antibodies could potentially be exploited as immunotherapeutic targets against cancer. More generally, proteomic profiling of antibody-inducing cancer-associated immunogens represents a powerful generic method for uncovering the tumor antigen-ome, i.e., the totality of immunogenic tumor-associated proteins. PMID:29423100
Adaptive multimodal interaction in mobile augmented reality: A conceptual framework
Abidin, Rimaniza Zainal; Arshad, Haslina; Shukri, Saidatul A'isyah Ahmad
2017-10-01
Recently, Augmented Reality (AR) is an emerging technology in many mobile applications. Mobile AR was defined as a medium for displaying information merged with the real world environment mapped with augmented reality surrounding in a single view. There are four main types of mobile augmented reality interfaces and one of them are multimodal interfaces. Multimodal interface processes two or more combined user input modes (such as speech, pen, touch, manual gesture, gaze, and head and body movements) in a coordinated manner with multimedia system output. In multimodal interface, many frameworks have been proposed to guide the designer to develop a multimodal applications including in augmented reality environment but there has been little work reviewing the framework of adaptive multimodal interface in mobile augmented reality. The main goal of this study is to propose a conceptual framework to illustrate the adaptive multimodal interface in mobile augmented reality. We reviewed several frameworks that have been proposed in the field of multimodal interfaces, adaptive interface and augmented reality. We analyzed the components in the previous frameworks and measure which can be applied in mobile devices. Our framework can be used as a guide for designers and developer to develop a mobile AR application with an adaptive multimodal interfaces.
Ling, Yong; Li, Shaowen; Yang, Junjing; Yuan, Jilei; He, Cheng
2011-01-01
Lycium barbarum polysaccharides (LBP) can stimulate moderate immune responses therefore could potentially be used as a substitute for oil adjuvants in veterinary vaccines. In the present study, it was shown that the isolated active component of LBP3a, combined with a DNA vaccine encoding the major outer membrane protein (MOMP) of Chlamydophila abortus, induced protection in mice against challenge. Sixty BALB/c mice were randomly assigned to 5 groups. Sub-fractions of polysaccharide LBP3a, at 12.5, 25 and 50 mg/kg concentrations, respectively, were mixed with a pCI-neo::MOMP (pMOMP) vaccine. Mice administrated with pCI-neo + LBP3a were served as a control. All mice were inoculated at day 0, 14, and 28, and challenged on day 44. The effects of LBp3a on serum antibody levels, in vitro lymphocyte proliferation, the activity of interleaukin-2 (IL-2), interferon-γ (IFN-γ), tumor necrosis factor α(TNF-α)and chlamydia clearance were determined. A combination of DNA vaccine and LBP3a induced significantly higher antibody levels in mice, higher T cell proliferation and higher levels of IFN-γ and IL-2. Mice immunized with DNA and LBP3a also showed significantly higher levels of chlamydia clearance in mice spleens and a greater Th1 immune response. The immunoenhancement induced by 25 mg/kg LBP3a is more effective than that induced by a 12.5 and 50 mg/kg. This implies that LBP3a at 25 mg/kg has a high potential to be used as an effective adjuvant with a DNA vaccine against swine Chlamydophila abortus.
Designing and modeling of complex DNA vaccine based on tropomyosin protein of Boophilus genus tick.
Ranjbar, Mohamamd Mahdi; Gupta, Shishir K; Ghorban, Khodayar; Nabian, Sedigheh; Sazmand, Alireza; Taheri, Mohammad; Esfandyari, Sahar; Taheri, Maryam
2015-01-01
Boophilus tick is a bloodsucking ectoparasite that transfers some pathogens, reducing production and thus leading to economical losses in the cattle industry. Tropomyosin (TPM) protein is a salivary protein, has actin regulator activity, and plays an important role in immune reactions against parasites. In the current study, besides developing a safe, effective, and broad spectrum protective measure against Boophilus genus tick based on TPM protein, we attempted to minimize possible problems occurring in the design of polytopic vaccines. Briefly, the steps that were followed in the present study were as follows: retrieving sequences and finding the mutational/conservative regions, selecting consensus and high immunogenic epitopes of B and CD4(+) T cells by different approaches, three-dimensional structure (3D structure) prediction and representation of epitopes and highly variable/conserve regions, designing vaccinal construct by fusion of B and T cell epitopes by special patterns and improving immunogenicity, evaluation of the constructs' primary structure and posttranslational modification, calculation of hydrophobic regions, reverse translation, codon optimization, open reading frame checking, insertion of start/end codon, Kozak sequence, and finally constructing the DNA vaccine. Variation plot showed some shared epitopes among the ticks' and mites' species that some might be effective only in some species. Finally, by following the steps mentioned above, two constructs for B and T cells were achieved. Checking constructs revealed their reliability and efficacy for in vitro production and utilization. Successful in silico modeling is an essential step of designing vigorous vaccines. We developed a novel protective and therapeutic vaccine against Boophilus genus (based on TPM protein). At the next step, constructed DNA vaccine would be produced in vitro and administrated to cattle, and its potency to induction of immune response and protection against Boophilus
A Systematic Review of Pliance, Tracking, and Augmenting
Kissi, Ama; Hughes, Sean; Mertens, Gaëtan; Barnes-Holmes, Dermot; De Houwer, Jan; Crombez, Geert
Within relational frame theory, a distinction has been made between three types of rule-governed behavior known as pliance, tracking, and augmenting. This review examined whether there is support for the concepts of pliance, tracking, and augmenting in the experimental analysis of behavior; whether
Introduction to Mobile Augmented Reality Development in Unity
Directory of Open Access Journals (Sweden)
Jacob W. Greene
2016-07-01
Full Text Available This lesson serves as an introduction to creating mobile augmented reality applications. Augmented reality (AR can be defined as the overlaying of digital content (images, video, text, sound, etc. onto physical objects or locations, and it is typically experienced by looking through the camera lens of an electronic device such as a smartphone, tablet, or optical head-mounted display (e.g. Microsoft Hololens. Although AR is a cutting-edge, complex technology, there are a number of user-friendly platforms that allow people with no previous coding experience to create compelling augmented reality experiences.
Gunner Goggles: Implementing Augmented Reality into Medical Education.
Wang, Leo L; Wu, Hao-Hua; Bilici, Nadir; Tenney-Soeiro, Rebecca
2016-01-01
There is evidence that both smartphone and tablet integration into medical education has been lacking. At the same time, there is a niche for augmented reality (AR) to improve this process through the enhancement of textbook learning. Gunner Goggles is an attempt to enhance textbook learning in shelf exam preparatory review with augmented reality. Here we describe our initial prototype and detail the process by which augmented reality was implemented into our textbook through Layar. We describe the unique functionalities of our textbook pages upon augmented reality implementation, which includes links, videos and 3D figures, and surveyed 24 third year medical students for their impression of the technology. Upon demonstrating an initial prototype textbook chapter, 100% (24/24) of students felt that augmented reality improved the quality of our textbook chapter as a learning tool. Of these students, 92% (22/24) agreed that their shelf exam review was inadequate and 19/24 (79%) felt that a completed Gunner Goggles product would have been a viable alternative to their shelf exam review. Thus, while students report interest in the integration of AR into medical education test prep, future investigation into how the use of AR can improve performance on exams is warranted.
Efficacy, Immunogenicity and Safety of a Human Rotavirus Vaccine RIX4414 in Singaporean Infants.
Phua, Kong Boo; Lim, Fong Seng; Quak, Seng Hock; Lee, Bee Wah; Teoh, Yee Leong; Suryakiran, Pemmaraju V; Han, Htay Htay; Bock, Hans L
2016-02-01
This was the first study conducted to evaluate the efficacy of 2 oral doses of the human rotavirus vaccine, RIX4414 in Singaporean infants during the first 3 years of life. Healthy infants, 11 to 17 weeks of age were enrolled in this randomised (1:1), double-blinded, placebo-controlled study to receive 2 oral doses of RIX4414 vaccine/placebo following a 0-, 1-month schedule. Vaccine efficacy against severe rotavirus (RV) gastroenteritis (Vesikari score ≥11) caused by wild-type RV strains from a period starting from 2 weeks post-Dose 2 until 2 and 3 years of age was calculated with 95% confidence interval (CI). Immunogenicity and safety of the vaccine were also assessed. Of 6542 infants enrolled, 6466 were included in the efficacy analysis and a subset of 100 infants was included in the immunogenicity analysis. Fewer severe RV gastroenteritis episodes were reported in the RIX4414 group when compared to placebo at both 2 and 3 year follow-up periods. Vaccine efficacy against severe RV gastroenteritis at the respective time points were 93.8% (95% CI, 59.9 to 99.9) and 95.2% (95% CI, 70.5 to 99.9). One to 2 months post-Dose 2 of RIX4414, 97.5% (95% CI, 86.8 to 99.9) of infants seroconverted for anti-RV IgA antibodies. The number of serious adverse events recorded from Dose 1 until 3 years of age was similar in both groups. Two oral doses of RIX4414 vaccine was immunogenic and provided high level of protection against severe RV gastroenteritis in Singaporean children, during the first 3 years of life when the disease burden is highest.
Immunogenicity to Biotherapeutics – the role of Anti-drug Immune complexes
Directory of Open Access Journals (Sweden)
Murli eKrishna
2016-02-01
Full Text Available AbstractBiologic molecules are increasingly becoming a part of the therapeutics portfolio that has been either recently approved for marketing or those that are in the pipeline of several biotech and pharmaceutical companies. This is largely based on their ability to be highly specific relative to small molecules. However by virtue of being a large protein, and having a complex structure with structural variability arising from production using recombinant gene technology in cell lines, such therapeutics run the risk of being recognized as foreign by a host immune system. Given the range of immune mediated adverse effects that have been documented to biologic drugs thus far, including infusion reactions, and the evolving therapeutic platforms in the pipeline that engineer different functional modules in a biotherapeutic, it is critical to understand the interplay of the adaptive and innate immune responses, the pathophysiology of immunogenicity to biologic drugs in instances where there have been immune mediated adverse clinical sequelae and address technical approaches for their laboratory evaluation. The current paradigm in immunogenicity evaluation has a tiered approach to the detection and characterization of anti-drug antibodies (ADAs elicited in vivo to a biotherapeutic; alongside with the structural, biophysical and molecular information of the therapeutic, these analytical assessments form the core of the immunogenicity risk assessment. However many of the immune mediated adverse effects attributed to ADAs require the formation of a drug/ADA immune complex intermediate (ICs that can have a variety of downstream effects. This review will focus on the activation of potential immunopathological pathways arising as a consequence of circulating as well as cell surface bound drug bearing-ICs, risk factors that are either intrinsic to the therapeutic molecule or to the host which might predispose to IC mediated effects, and review the recent
Immunogenicity, protective efficacy and mechanism of novel CCS adjuvanted influenza vaccine.
Even-Or, Orli; Samira, Sarit; Rochlin, Eli; Balasingam, Shobana; Mann, Alex J; Lambkin-Williams, Rob; Spira, Jack; Goldwaser, Itzhak; Ellis, Ronald; Barenholz, Yechezkel
2010-09-07
We optimized the immunogenicity of adjuvanted seasonal influenza vaccine based on commercial split influenza virus as an antigen (hemagglutinin = HA) and on a novel polycationic liposome as a potent adjuvant and efficient antigen carrier (CCS/C-HA vaccine). The vaccine was characterized physicochemically, and the mechanism of action of CCS/C as antigen carrier and adjuvant was studied. The optimized CCS/C-HA split virus vaccine, when administered intramuscularly (i.m.), is significantly more immunogenic in mice, rats and ferrets than split virus HA vaccine alone, and it provides for protective immunity in ferrets and mice against live virus challenge that exceeds the degree of efficacy of the split virus vaccine. Similar adjuvant effects of optimized CCS/C are also observed in mice for H1N1 swine influenza antigen. The CCS/C-HA vaccine enhances immune responses via the Th1 and Th2 pathways, and it increases both the humoral responses and the production of IL-2 and IFN-γ but not of the pro-inflammatory factor TNFα. In mice, levels of CD4(+) and CD8(+) T-cells and of MHC II and CD40 co-stimulatory molecules are also elevated. Structure-function relationship studies of the CCS molecule as an adjuvant/carrier show that replacing the saturated palmitoyl acyl chain with the mono-unsaturated oleoyl (C18:1) chain affects neither size distribution and zeta potential nor immune responses in mice. However, replacing the polyalkylamine head group spermine (having two secondary amines) with spermidine (having only one secondary amine) reduces the enhancement of the immune response by ∼ 50%, while polyalkylamines by themselves are ineffective in improving the immunogenicity over the commercial HA vaccine. This highlights the importance of the particulate nature of the carrier and the polyalkylamine secondary amines in the enhancement of the immune responses against seasonal influenza. Altogether, our results suggest that the CCS/C polycationic liposomes combine the
Augmentative biological control of arthropods in Latin America
Lenteren, van J.C.; Bueno, V.H.P.
2003-01-01
Augmentative forms of biological control, where natural enemies are periodically introduced, are applied over large areas in various cropping systems in Latin America. About 25% of the world area under augmentative control is situated in this region. Well-known examples are the use of species of the
Augmented reality mobile application for overlaying images on textiles
Brinza, Veronica
2016-01-01
Augmented reality is one the relatively new and fast growing branches in modern informatics. It incorporates in simple people lives on a lot of different levels. It can be used everywhere starting from the simple checking of your email and ending up with a complex augmented reality video games or augmented reality learning. From the ancient times actors tried to immerse the spectators in world of the performance using decoration and costumed. In XVIII – XIX centuries pictures w...
Augmented reality tools and learning practice in mobile-learning
Figueiredo, Mauro; Gomes, José; Gomes, Cristina; Lopes, João
2014-01-01
There are many augmented reality (AR) applications available that can be used to create educational contents for these mobile devices. This paper surveys the most popular augmented reality applications and we select AR eco-systems to be used in daily teaching activities which are user friendly, do not require programming skills and are free. Different augmented reality technologies are explored in this paper to create teaching activities with animations, videos and other information to be sho...
Augmented reality aiding collimator exchange at the LHC
International Nuclear Information System (INIS)
Martínez, Héctor; Fabry, Thomas; Laukkanen, Seppo; Mattila, Jouni; Tabourot, Laurent
2014-01-01
Novel Augmented Reality techniques have the potential to have a large positive impact on the way remote maintenance operations are carried out in hazardous areas, e.g. areas where radiation doses that imply careful planning and optimization of maintenance operations are present. This paper describes an Augmented Reality strategy, system and implementation for aiding the remote collimator exchange in the LHC, currently the world's largest and highest-energy particle accelerator. The proposed system relies on marker detection and multi-modal augmentation in real-time. A database system has been used to ensure flexibility. The system has been tested in a mock-up facility, showing real time performance and great potential for future use in the LHC. The technical-scientific difficulties identified during the development of the system and the proposed solutions described in this paper may help the development of future Augmented Reality systems for remote handling in scientific facilities
Augmented reality aiding collimator exchange at the LHC
Energy Technology Data Exchange (ETDEWEB)
Martínez, Héctor, E-mail: hector.martinez@sensetrix.com [SenseTrix, PL 20 FI-00101 Helsinki (Finland); Fabry, Thomas [European Organization for Nuclear Research, CERN, CH-1211 Genève 23 (Switzerland); Laukkanen, Seppo [SenseTrix, PL 20 FI-00101 Helsinki (Finland); Mattila, Jouni [Tampere University of Technology, PO Box 527, FI-33101 Tampere (Finland); Tabourot, Laurent [SYMME, Université de Savoie, Polytech Annecy-Chambéry, 5 chemin de Bellevue, 74944 Annecy le Vieux (France)
2014-11-01
Novel Augmented Reality techniques have the potential to have a large positive impact on the way remote maintenance operations are carried out in hazardous areas, e.g. areas where radiation doses that imply careful planning and optimization of maintenance operations are present. This paper describes an Augmented Reality strategy, system and implementation for aiding the remote collimator exchange in the LHC, currently the world's largest and highest-energy particle accelerator. The proposed system relies on marker detection and multi-modal augmentation in real-time. A database system has been used to ensure flexibility. The system has been tested in a mock-up facility, showing real time performance and great potential for future use in the LHC. The technical-scientific difficulties identified during the development of the system and the proposed solutions described in this paper may help the development of future Augmented Reality systems for remote handling in scientific facilities.
Transaxillary Endoscopic Breast Augmentation
Directory of Open Access Journals (Sweden)
Hyung-Bo Sim
2014-09-01
Full Text Available The axillary technique is the most popular approach to breast augmentation among Korean women. Transaxillary breast augmentation is now conducted with sharp electrocautery dissection under direct endoscopic vision throughout the entire process. The aims of this method are clear: both a bloodless pocket and a sharp non-traumatic dissection. Round textured or anatomical cohesive gel implants have been used to make predictable well-defined inframammary creases because textured surface implants demonstrated a better stability attributable to tissue adherence compared with smooth surface implants. The axillary endoscopic technique has greatly evolved, and now the surgical results are comparable to those with the inframammary approach. The author feels that this technique is an excellent choice for young patients with an indistinct or absent inframammary fold, who do not want a scar in the aesthetic unit of their chest.
Govindarajan, Dhanasekaran; Kim, Shin-Hee; Samal, Siba K
2010-03-01
Avian metapneumovirus (AMPV) causes an upper respiratory tract infection in turkeys leading to serious economic losses to the turkey industry. The G glycoprotein of AMPV is known to be associated with viral attachment and pathogenesis. In this study, we determined the role of the G glycoprotein in the pathogenicity and immunogenicity of AMPV strain Colorado (AMPV/CO). Recombinant AMPV/CO lacking the G protein (rAMPV/CO-deltaG) was generated using a reverse-genetics system. The recovered rAMPV/CO-deltaG replicated slightly better than did wild-type AMPV in Vero cells. However, deletion of the G gene in AMPV resulted in attenuation of the virus in turkeys. The mutant virus induced less-severe clinical signs and a weaker immune response in turkeys than did the wild-type AMPV. Our results suggest that the G glycoprotein is an important determinant for the pathogenicity and immunogenicity of AMPV.