Dennis Thompson, HealthDay News An experimental DNA-based vaccine protected monkeys from infection with the Zika virus, and it has proceeded to human safety trials, researchers report.
Our previous studies have shown that therapeutic DNA vaccine induction of mucosal responses correlated with significant reduction of virus in the gut of SIV-inf...
TY - JOUR. T1 - Enhancing DNA vaccine potency by combining a strategy to prolong dendritic cell life and intracellular targeting strategies with a strategy to boost CD4+ T cell. AU - Kim, Daejin. AU - Hoory, Talia. AU - Wu, T. C.. AU - Hung, Chien Fu. PY - 2007/11/1. Y1 - 2007/11/1. N2 - Intradermal administration of DNA vaccines, using a gene gun, represents an effective means of delivering DNA directly into professional antigen-presenting cells (APCs) in the skin and thus allows the application of strategies to modify the properties of APCs to enhance DNA vaccine potency. In the current study, we hypothesized that the potency of human papillomavirus (HPV) type 16 E7 DNA vaccines employing intracellular targeting strategies combined with a strategy to prolong the life of dendritic cells (DCs) could be further enhanced by the addition of a DNA vaccine capable of generating high numbers of pan-HLA-DR reactive epitope (PADRE)-specific CD4+ T cells. We observed that the addition of PADRE DNA to E7 ...
Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials
Due to their rapid and widespread development, DNA vaccines have entered into a variety of human clinical trials for vaccines against various diseases including cancer. Evidence that DNA vaccines are well tolerated and have an excellent safety profile proved to be of advantage as many clinical trials combines the first phase with the second, saving both time and money. It is clear from the results obtained in clinical trials that such DNA vaccines require much improvement in antigen expression and delivery methods to make them sufficiently effective in the clinic. Similarly, it is clear that additional strategies are required to activate effective immunity against poorly immunogenic tumor antigens. Engineering vaccine design for manipulating antigen presentation and processing pathways is one of the most important aspects that can be easily handled in the DNA vaccine technology. Several approaches have been investigated including DNA vaccine engineering, co-delivery of immunomodulatory molecules, safe
DNA vaccines have progressed rapidly from the conceptual stage to the stage of clinical trials. While studies in small laboratory animals have shown great promise, initial reports from human studies were less encouraging. Progress is being made, however, documented by the papers presented here. This volume contains the proceedings of a meeting devoted to the latest developments in DNA vaccines, from laboratory studies to clinical trials. The papers, written by leaders in the field, focus on the current state of DNA vaccines in humans and other large animals. The bulk of the studies involve DNA vaccines against HIV/SIV. Other promising trials make use of DNA vaccines against malaria and hepatitis B. The papers inform the reader about the immune basis of this form of vaccination and about approaches being developed to increase the efficacy of DNA vaccines in humans. These include the co-administration of cytokines, prime-boost strategies, optimising codon usage or the use of CpG motifs. An ...
This topic contains 2 study abstracts on Vaccination: Plasmid DNA Vaccines indicating they may negatively impact Infertility, Vaccination: Abortion, and Vaccine-induced Toxicity
In addition to the general medical benefits, DNA vaccines can provide a large economic benefit. Due to the decreased restrictions in the production and storage of DNA vaccines compared to regular vaccines, the cost of producing and maintaining DNA vaccines is much lower. This can be especially beneficial to people in developing countries. According to certain case studies, the cost of developing and manufacturing a successful and beneficial conventional vaccine can range from $500 million to $1 billion. Comparatively, the development and manufacturing of a DNA vaccine ranges between $200 and $300 million ...
A novel DNA vaccine vector encoding the Mycobacterium tuberculosis secreted antigen Ag85A fused with the influenza A virus (IAV) HA2 protein epitopes, pEGFP/Ag85A-sHA2 (pAg85A-sHA2), was designed to provide protection against influenza. The antigen encoded by the DNA vaccine vector was efficiently expressed in mammalian cells, as determined by reverse transcription polymerase chain reaction (RT-PCR) and fluorescence analyses. Mice were immunized with the vaccine vector by intramuscular injection before challenge with A/Puerto Rico/8/34 virus (PR8 virus). Sera and the splenocyte culture IFN-γ levels were significantly higher in immunized mice compared with the control mice. The novel vaccine group showed a high neutralization antibody titer in vitro. The novel vaccine vector also reduced the viral loads, increased the survival rates in mice after the PR8 virus challenge and reduced the alveolar inflammatory cell numbers. Sera IL-4 concentrations were significantly increased in mice immunized with the
Nucleic acid vaccines, like other biotechnology derived vaccines, will be evaluated on a case-by-case basis. Evaluation of vaccine master seeds is an essential first step for fulfilling these requirements.
T. gondii is an important zoonotic Apicomplexan parasite, but no drugs could eliminate the pathogen from the host effectively. In recent studies, DNA vaccines have shown the potential to defend against T. gondii infection in view of their abilities to induce long-term humoral and cellular immune responses in animal models. Many rhoptry proteins (ROP5, ROP13, ROP16 and ROP18) [16-19] are identified to be potential candidates for development of T. gondii DNA vaccines. TgROP38, a new member of the rhoptry protein family, was firstly identified by the phylogenomic approach and was found to regulate the expression of host transcription factors, signaling pathways and cell proliferation, and apoptosis that sum up about 1200 host genes [21]. These key biological roles of TgROP38 in T. gondii infection of the host have stimulated us to evaluate whether TgROP38 could elicit effective immune responses against infection with T. gondii in the mice model. Therefore, we constructed the recombinant plasmid ...
The spleens of intramuscularly or gene gun immunized mice enlarged notably compared with those of the unimmunized controls. In particular, the spleen weight of the gene gun injected mice almost doubled that of the unimmunized controls (data not shown). FACS analysis of spleen cells harvested 2 weeks after the final immunization with AMA-1 or AMA-1 plus IL-12 DNA vaccines showed notable differences in the proportions of CD4+ and CD8+ T-lymphocytes between the intramuscular injection versus the gene gun (epidermis) injection (Fig. 2). In mice immunized intramuscularly (n=5 for each group) with AMA-1 alone or AMA-1 plus IL-12 DNA vaccines, the proportions of T-cell subsets (17.9±0.47% or 15.5±0.79% for CD8+ T-cells and 27.6±0.84% or 27.7±0.72% for CD4+ T-cells) did not show any significant changes (P,0.05), compared with control mice immunized only with UB vector (16.2±0.78% for CD8+ T-cells and 26.5±0.35% for CD4+ T-cells) (Fig. 2). By contrast, in mice injected with a gene gun (n=3 for each ...
The effectiveness of a vaccine may be increased when combined with an adjuvant and/or when given with EP. The addition of an adjuvant or EP may increase a persons immune response to a vaccine. Furthermore, the immune response to HIV antigens may be improved by giving a DNA vaccine boosted with a live vector vaccine. The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of an HIV DNA vaccine (HIV-MAG) alone or in combination with an IL-12 pDNA adjuvant, delivered IM via EP followed by a Vesicular Stomatitis Virus (VSV) HIV gag vaccine boost given IM by needle and syringe in healthy, HIV-uninfected adults.. Participants will be enrolled into the study in one of four groups. Each of the four groups will receive 3 mg of the HIV-MAG vaccine alone or combined with one of three different doses of the IL-12 pDNA adjuvant, followed by the VSV HIV gag vaccine boost. Within each of the four groups, participants will be randomly assigned to receive the study vaccines or ...
The effectiveness of a vaccine may be increased when combined with an adjuvant and/or when given with EP. The addition of an adjuvant or EP may increase a persons immune response to a vaccine. Furthermore, the immune response to HIV antigens may be improved by giving a DNA vaccine boosted with a live vector vaccine. The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of an HIV DNA vaccine (HIV-MAG) alone or in combination with an IL-12 pDNA adjuvant, delivered IM via EP followed by a Vesicular Stomatitis Virus (VSV) HIV gag vaccine boost given IM by needle and syringe in healthy, HIV-uninfected adults.. Participants will be enrolled into the study in one of four groups. Each of the four groups will receive 3 mg of the HIV-MAG vaccine alone or combined with one of three different doses of the IL-12 pDNA adjuvant, followed by the VSV HIV gag vaccine boost. Within each of the four groups, participants will be randomly assigned to receive the study vaccines or ...
DNA vaccination is a technique for protecting against disease by injection with genetically engineered DNA so cells directly produce an antigen, producing a protective immunological response. DNA vaccines have potential advantages over conventional vaccines, including the ability to induce a wider range of immune response types. Several DNA vaccines are available for veterinary use. Currently no DNA vaccines have been approved for human use. Research is investigating the approach for viral, bacterial and parasitic diseases in humans, as well as for several cancers. Vaccines have eliminated naturally occurring smallpox, and nearly eliminated polio, while other diseases, such as typhus, rotavirus, hepatitis A and B and others are well controlled. Conventional vaccines cover a small number of diseases, while other infections kill millions of people every year. First generation vaccines are whole-organism vaccines - either live and weakened, or killed forms. Live, attenuated vaccines, such as ...
To further improve fertility of animals, a novel gene RFRP-3 (RF-amide related peptide-3,RFRP-3) was used to construct DNA vaccines with INH α (1-32) (inhibin, IN...
Scientists have developed a novel method for delivering therapeutic molecules into cells. The method harnesses gold nanoparticles that are electrically activated, causing them to oscillate and bore holes in cells outer membranes and allowing key molecules - such as DNA, RNA, and proteins - to gain entry.
Abstract Autophagy plays an important role in neoplastic transformation of cells and in resistance of cancer cells to radio and chemotherapy. p62 (SQSTM1) is a key component of autophagic machinery which is also involved in signal transduction. Although recent empirical observations demonstrated that p62 is overexpressed in variety of human tumors, a mechanism of p62 overexpression is not known. Here we report that the transformation of normal human mammary epithelial cells with diverse oncogenes (RAS, PIK3CA and Her2) causes marked accumulation of p62. Based on this result, we hypothesized that p62 may be a feasible candidate to be an anti- cancer DNA vaccine. Here we performed a preclinical study of a novel DNA vaccine encoding p62. Intramuscularly administered p62-encoding plasmid induced anti-p62 antibodies and exhibited strong antitumor activity in three models of allogeneic mouse tumors - B16 melanoma, Lewis lung carcinoma (LLC), and S37 sarcoma. P62-encoding plasmid has demonstrated its ...
In this work, we report the evaluation of two DNA vaccines against dengue-3 virus (DENV-3). The first construction, called pVAC3DEN3, was engineered inserting the pre-membrane (prM) and envelope (E) gene of DENV-3 truncated with a restriction site between them, as previously described. The second construction was developed cloning the full gene sequence of prM and E from DENV-3 virus in pCI plasmid for mammalian expression and was denominated pVAC1WDEN3. The results showed that both constructions were capable of expressing the prM and E proteins, as demonstrated by ELISA and immunoblotting detection in cell culture transfected with the plasmids. After positive
PowderMed Ltd. (a subsidiary of Pfizer) was developing a therapeutic DNA vaccine for the treatment of genital warts caused by the human papillomavirus (HPV).
With increasing prophylactic HPV vaccination rates among the general population and the expansion of FDA approval for vaccination of all age groups, the rates of HPV infection and subsequent malignancy are set to drop over the coming decades.3 27 There remains, however, an unmet need for an HPV therapeutic vaccine. Currently, there are over 10 HPV therapeutic vaccines under development, and in various stages of clinical testing, but mostly in phase I or II.11 Vaccines are being developed employing multiple platforms, including DNA, bacterial and viral vectors, peptides and proteins. VGX-3100 is an HPV 16/18 DNA-based vaccine that is administered intramuscularly via electroporation, and is currently being tested in a phase III trial (NCT03721978) for high-grade cervical lesions, CIN2/3, which are a direct precursor to cervical cancer. AXAL-CERV is a Listeria monocytogenes-based vaccine currently in a phase III clinical trial to treat patients with high risk locally advanced cervical cancer (NCT ...
Influenza is one of the most important illnesses in the modern world, causing great public health losses each year due to the lack of medication and broadly protective, long-lasting vaccines. The development of highly immunogenic and safe vaccines is currently one of the major problems encountered in efficient influenza prevention. DNA vaccines represent a novel and powerful alternative to the conventional vaccine approaches. To improve the efficacy of the DNA vaccine against influenza H5N1, we inserted three repeated kappa B (κB) motifs, separated by a 5-bp nucleotide spacer, upstream of the cytomegalovirus promoter and downstream of the SV40 late polyadenylation signal. The κB motif is a specific DNA element (10pb-long) recognized by one of the most important transcription factors NFκB. NFκB is present in almost all animal cell types and upon cell stimulation under a variety of pathogenic conditions. NFκB is released from IκB and translocates to the nucleus and binds to κB sites, ...
DNA vaccines promote an immune response by providing antigen-encoding DNA to the recipient, but the efficacy of such vaccines needs improving. Many approaches have considerable potential but currently induce relatively weak immune responses despite multiple high doses of DNA vaccine. Here, we asked whether targeting vaccine antigens to DCs would increase the immunity and protection that result from DNA vaccines. To determine this, we generated a DNA vaccine encoding a fusion protein comprised of the vaccine antigen and a single-chain Fv antibody (scFv) specific for the DC-restricted antigen-uptake receptor DEC205. Following vaccination of mice, the vaccine antigen was expressed selectively by DCs, which were required for the increased efficacy of MHC class I and MHC class II antigen presentation relative to a control scFv DNA vaccine. In addition, a DNA vaccine encoding an HIV gag p41-scFv DEC205 fusion protein induced 10-fold higher antibody levels and increased numbers of IFN-γ-producing CD4+ ...
Researchers at the Johns Hopkins Bloomberg School of Public Health and Emory developed a DNA vaccine proven to protect against measles, the most conclusive evidence yet that DNA vaccines may be useful in the fight against human disease.
A novel synthetic DNA vaccine can, for the first time, induce protective immunity against the Middle East Respiratory Syndrome (MERS) coronavirus in animal species, reported researchers from the Perelman School of Medicine at the University of Pennsylvania.
Speaker: Honorary Doctor of Karolinska Institutet Margaret A. Liu Host: Francesca Chiodi Dr Margaret A. Liu has been appointed Honorary Doctor of Karolinska Institutet; she is honored for her frontline research and education within the field of DNA-based vaccines. Margaret Liu is the President of the International Society of Vaccines, the founder of ProTherImmune and she is affiliated with University of California, San Francisco, and Karolinska Institutet
Straus compared dl5-29 with a glycoprotein vaccine previously tested in humans and a third vaccine comprising a naked circular strand of DNA encoding the glycoprotein. Naked DNA vaccines have generated interest in recent years for their potential to elicit a stronger cellular immune response than by simply injecting the protein. Straus said that he tested dl5-29 against "the best tested standard vaccine plus the competing new concept in the field, DNA vaccines," in order to get a better sense of how well the dl 5-29 vaccine performed. His team tested the vaccines both in mice and in guinea pigs. The latter is the best model of human HSV-2 disease because it is the only one that mimics many of the aspects of the human disease, such as a recurring infection interspersed with periods of latency. The researchers studied how well the vaccines worked prophylactically-to prevent infection-and therapeutically to help control an existing infection ...
Health,Swedish researchers have expressed hope regarding the DNA vaccine tria...DNA vaccines represent the latest innovation in the area of vaccin...The technology is highly promising for producing simple inexpens...Although the study is not yet over the researchers are very posit...The second phase trial targeted at testing the effectiveness of t...,DNA,Vaccine,Trials,Against,HIV,Virus,In,Sweden,Nurture,Hope,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news
Vical Incorporated (Nasdaq VICL) announced today that the company s Vaxfectin adjuvant has significantly boosted the immune response of DNA-based vaccines again
Researchers have made significant progress in the development of a potential vaccine to protect against HIV infection. For the first time, researchers have shown that a combined approach - using a common cold virus to introduce a vaccine into the body, as well as an injection of a DNA-based vaccine - results in the immune system actively protecting against HIV in the gut and bodily cavities.
Our data demonstrate that a single dose of a DNA vaccine or a purified inactivated virus vaccine provides complete protection against the ZIKV challenge in mice, said senior author Dan H. Barouch, MD, PhD, Director of the Center for Virology and Vaccine Research at BIDMC, Professor of Medicine at Harvard Medical School, and Steering Committee member at the Ragon Institute of MGH, MIT and Harvard. Importantly, we showed that vaccine-induced antibodies provided protection, similar to existing vaccines for other flaviviruses. The researchers tested two vaccine candidates: a DNA vaccine developed in the Barouch laboratory at BIDMC, and a purified inactivated virus vaccine developed at WRAIR. The DNA vaccine used gene sequences from a ZIKV strain from Brazil to elicit immune responses. Four weeks following vaccination, mice were exposed to the Brazilian strain of ZIKV, which had previously been shown to cause defects in fetal mice similar to those observed in ZIKV infected humans. All vaccinated ...
A research paper has been published on the three potential Zika virus vaccines that are being tested in humans at present. Two are based on cutting-edge DNA vaccine technology and the third is based on the more standard inactivated virus model.. The DNA vaccines under development interfere with the virus ability to enter cells and replicate itself, while the inactivated vaccine aims to create an immune response that would provide future protection against Zika.. Of the three, a DNA vaccine developed by the US National Institutes of Health has progressed the furthest, with a large multi-site phase 2 trial underway involving almost 2500 test subject.. Stephen Thomas, one of the authors of the paper, said research and development has been incredibly brisk and that some groundbreaking strides have been made in very short periods of time.. The paper states: The development of a safe and effective vaccine is an urgent global health priority. Promising data from preclinical vaccine studies in ...
The attenuated live M. bovis Bacille-Calmette-Guérin (BCG) is still the sole vaccine used against tuberculosis, but confers only variable efficacy against adult pulmonary tuberculosis (TB). Though no clear explanation for this limited efficacy has been given, different hypotheses have been advanced, such as the waning of memory T-cell responses, a reduced antigenic repertoire and the inability to induce effective CD8+ T-cell responses, which are known to be essential for latent tuberculosis control. In this study, a new BCG-based vaccination protocol was studied, in which BCG was formulated in combination with a plasmid DNA vaccine. As BCG is routinely administered to neonates, we have evaluated a more realistic approach of a simultaneous intradermal coadministration of BCG with pDNA encoding the prototype antigen, PPE44. Strongly increased T- and B-cell responses were observed with this protocol in C57BL/6 mice when compared to the administration of only BCG or in combination with an empty pDNA
Inovio Pharmaceuticals is developing VGX 3100, a SynCon® therapeutic DNA vaccine for the treatment of high-grade HPV-caused pre-cancers and other related
This guidance describes our current recommendations concerning preclinical development and testing of DNA vaccines to prevent infectious diseases. This guidance supercedes the 1996 …
the prime-boost and DNA vaccine approaches induced significant protection in hamsters, as well as a specific IgG antibody response and sterilising immunity. Although vaccination with recombinant fragment of LigBrep also produced a strong antibody response, it was not immunoprotective. These results highlight the potential of LigBrep as a candidate antigen for an effective vaccine against leptospirosis and emphasise the use of the DNA prime-protein boost as an important strategy for vaccine development ...
Evaluation of Immunogenicity of Cocktail DNA Vaccine Contain¬ing Plasmids Encoding Complete GRA5, SAG1, and ROP2 Antigens of Toxoplasma gondii in BALB/C Mice
[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.] J Infect Dis. 2019 Mar 19. pii: jiz132. doi: 10.1093/infdis/jiz132. [Epub ahead of print] Intradermal SynCon® Ebola GP DNA Vaccine is Temperature Stable and Safely Demonstrates Cellular and Humoral Immunogenicity Advantages in Healthy Volunteers. Tebas P1, Kraynyak KA2, Patel A3, Maslow JN4, Morrow MP2, Sylvester AJ2, Knoblock D2, Gillespie E2, Amante D2, Racine T5, McMullan…
Zothecula writes Taking a two-month-old in for vaccination shots and watching them get stuck with six needles in rapid succession can be painful for child and parent alike. If the work of an MIT team of researchers pans out, those needles may be thing of the past thanks to a new dissolvable polymer...
DNA immunization, also known as gene immunization, polynucleotide vaccine and DNA vaccine, is a newly established immunological theory and technique first discovered in the 1990s. Compared with current protein vaccine, DNA immunization is safer and more inexpensive. Besides, it induces a more effective immune response and is easy to be prepared. With the potential application in some specific field, DNA immunization is not only been widely used in anti-virus, bacteria, fungi, parasites as well as other anti-infection immunity, but also plays a n important role in tumor immunology and autoimmune disease. Like all other groups, Creative Biolabs follows up with the updated technique in DNA immunization, and made their own innovation by putting DNA immunization in the production of antibody. ...
Marking an important step in the development of immunotherapy cancer treatment, scientists have demonstrated that nanoparticle-coated bacteria can effectively deliver an oral DNA vaccine that stimulates the bodys own immune ...
Cui, Tingting et al. Construction of an artificial recombinant bicistronic plasmid DNA vaccine against porcine rotavirus. Onderstepoort j. vet. res., 2013, vol.80, no.1, p.1-8. ISSN 0030- ...
The interleukin (IL)-13 receptor alpha2 (IL-13Ralpha2) chain is a primary binding and internalization subunit for a Th2-derived immune regulatory cytokine, IL-13. Although extremely high levels of IL-13Ralpha2 chain are expressed on a variety of human tumor cells and specimens, its precise role in tumor immunology has not been defined. To investigate the role of IL-13Ralpha2 in tumor immunity, we used D5 melanoma cells stably transfected with the human IL-13Ralpha2 gene (D5alpha2) to assess the effect of an IL-13Ralpha2 DNA vaccine in immunocompetent animals. Prophylactic immunization of mice with the IL-13Ralpha2 DNA vaccine resulted in protection against D5alpha2 tumor development. In vivo depletion experiments in C57BL/6 and RAG-2 knockout mice indicated that both T and B cells, but not natural killer cells, were required for the tumor protection. In addition, antibody induced by the IL-13Ralpha2 DNA vaccine showed a modest but significant inhibitory effect on D5alpha2 cells in vitro, ...
New and increasingly sophisticated vaccines are taking aim at a broad range of disease-causing pathogens, targeting them with greater effectiveness at lower cost and with improved measures to ensure safety.
Researchers at BRIC, the University of Copenhagen, have discovered that the human body can create its own vaccine, which boosts the immune system and helps prevent chronic inflammatory diseases.
DNA vaccination is an active immunointervention procedure to induce a protective immunological response by injection with genetically engineered DNA coding for
Biotech begins clinical manufacturing; expects to test Zika vaccine in humans in 2016 PLYMOUTH MEETING, Pa., Feb. 17, 2016 (GLOBE NEWSWIRE) -- Inovio Pharmaceuticals, Inc. (NASDAQ:INO) announced...
The Herpevac Trial for Women revealed that three dose HSV-2 gD vaccine was 58% protective against culture-positive HSV-1 genital disease, but it was not protective against HSV-2 infection or disease. To determine whether vaccine-induced immune responses had selected for a particular gD sequence in strains infecting vaccine recipients compared with viruses infecting control subjects, genetic sequencing studies were carried out on viruses isolated from subjects infected with HSV-1 or HSV-2. We identified naturally occurring variants among the gD sequences obtained from 83 infected subjects. Unique or low frequency amino acid substitutions in the ectodomain of gD were found in 6 of 39 HSV-1-infected subjects and in 7 of 44 HSV-2-infected subjects. However, no consistent amino acid change was identified in isolates from gD-2 vaccine recipients compared with infected placebo recipients. gC and gE surround and partially shield gD from neutralizing antibody, and gB also participates closely in the viral entry
Immune response in mice immunized with IgM-D4/SV40 DNA vaccine.(A) Antibody analyses of IgG subclass after immunization with IgM-D4/SV40 DNA vaccine using EP de
Vical Incorporated today announced that in a recently completed animal study, a DNA vaccine formulated with the company s patented Vaxfectin(TM) adjuvant and de