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DNA Vaccination (dna + vaccination)

Distribution by Scientific Domains

Medical Sciences	47%
Life Sciences	38%

Selected Abstracts

Polymeric Materials for Gene Delivery and DNA Vaccination

ADVANCED MATERIALS, Issue 8 2009
David N. Nguyen
Abstract Gene delivery holds great potential for the treatment of many different diseases. Vaccination with DNA holds particular promise, and may provide a solution to many technical challenges that hinder traditional vaccine systems including rapid development and production and induction of robust cell-mediated immune responses. However, few candidate DNA vaccines have progressed past preclinical development and none have been approved for human use. This Review focuses on the recent progress and challenges facing materials design for nonviral DNA vaccine drug delivery systems. In particular, we highlight work on new polymeric materials and their effects on protective immune activation, gene delivery, and current efforts to optimize polymeric delivery systems for DNA vaccination. [source]

Activation drives PD-1 expression during vaccine-specific proliferation and following lentiviral infection in macaques

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2008
David
Abstract Recent data supports that increased expression of PD-1, a negative regulator of immune function, is associated with T cell exhaustion during chronic viral infection. However, PD-1 expression during acute infection and vaccination has not been studied in great detail in primates. Here, we examine PD-1 expression on CD3+ T cells following DNA vaccination or lentiviral infection of macaques. Ex vivo peptide stimulation of PBMC from DNA-vaccinated uninfected macaques revealed a temporal increase in PD-1 expression in proliferating antigen-specific CD8+ T cells. Following the initial increase, PD-1 expression steadily declined as proliferation continued, with a concomitant increase in IFN-, secretion. Subsequent examination of PD-1 expression on T cells from uninfected and lentivirus-infected non-vaccinated macaques revealed a significant increase in PD-1 expression with lentiviral infection, consistent with previous reports. PD-1 expression was highest on cells with activated memory and effector phenotypes. Despite their decreased telomere length, PD-1hi T cell populations do not appear to have statistically significant uncapped telomeres, typically indicative of proliferative exhaustion, suggesting a different mechanistic regulation of proliferation by PD-1. Our data indicate that PD-1 expression is increased as a result of T cell activation during a primary immune response as well as during persistent immune activation in macaques. Supporting Information for this article is available at www.wiley-vch.de/contents/jc_2040/2008/37857_s.pdf [source]

Incomplete effector/memory differentiation of antigen-primed CD8+ T,cells in gene gun DNA-vaccinated mice

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2003
Christina Bartholdy
Abstract DNA vaccination is an efficient way to induce CD8+ T,cell memory, but it is still unclear to what extent such memory responses afford protection in vivo. To study this, we induced CD8+ memory responses directed towards defined viral epitopes, using DNA vaccines encoding immunodominant MHC class,I-restricted epitopes of lymphocytic choriomeningitis virus covalently linked to ,2-microglobulin. This vaccine construct primed for a stronger recall response than did a more conventional minigene construct. Despite this, vaccinated mice were only protected against systemic infection whereas protection against the consequences of peripheral challenge was limited. Phenotypic analysis revealed that DNA vaccine-primed CD8+ T,cells in uninfected mice differed from virus-primed CD8+ T,cells particularly regarding expression of very-late antigen (VLA)-4, an adhesion molecule important for targeting T,cells to inflammatory sites. Thus, our DNA vaccine induces a long-lived memory CD8+ T,cell population that provides efficient protection against high-dose systemic infection. However, viral replication in solid non-lymphoid organs is not curtailed sufficiently fast to prevent significant virus-induced inflammation. Our results suggest that this is due to qualitative limitations of the primed CD8+ T,cells. [source]

Enhancement of protective humoral immune responses against Herpes simplex virus-2 in DNA-immunized guinea-pigs using protein boosting

FEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2008
Fatemeh Fotouhi
Abstract Genital Herpes is a common sexually transmitted disease that is caused mostly by Herpes simplex virus type 2 (HSV-2). Its prevalence has increased in developing countries in spite of the availability of valuable antiviral drug therapy. Considering the importance of HSV-2 infections, effective vaccines remain the most likely hope for controlling the spread of HSV diseases. In the present study, the complete HSV-2 glycoprotein D gene was isolated and cloned into different plasmid vectors to construct a DNA vaccine and prepare recombinant subunit vaccines using a baculovirus expression system. The vaccines were tested alone or in combination to evaluate their ability to induce protective immunity in guinea-pigs against genital HSV infections. Immunization elicited humoral responses as measured by neutralization tests and enzyme-linked immunosorbent assay, and immunized animals had less severe genital skin disease as well as reduced replication of the challenging virus in the genital tract during experimental infection. Our results further demonstrate that DNA priming-protein boosting induced a neutralizing antibody titer higher than that obtained with DNA,DNA vaccination. The massive increase of antibody titer following DNA priming-protein boosting might be attributed to a recall of B cell memory. [source]

Induction or expansion of T-cell responses by a hepatitis B DNA vaccine administered to chronic HBV carriers

HEPATOLOGY, Issue 4 2004
Maryline Mancini-Bourgine
Despite the availability of effective hepatitis B vaccines for many years, over 370 million people remain persistently infected with hepatitis B virus (HBV). Viral persistence is thought to be related to poor HBV-specific T-cell responses. A phase I clinical trial was performed in chronic HBV carriers to investigate whether HBV DNA vaccination could restore T-cell responsiveness. Ten patients with chronic active hepatitis B nonresponder to approved treatments for HBV infection were given 4 intramuscular injections of 1 mg of a DNA vaccine encoding HBV envelope proteins. HBV-specific T-cell responses were assessed by proliferation, ELISpot assays, and tetramer staining. Secondary end points included safety and the monitoring of HBV viraemia and serological markers. Proliferative responses to hepatitis B surface antigen were detected in two patients after DNA injections. Few HBV-specific interferon ,,secreting T cells were detectable before immunization, but the frequency of such responses was significantly increased by 3 DNA injections. Immunization was well tolerated. Serum HBV DNA levels decreased in 5 patients after 3 vaccine injections, and complete clearance was observed in 1 patient. In conclusion, this study provides evidence that HBV DNA vaccination is safe and immunologically effective. We demonstrate that DNA vaccination can specifically but transiently activate T-cell responses in some chronic HBV carriers who do not respond to current antiviral therapies. Supplementary material for this article can be found on the HEPATOLOGYwebsite (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (HEPATOLOGY 2004;40:874,882.) [source]

Cross-presentation, dendritic cell subsets, and the generation of immunity to cellular antigens

IMMUNOLOGICAL REVIEWS, Issue 1 2004
William R. Heath
Summary:, Cross-presentation involves the uptake and processing of exogenous antigens within the major histocompatibility complex (MHC) class I pathway. This process is primarily performed by dendritic cells (DCs), which are not a single cell type but may be divided into several distinct subsets. Those expressing CD8, together with CD205, found primarily in the T-cell areas of the spleen and lymph nodes, are the major subset responsible for cross-presenting cellular antigens. This ability is likely to be important for the generation of cytotoxic T-cell immunity to a variety of antigens, particularly those associated with viral infection, tumorigenesis, and DNA vaccination. At present, it is unclear whether the CD8,-expressing DC subset captures antigen directly from target cells or obtains it indirectly from intermediary DCs that traffic from peripheral sites. In this review, we examine the molecular basis for cross-presentation, discuss the role of DC subsets, and examine the contribution of this process to immunity, with some emphasis on DNA vaccination. [source]

Induction of a protective capsular polysaccharide antibody response to a multiepitope DNA vaccine encoding a peptide mimic of meningococcal serogroup C capsular polysaccharide

IMMUNOLOGY, Issue 2 2003
Deborah M. Prinz
Summary Systemic infection by encapsulated organisms, such as Neisseria meningitidis, is a major cause of morbidity and mortality worldwide, especially in individuals less than 2 years of age. Antibodies directed at the capsular polysaccharide are shown to be protective against disease by inducing complement-dependent bactericidal activity. The current polysaccharide vaccine has been shown to be poorly immunogenic in high-risk groups and this is probably related to its T-independent properties. An alternative approach to eliciting a T-dependent serum immunoglobulin G (IgG) antibody response to encapsulated pathogens is DNA vaccination. We assessed the immunogenicity of a multiepitope DNA vaccine encoding a T-cell helper epitope and a peptide mimic of N. meningitidis serogroup C. The DNA construct induced a significant anti-polysaccharide antibody response that was bactericidal. Mice immunized with the DNA construct were subsequently protected against challenge with a lethal dose of N. meningitidis serogroup C. [source]

Polymeric Materials for Gene Delivery and DNA Vaccination

Enhanced efficacy of DNA vaccination against Her-2/neu tumor antigen by genetic adjuvants

INTERNATIONAL JOURNAL OF CANCER, Issue 1 2004
Sun Young Chang
Abstract Certain types of malignant tumors overexpress Her-2/neu, a transmembrane glycoprotein of the class I receptor tyrosine kinase erbB family. To develop an effective Her-2/neu vaccine for selective immunotherapy of these malignancies, we prepared Her-2/neu DNA plasmid encoding the transmembrane and extracellular domain (pHM) and tested the ability of this construct to induce antitumor immunity in animal models. In addition, we investigated the effects of cytokine used as a genetic adjuvant. Modulation by factors that affect T-cell function or hematopoiesis, including interleukin-12, interleukin-15, interleukin-18, interleukin-23, Eta-1, Flt3L and GM-CSF, was studied in the forms of monocistronic and bicistronic plasmid. Our results demonstrated that vaccination of pHM could induce successful antitumor immunity against Her-2/neu-expressing murine tumor cells in BALB/c mice. We also showed that the antitumor activity of pHM was augmented by coadministration and coexpression of different cytokines. Despite the similar levels of gene expression, the antitumor effects of bicistronic plasmids coexpressing Her-2/neu antigen and cytokine were improved in comparison with coadministration of separate monocistronic plasmid. In particular, coexpression of interleukin-18 or GM-CSF with Her-2/neu increased antitumor activity in both preventive and therapeutic experiments. These findings can help in the decision concerning which of the various cytokine adjuvants should be used for the development of a Her-2/neu DNA vaccine. In addition, our results from a large panel of cytokine adjuvants in the various tumor models may provide an insight into the important immune components of antitumor immunity. © 2004 Wiley-Liss, Inc. [source]

Mucosal challenge of Macaca nemestrina with simian immunodeficiency virus (SIV) following SIV nucleocapsid mutant DNA vaccination*

JOURNAL OF MEDICAL PRIMATOLOGY, Issue 3-4 2000
Robert J. Gorelick
A simian immunodeficiency virus (SIV)(Mne) DNA clone was constructed that produces viruses containing a four amino acid deletion in the second zinc finger of the nucleocapsid (NC) domain of the Gag polyprotein. Viruses produced from this clone, although non-infectious both in vitro and in vivo, complete a majority of the steps in a single retroviral infection cycle. Eight pig-tailed macaques (Macaca nemestrina) were inoculated intramuscularly and subcutaneously three times over the course of 24 weeks with the NC mutant expressing DNA. These macaques, and four controls, were then challenged mucosally (intrarectally) with the homologous virus (SIV Mne CL E11S) and monitored for evidence of infection and clinical disease. Prior to challenge, a measurable humoral immune response was noted in four of eight immunized macaques. After challenge, all 12 macaques became infected, although four immunized animals greatly restricted their viral replication, and one immunized animal that controlled replication remains antibody negative. No disease has been evidence during the 46-week period of monitoring after challenge. [source]

Enhancing effects of the chemical adjuvant levamisole on the DNA vaccine pVIR-P12A-IL18-3C

MICROBIOLOGY AND IMMUNOLOGY, Issue 9 2008
Lu Huijun
ABSTRACT DNA-based vaccination is an attractive alternative for overcoming the disadvantages of inactivated virus vaccines; however, DNA vaccines alone often generate only weak immune responses. In this study, the efficacy of LMS as a chemical adjuvant on a DNA vaccine (pVIR-P12A-IL18-3C) encoding the P1-2A and 3C genes of the FMDV and swine IL-18, which provides protection against FMDV challenge, was tested. All test pigs were administered booster vaccinations 28 days after the initial inoculation, and were challenged with 1000 ID50 FMDV O/NY00 20 days after the booster vaccination. Positive and negative control groups were inoculated with inactivated virus vaccine and PBS respectively. The DNA vaccine plus LMS induced greater humoral and cell-mediated responses than the DNA vaccine alone, as evidenced by higher concentrations of neutralizing and specific anti-FMDV antibodies, and by higher concentrations of T-lymphocyte proliferation and IFN-, production, respectively. FMDV challenge revealed that the DNA vaccine plus LMS provided higher protection than the DNA vaccine alone. This study demonstrates that LMS may be useful as an adjuvant for improving the protective efficiency of DNA vaccination against FMDV in pigs. [source]

CD40-expressing plasmid induces anti-CD40 antibody and enhances immune responses to DNA vaccination

THE JOURNAL OF GENE MEDICINE, Issue 1 2010
Hanqian Xu
Abstract Background Various approaches have been used to improve the efficacy of DNA vaccination, including the incorporation of molecular adjuvants. Because the CD40 ligand,CD40 interaction plays a major role in initiating immune responses, we sought to develop a molecular adjuvant targeting this interaction. Methods and Results We immunized mice with a foot-and-mouth disease virus DNA vaccine, pcD-VP1, together with a CD40-expressing plasmid, pcD-CD40. We found that pcD-CD40 induced anti-CD40 antibodies, which temporally correlated with the augmented production of anti-VP1 antibody. pcD-CD40 similarly augmented the humoral response of another DNA vaccine that targets hepatitis B virus, and passive transfer of anti-CD40 antisera also showed a similar effect. Furthermore, the pcD-CD40-elicited anti-CD40 antibodies were able to activate the CD40 signal pathway in antigen-presenting cells in vitro, which led to the maturation of dendritic cells (DCs) and DC-mediated T cell activation. Thus, pcD-CD40 augments DNA vaccination by inducing anti-CD40 antibodies, which in turn promotes T cell activation. Conclusions This is the first reported ,proadjuvant' that augments DNA vaccination indirectly by eliciting agonistic antibodies. Copyright © 2009 John Wiley & Sons, Ltd. [source]

FK506 as an adjuvant of tolerogenic DNA vaccination for the prevention of experimental autoimmune encephalomyelitis

THE JOURNAL OF GENE MEDICINE, Issue 11 2009
Youmin Kang
Abstract Background DNA vaccination is a strategy that has been developed primarily to elicit protective immunity against infection and cancer. Methods DNA vaccine was used, in conjunction with an immunosuppressant, to tolerize harmful autoimmunity. Results Immunization of C57BL/6 mice with MOG35,55, a myelin oligodendrocyte glycoprotein-derived peptide, and FK506 (Tacrolimus) as a tolerogenic adjuvant stimulated regulatory dendritic cells, induced antigen-specific regulatory T cells (Treg), and protected the animals from subsequent induction of experimental autoimmune encephalomyelitis (EAE). After EAE induction, there were fewer lymphocytes, including fewer T helper 17 cells, and more Treg infiltrating the spinal cord in the immunized mice compared to in control mice. Furthermore, at the peak of the EAE manifestation, CD4 T cells in the immunized mice showed decreased expression of interferon-, and interleukin (IL)-17, but not IL-4, in treated mice. Conclusions DNA vaccination, when applied with an immunosuppressant as adjuvant, can induce antigen-specific tolerance and prevent autoimmune disease. Copyright © 2009 John Wiley & Sons, Ltd. [source]

DNA vaccination against foot-and-mouth disease via electroporation: study of molecular approaches for enhancing VP1 antigenicity

THE JOURNAL OF GENE MEDICINE, Issue 9 2006
Suk-Am Kim
Abstract Background Foot-and-mouth disease virus (FMDV) affects susceptible livestock animals and causes disastrous economic impact. Immunization with plasmid expressing VP1 that contains the major antigenic epitope(s) of FMDV as cytoplasmic protein (cVP1) failed to elicit full protection against FMDV challenge. Materials and methods In this study, mice were immunized via electroporation with four cDNA expression vectors that were constructed to express VP1 of FMDV, as cytoplasmic (cVP1), secreted (sVP1), membrane-anchored (mVP1) or capsid precursor protein (P1), respectively, to evaluate whether expression of VP1 in specific subcellular compartment(s) would result in better immune responses. Results Electroporation enhanced immune responses to vectors expressing cVP1 or P1 and expedited the immune responses to vectors expressing sVP1 or mVP1. Immunization of mice via electroporation with mVP1 cDNA was better than sVP1 or cVP1 cDNA in eliciting neutralizing antibodies and viral clearance protection. Vaccination with P1 cDNA, nonetheless, yielded the best immune responses and protection among all four cDNAs that we tested. Conclusions These results suggest that the antigenicity of a VP1 DNA vaccine can be significantly enhanced by altering the cellular localization of the VP1 antigen. Electroporation is a useful tool for enhancing the immune responses of vectors expressing VP1 or P1. By mimicking FMDV more closely than that of transgenic VP1 and eliciting immune responses favorably toward Th2, transgenic P1 may induce more neutralizing antibodies and better protection against FMDV challenge. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Early events of electroporation-mediated intramuscular DNA vaccination potentiate Th1-directed immune responses

THE JOURNAL OF GENE MEDICINE, Issue 9 2005
Eirik Grønevik
Abstract Background Application of electrical pulses after DNA injection into muscle increases expression of the encoded genes, and is shown to improve antigen-specific immune responses when used for DNA vaccination. In addition, electroporation causes tissue injury and inflammatory reactions. Together with immune stimulatory motifs in the injected DNA these factors may potentiate the immune response by acting as adjuvants for the antigen. Here, we have examined the role of these factors in promoting the efficiency of DNA vaccination. Methods We injected a plasmid DNA vector containing the gene Ag85B from M. tuberculosis into mouse quadriceps muscles followed by electroporation. Ag85B was under control of a Tet-responsive promoter, and was expressed either immediately or up to 28 days later by administrating doxycycline to the mice. Delayed expression was combined with injection of non-coding DNA or saline with or without electroporation to examine the ability of these factors to enhance the Ag85B-specific antibody response in the blood and cellular responses in the spleen. Blood samples were analysed with ELISA, while the number of Ag85B-specific IFN-,- and IL-4-producing spleenocytes was analysed with ELISpot. Results Delaying Ag85B expression by 5 or 28 days caused lower anti-Ag85B-specific IgG2a levels. In contrast, the IgG1 antibody response was not significantly affected. Injection of non-coding DNA followed by electroporation moderately increased the IgG2a response. Delaying the Ag85B expression by 28 days reduced the average number of Ag85B-specific IFN-,-producing spleenocytes by over 60%. No significant change in the number of IL-4-producing Ag85B-specific spleenocytes was observed. Conclusions These results suggest that DNA and electroporation per se may act as good adjuvants in promoting efficient Th1-directed responses during DNA vaccination. Copyright © 2005 John Wiley & Sons, Ltd. [source]

DNA vaccination against tumors

THE JOURNAL OF GENE MEDICINE, Issue 1 2005
Gérald J. Prud'homme
Abstract DNA vaccines have been used to generate protective immunity against tumors in a variety of experimental models. The favorite target antigens have been those that are frequently expressed by human tumors, such as carcinoembryonic antigen (CEA), ErbB2/neu, and melanoma-associated antigens. DNA vaccines have the advantage of being simple to construct, produce and deliver. They can activate all arms of the immune system, and allow substantial flexibility in modifying the type of immune response generated through codelivery of cytokine genes. DNA vaccines can be applied by intramuscular, dermal/epidermal, oral, respiratory and other routes, and pose relatively few safety concerns. Compared to other nucleic acid vectors, they are usually devoid of viral or bacterial antigens and can be designed to deliver only the target tumor antigen(s). This is likely to be important when priming a response against weak tumor antigens. DNA vaccines have been more effective in rodents than in larger mammals or humans. However, a large number of methods that might be applied clinically have been shown to ameliorate these vaccines. This includes in vivo electroporation, and/or inclusion of various immunostimulatory molecules, xenoantigens (or their epitopes), antigen-cytokine fusion genes, agents that improve antigen uptake or presentation, and molecules that activate innate immunity mechanisms. In addition, CpG motifs carried by plasmids can overcome the negative effects of regulatory T cells. There have been few studies in humans, but recent clinical trials suggest that plasmid/virus, or plasmid/antigen-adjuvant, prime-boost strategies generate strong immune responses, and confirm the usefulness of plasmid-based vaccination. Copyright © 2004 John Wiley & Sons, Ltd. [source]

Immune response of DNA vaccine against lymphocystis disease virus and expression analysis of immune-related genes after vaccination

AQUACULTURE RESEARCH, Issue 10 2010
Feng Rong Zheng
Abstract In this study, we found that an intramuscular injection of Japanese flounder (Paralichthys olivaceus, 60,80 g in weight and 15,20 mL in length) with 5 ,g of a DNA vaccine (pEGFP-N2-LCDV-cn-MCP 0.6 kb, containing lymphocystis disease virus major capsid protein gene) induced a strong immune response. Subsequent real-time polymerase chain reaction showed that the expression of immune-related genes [e.g., major histocompatibility complex (MHC) class I ,, MHC II ,, T-cell receptor (TCR), tumour necrosis factor (TNF), tumour necrosis factor receptor (TNFR), Mx, interleukin (IL)-1,, CXC and IL-8R] was significantly changed after DNA vaccination. The most remarkable alternation was the expression of MHC I , and MHC II , genes: MHC II , reached the maximum on day 8 in different tissues, and MHC I , on day 2 in the intestine and gills. The expression of TCR increased and reached a plateau in 2 days in the spleen, gills, kidney and liver after vaccination and then decreased after day 8. In contrast, the expression of TCR in the intestine increased and reached a plateau in 8 days. The expression of IL-8R reached the maximum on day 2 in different tissues and then decreased on day 8. Mx increased in the gills, kidney, spleen and liver on days 2, 8, 2 and 2, but decreased in the intestine, gills, spleen and liver on days 2, 8, 8 and 8 respectively. The TNFR expression increased in the spleen, kidney and gills on days 2, 8 and 8, but decreased in intestine, liver and gills on days 2, 8 and 8 respectively. The expression of TNF, CXC and IL-1, increased 2 and 8 days after the injection of DNA vaccine. However, the expression of TNF, CXC and IL-1, altered on days 2 and 8 with different patterns in different tissues respectively. The fish responded to the DNA vaccine by yielding a specific immunoglobulin against lymphocystis disease virus (LCDV) as observed with indirect ELISA. The DNA vaccine induced a unique humoral response, suggesting that the DNA vaccine activated both cellular and humoral defences of the specific immune system of Japanese flounder. [source]

DNA VACCINES AND ALLERGIC DISEASES

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2006
Kaw Yan Chua
SUMMARY 1Allergic diseases are characterized by inappropriate immune responses to common environmental antigens. The prevalence of these diseases has been increasing worldwide for reasons that are not exactly clear. 2Current treatment is largely symptomatic. Because the initial observation that simple plasmid DNA injections resulted in in vivo protein expression and induction of adaptive immune responses to the encoded antigen, the potential of modifying the allergic immune responses by DNA vaccination so as to treat and prevent these diseases has been explored extensively. 3In the present paper we review preclinical studies using animal models of allergic diseases, with an emphasis on DNA vaccine design, for house dust mite allergens-related allergic asthma. [source]