| human adenovirus type 35 vector for gene therapy of brain cancer: improved transduction and bypass of pre-existing anti-vector immunity in cancer patients. | clinical trials in malignant glioma have demonstrated excellent safety of recombinant adenovirus type 5 (ad5) but lack of convincing efficacy. the overall low expression levels of the coxsackie and adenovirus receptor and the presence of high anti-ad5-neutralizing antibody (nab) titers in the human population are considered detrimental for consistency of clinical results. to identify an adenoviral vector better suited to infect primary glioma cells, we tested a library of fiber-chimeric ad5-base ... | 2007 | 17082793 |
| the short consensus repeats 1 and 2, not the cytoplasmic domain, of human cd46 are crucial for infection of subgroup b adenovirus serotype 35. | human cd46 (membrane cofactor protein) has recently been identified to be an attachment receptor for subgroup b adenoviruses (ads); however, the precise interaction between human cd46 and subgroup b ads are just beginning to be understood. in this study, to characterize the interaction between human cd46 and subgroup b ads, varieties of mutant cd46 were tested for their ability to act as a receptor for ad serotype 35 (ad35), which belongs to subgroup b. in addition, we determined ad35 vector-med ... | 2006 | 16790289 |
| detection of cell cycle- and differentiation stage-dependent human telomerase reverse transcriptase expression in single living cancer cells. | elevated telomerase activity is an important molecular signature of cancer cells and primitive cells in regenerative tissues. however, isolation of single living cells with endogenous telomerase activity has not yet been possible. here, we developed adenovirus serotype 35 tropism-based vectors encoding destabilized enhanced green fluorescence protein with a half-life of 2 h (d2egfp) driven by the human telomerase reverse transcriptase (htert) promoter. as assessed in telomerase-positive or -nega ... | 2006 | 16584924 |
| priming with an adenovirus 35-circumsporozoite protein (cs) vaccine followed by rts,s/as01b boosting significantly improves immunogenicity to plasmodium falciparum cs compared to that with either malaria vaccine alone. | the rts,s/as02a protein-based vaccine consistently demonstrates significant protection against infection with plasmodium falciparum malaria and also against clinical malaria and severe disease in children in areas of endemicity. here we demonstrate with rhesus macaques that priming with a replication-defective human adenovirus serotype 35 (ad35) vector encoding circumsporozoite protein (cs) (ad35.cs), followed by boosting with rts,s in an improved mpl- and qs21-based adjuvant formulation, as01b, ... | 2007 | 17307942 |
| immunogenicity and protection of a recombinant human adenovirus serotype 35-based malaria vaccine against plasmodium yoelii in mice. | given the promise of recombinant adenovirus type 5 (rad5) as a malaria vaccine carrier in preclinical models, we evaluated the potency of rad35 coding for plasmodium yoelii circumsporozoite protein (rad35pycs). we chose rad35 since a survey with serum samples from african subjects demonstrated that human ad35 has a much lower seroprevalence of 20% and a much lower geometric mean neutralizing antibody titer (gmt) of 48 compared to ad5 (seroprevalence, 85%; gmt, 1,261) in countries with a high mal ... | 2006 | 16368986 |
| broad cellular immunity with robust memory responses to simian immunodeficiency virus following serial vaccination with adenovirus 5- and 35-based vectors. | adenovirus serotype 35 (ad35) is a promising vaccine platform for human immunodeficiency virus (hiv) infection and emerging infectious diseases as it is uncommon in humans worldwide and is distinct from ad5, the major vaccine serotype for which many individuals have pre-existing immunity. the immunogenicity of a first-generation, replication-competent ad35-based vaccine was tested in the simian immunodeficiency virus (siv) rhesus macaque model by evaluating its capacity to boost immunity generat ... | 2006 | 16361426 |
| immunogenicity of recombinant fiber-chimeric adenovirus serotype 35 vector-based vaccines in mice and rhesus monkeys. | preexisting immunity to adenovirus serotype 5 (ad5) has been shown to suppress the immunogenicity of recombinant ad5 (rad5) vector-based vaccines for human immunodeficiency virus type 1 (hiv-1) in both preclinical studies and clinical trials. a potential solution to this problem is to utilize rad vectors derived from rare ad serotypes, such as ad35. however, rad35 vectors have appeared less immunogenic than rad5 vectors in preclinical studies to date. in this study, we explore the hypothesis tha ... | 2005 | 16254351 |
| the distal short consensus repeats 1 and 2 of the membrane cofactor protein cd46 and their distance from the cell membrane determine productive entry of species b adenovirus serotype 35. | the human regulator of complement activation membrane cofactor protein (cd46) has recently been identified as an attachment receptor for most species b adenoviruses (ads), including ad type 3 (ad3), ad11, and ad35, as well as species d ad37. to characterize the interaction between ad35 and cd46, hybrid receptors composed of different cd46 short consensus repeat (scr) domains fused to immunoglobulin-like domains of cd4 and a set of 36 cd46 mutants containing semiconservative changes of single ami ... | 2005 | 16014961 |
| downregulation of human cd46 by adenovirus serotype 35 vectors. | human cd46 (membrane cofactor protein), which serves as a receptor for a variety of pathogens, including strains of measles virus, human herpesvirus type 6 and neisseria, is rapidly downregulated from the cell surface following infection by these pathogens. here, we report that replication-incompetent adenovirus (ad) serotype 35 (ad35) vectors, which belong to subgroup b and recognize human cd46 as a receptor, downregulate cd46 following infection. a decline in the surface expression of cd46 in ... | 2007 | 17377598 |
| macropinocytotic uptake and infection of human epithelial cells with species b2 adenovirus type 35. | human adenovirus serotype 35 (hadv-35; here referred to as ad35) causes kidney and urinary tract infections and infects respiratory organs of immunocompromised individuals. unlike other adenoviruses, ad35 has a low seroprevalence, which makes ad35-based vectors promising candidates for gene therapy. ad35 utilizes cd46 and integrins as receptors for infection of epithelial and hematopoietic cells. here we show that infectious entry of ad35 into hela cells, human kidney hk-2 cells, and normal huma ... | 2010 | 20237079 |
| adenovirus serotype 35 vector-mediated transduction into human cd46-transgenic mice. | we previously demonstrated that systemic administration of adenovirus serotype 35 (ad35) vectors to mice does not mediate efficient transduction in organs, probably because expression of the mouse analog of the subgroup b ad receptor, human cd46 (membrane cofactor protein), is limited to the testis. here, we describe the in vitro and in vivo transduction characteristics of ad35 vectors by using homozygous and hemizygous human cd46-transgenic (cd46tg) mice, which ubiquitously express human cd46. ... | 2006 | 16541121 |
| localization of regions in cd46 that interact with adenovirus. | a variety of pathogens use cd46, a ubiquitously expressed membrane protein that regulates complement activation, as a cellular attachment receptor. while the cd46 binding sites of several pathogens, including measles virus, neisseria gonorrhea, and human herpesvirus 6, have been described, the region of cd46 responsible for adenovirus binding has not been determined. in this study, we used competition experiments with known cd46 ligands, cd46-specific antibodies, and a set of cd46 mutants to loc ... | 2005 | 15919905 |
| [characterization of adenovirus serotype 35 vectors using genetically modified animals and non-human primates]. | recombinant adenovirus (ad) vectors are considered to be a promising gene delivery vehicle of high utility because they are easy to construct, can be produced at high titers, and efficiently transduce various types of cells. ad vectors commonly used in the world, including clinical trials, are composed of ad serotype 5 (ad5), which belongs to subgroup c. in recent years, however, it has become apparent that ad5 vectors have some drawbacks, such as high seroprevalence of anti-ad5 antibodies in ad ... | 2006 | 17077607 |
| optimization of adenovirus serotype 35 vectors for efficient transduction in human hematopoietic progenitors: comparison of promoter activities. | adenoviral gene transfer to hematopoietic stem cells (hscs)/progenitors would provide a new approach to the treatment of hematopoietic diseases and study of the hematopoietic system. we have previously reported that an adenovirus (ad) vector composed of whole ad serotype 35 (ad35), which belongs to subgroup b, shows efficient gene transfer into human bone marrow cd34+ cells. however, ad35 vector-mediated transduction into human hscs/progenitors has not yet been fully optimized. in the present st ... | 2005 | 15944730 |
| adenovirus serotype 35 vector-induced innate immune responses in dendritic cells derived from wild-type and human cd46-transgenic mice: comparison with a fiber-substituted ad vector containing fiber proteins of ad serotype 35. | recently, much attention has focused on replication-incompetent adenovirus (ad) vectors containing fiber proteins derived from species b ad serotype 35 (ad35) (ad5f35) and ad vectors fully constructed from ad35 as vaccine vectors expressing antigens. however, differences in the transduction properties, including the induction of innate immunity, of ad5f35 and ad35 vectors have not been properly and fully examined, partly because the transduction properties of these ad vectors should be evaluated ... | 2010 | 20800630 |
| towards an rts,s-based, multi-stage, multi-antigen vaccine against falciparum malaria: progress at the walter reed army institute of research. | the goal of the malaria vaccine program at the walter reed army institute of research (wrair) is to develop a licensed multi-antigen, multi-stage vaccine against plasmodium falciparum able to prevent all symptomatic manifestations of malaria by preventing parasitemia. a secondary goal is to limit disease in vaccinees that do develop malaria. malaria prevention will be achieved by inducing humoral and cellular immunity against the pre-erythrocytic circumsporozoite protein (csp) and the liver stag ... | 2005 | 15755604 |
| characterization of in vitro and in vivo gene transfer properties of adenovirus serotype 35 vector. | we have recently developed a replication-defective, recombinant adenovirus (ad) vector composed of the whole ad serotype 35 (ad35), a member of subgroup b. we describe herein the in vitro and in vivo gene transfer properties of ad35 vector in comparison with ad serotype 5 (ad5) and the ad5f35 vector, which is a fiber-substituted ad5 vector containing ad35 fiber proteins. in vitro, ad35 vector efficiently transduced not only human car-positive cells but also car-negative cells. following intraven ... | 2003 | 14599815 |
| acute adenoviral infection of a graft by serotype 35 following renal transplantation. | adenoviral infections of immunocompetent patients usually present as self-limiting pharyngitis, gastroenteritis, urocystitis, or conjunctivitis. in immunosuppressed patients, development of the illness can be severe, even life-threatening or fatal, and therapeutical intervention is difficult. previous case reports of adenoviral infections after kidney transplantation have described a symptomatology of hemorrhagic cystitis, fever, renal dysfunction, and rarely fatal systemic dissemination. here w ... | 2003 | 14533942 |
| an adenoviral type 5 vector carrying a type 35 fiber as a vaccine vehicle: dc targeting, cross neutralization, and immunogenicity. | substituting the coat proteins of adenoviral vector serotype 5 (ad5) can alter vector tropism and circumvent vector neutralization. here we report that an ad5 vector carrying a part of the fiber molecule of human subgroup b adenovirus serotype 35 (ad5.fib35) transduces cultured human dendritic cells (dc) and circulating myeloid derived dc with approximately 10-fold greater efficiency than ad5 in vitro. the improved dc transduction results in increased t-cell activation ex vivo. in vivo however, ... | 2004 | 15297053 |
| replication-deficient human adenovirus type 35 vectors for gene transfer and vaccination: efficient human cell infection and bypass of preexisting adenovirus immunity. | replication-deficient human adenovirus type 5 (ad5) can be produced to high titers in complementing cell lines, such as per.c6, and is widely used as a vaccine and gene therapy vector. however, preexisting immunity against ad5 hampers consistency of gene transfer, immunological responses, and vector-mediated toxicities. we report the identification of human ad35 as a virus with low global prevalence and the generation of an ad35 vector plasmid system for easy insertion of heterologous genes. in ... | 2003 | 12857895 |
| development of an adenoviral vector system with adenovirus serotype 35 tropism; efficient transient gene transfer into primary malignant hematopoietic cells. | a paucity of coxsackie adenovirus receptor (car) hampers the adenovirus serotype 5 (ad5)-based vector-mediated gene transfer into malignant hematopoietic cells. fiber-retargeted adenoviral vectors with species b tropism can potentially bypass the car requirement and facilitate efficient gene transfer into malignant hematopoietic cells. | 2004 | 15170734 |
| immunogenicity of recombinant adenovirus serotype 35 vaccine in the presence of pre-existing anti-ad5 immunity. | the high prevalence of pre-existing immunity to adenovirus serotype 5 (ad5) in human populations may substantially limit the immunogenicity and clinical utility of recombinant ad5 vector-based vaccines for hiv-1 and other pathogens. a potential solution to this problem is to use vaccine vectors derived from adenovirus (ad) serotypes that are rare in humans, such as ad35. however, cross-reactive immune responses between heterologous ad serotypes have been described and could prove a major limitat ... | 2004 | 15128818 |
| human adenovirus type 35: nucleotide sequence and vector development. | in this report, we describe the complete 34,794 base pair genomic sequence of the human adenovirus serotype 35 (ad35) holden strain. the viral genome exhibits a compact organization similar to other adenoviral serotypes, with overlapping genes on both strands. in all, 47 open reading frames (orfs) were identified, including early (e1, 2, 3, 4) and late (l1, 2, 3, 4, 5) regions conserved among the adenoviridae family. in addition, 14 orfs were identified that do not encode known adenoviral genes. ... | 2003 | 14528318 |
| development of adenovirus serotype 35 as a gene transfer vector. | while 51 human adenoviral serotypes have been identified to date, the vast majority of adenoviral vectors designed for gene transfer have been generated in the adenovirus serotype 5 (ad5) backbone. viral infections caused by ad5 are endemic in most human populations and the majority of humans carry preexisting humoral and/or cellular immunity to ad5 which may severely limit the use of ad5-based vectors for gene therapy applications. to circumvent this preexisting ad5 immunity, we have identified ... | 2003 | 12842627 |
| increased immunogenicity of recombinant ad35-based malaria vaccine through formulation with aluminium phosphate adjuvant. | previously, we have shown the potency of recombinant adenovirus serotype 35 viral vaccines (rad35) to induce strong immune response against the circumsporozoite protein (cs) of the plasmodium parasite. to further optimize immunogenicity of ad35-based malaria vaccines we formulated rad35.cs vaccine with aluminium phosphate adjuvant (alpo(4)). in contrast to the conventional protein based vaccines no absorption to aluminium adjuvant was observed and rad35 viral in vitro infectivity in mammalian ce ... | 2007 | 17646036 |
| targeting of adenovirus vectors to tumor cells does not enable efficient transduction of breast cancer metastases. | targeting of oncolytic adenoviruses to tumors can potentially increase their efficacy and safety profile after systemic application. we have developed recently a capsid-modified vector containing the adenovirus serotype 35 fiber shaft and knob inserted into an ad5 capsid. this ad5/35 vector infects cells via a coxsackievirus adenovirus receptor-independent pathway. here we attempted to exploit this new tropism of ad5/35 vectors for tumor-specific infection. in vitro, the ad5/35 vector efficientl ... | 2002 | 11861383 |
| impact of recombinant adenovirus serotype 35 priming versus boosting of a plasmodium falciparum protein: characterization of t- and b-cell responses to liver-stage antigen 1. | prime-boost vaccination regimens with heterologous antigen delivery systems have indicated that redirection of the immune response is feasible. we showed earlier that t-cell responses to circumsporozoite (cs) protein improved significantly when the protein is primed with recombinant adenovirus serotype 35 coding for cs (rad35.cs). the current study was designed to answer the question whether such an effect can be extended to liver-stage antigens (lsa) of plasmodium falciparum such as lsa-1. stud ... | 2008 | 18212075 |
| broad hiv epitope specificity and viral inhibition induced by multigenic hiv-1 adenovirus subtype 35 vector vaccine in healthy uninfected adults. | a correlation between in vivo and in vitro virus control mediated by cd8+ t-cell populations has been demonstrated by cd8 t-cell-mediated inhibition of hiv-1 and siv replication in vitro in peripheral blood mononuclear cells (pbmcs) from infected humans and non-human primates (nhps), respectively. here, the breadth and specificity of t-cell responses induced following vaccination with replication-defective adenovirus serotype 35 (ad35) vectors containing a fusion protein of gag, reverse transcri ... | 2014 | 24609066 |
| molecular cloning and physical mapping of the dna of human adenovirus type 35. | the prototype strain of the human adenovirus type 35 (av35) was examined. bamhi, ecori, hindiii, kpni, psti, and sali restriction endonucleases were used for the mapping of dna fragments. three original maps were constructed, and previously published maps were somewhat modified. a psti-specific fragment library was also prepared and characterized using the pbr322/e. coli system. some of the recombinants seem to be applicable for rapid dna diagnostics, and for the comparative mapping of type- and ... | 1989 | 2603646 |
| enhanced transduction efficiency of fiber-substituted adenovirus vectors by the incorporation of rgd peptides in two distinct regions of the adenovirus serotype 35 fiber knob. | fiber-substituted ad serotype 5 vectors containing the fiber protein from ad serotype 35 (ad5f35) exhibit properties that render them suitable as a platform for targeted ad vectors. ad5f35 vectors do not show apparent tropism in certain organs, including the liver, and they elicit less innate immunity than other vectors after intravenous administration. in order to develop a targeted ad vector, we previously developed fiber-mutant ad5f35 vectors containing the integrin binding arg-gly-asn (rgd) ... | 2011 | 20801174 |
| adenovirus serotype 35 vector-mediated transduction following direct administration into organs of nonhuman primates. | adenovirus (ad) serotype 35 (ad35) vectors have attracted remarkable attention as alternatives to conventional ad serotype 5 (ad5) vectors. in a previous study, we showed that intravenously administered ad35 vectors exhibited a safer profile than ad5 vectors in cynomolgus monkeys, which ubiquitously express cd46, an ad35 receptor, in a pattern similar to that in humans. however, the ad35 vectors poorly transduced the organs. in this study, we examined the transduction properties of ad35 vectors ... | 2009 | 18800152 |
| interaction of penton base arg-gly-asp motifs with integrins is crucial for adenovirus serotype 35 vector transduction in human hematopoietic cells. | most subgroup b adenoviruses (ads), including adenovirus (ad) serotype 35 (ad35), bind to human cd46 as a receptor; however, the infection processes of subgroup b ads following attachment to cd46 remain to be elucidated. subgroup b ads possess arg-gly-asp (rgd) motifs in the penton base, similarly to subgroup c ad serotypes 2 and 5. in this study, we examined the role of penton base rgd motifs in ad35 vector-mediated transduction in human hematopoietic cells. inhibition of interaction between in ... | 2007 | 17805302 |
| transduction properties of adenovirus serotype 35 vectors after intravenous administration into nonhuman primates. | adenovirus serotype 35 (ad35) vectors have shown promise as effective gene delivery vehicles. however, the transduction profiles of ad35 vectors in conventional mice allow only a limited estimation of transduction properties of these vectors, because the mouse analog of the subgroup b ad receptor, cd46, is restricted to the testis. in order to assess the transduction properties of ad35 vectors more completely, we performed transduction experiments using cynomolgus monkeys, which ubiquitously exp ... | 2008 | 18362928 |
| differential antigen requirements for protection against systemic and intranasal vaccinia virus challenges in mice. | the development of a subunit vaccine for smallpox represents a potential strategy to avoid the safety concerns associated with replication-competent vaccinia virus. preclinical studies to date with subunit smallpox vaccine candidates, however, have been limited by incomplete information regarding protective antigens and the requirement for multiple boost immunizations to afford protective immunity. here we explore the protective efficacy of replication-incompetent, recombinant adenovirus serotyp ... | 2008 | 18448519 |
| adenovirus 5- and 35-based immunotherapy enhances the strength but not breadth or quality of immunity during chronic siv infection. | heterologous adenovirus-based vectors hold promise as preventative hiv vaccines but their capacity to induce effective t-cell immunity in established infection has not been explored. we vaccinated rhesus macaques chronically infected with sivmac251 and undergoing antiretroviral therapy (art) with human adenovirus serotype 5-based vectors expressing siv gag, env, and nef with and without il-15 and evaluated vaccine immunogenicity. vaccination increased ag-specific t cells 20-fold but did not expa ... | 2009 | 19670380 |
| development and evaluation of a novel gene delivery vehicle composed of adenovirus serotype 35. | the capacity of gene delivery vehicles is considered to be a critical factor determining the success of gene therapy. to date, various types of gene delivery vehicle have been developed. among them, recombinant adeno-virus (ad) vectors have potential that has favored their worldwide use in vitro and in vivo. conventional ad vectors are composed of subgroup c ad serotype 5 (ad5), although it has been clarified that the drawbacks of ad5 vectors are a high seroprevalence of ad5 in adults and low tr ... | 2008 | 18827334 |
| [development of a replication-incompetent adenovirus vector derived from subgroup b adenovirus serotype 35]. | properties of gene delivery vehicles, including gene transfer efficiencies and toxicities, are a key parameter for successful gene therapy. among various types of gene delivery vehicles that have been developed so far, adenovirus (ad) vectors have promising potentials as a vector for gene therapy because they can easily be grown to high titers and can efficiently deliver genes to both dividing and non-dividing cells. however, recent studies demonstrated some drawbacks of conventional ad vectors, ... | 2008 | 19043294 |
| an efficient method for the delivery of the interleukin-2 gene to human hematopoietic cells using the
fiber-modified recombinant adenovirus. | recombinant human adenovirus serotype 5 (ad5/35f-il2) with modified fibres containing the c-terminal domain fiber-knob of human adenovirus serotype 35, carrying the gene of recombinant human il-2, has been designed. as a result of the fiber modification, the adenovirus can efficiently deliver the genetic information to bone marrow leukocytes and the tumor blood cells kg-1a (human myeloblastic leukemia cells) and u937 (human histiocytic lymphoma cells), which are normally resistant to ad5 infecti ... | 2011 | 22649700 |
| development of fiber-substituted adenovirus vectors containing foreign peptides in the adenovirus serotype 35 fiber knob. | fiber-substituted adenovirus (ad) vectors containing fibers of ad serotype 35 (adf35) efficiently transduce a variety of human cells because their receptor, human cd46, is ubiquitously expressed on almost all nucleated cells. however, the ubiquitous expression of cd46 might lead to unexpected transduction in untargeted organs. in this study, we developed fiber-modified adf35 vectors with an integrin-binding arg-gly-asn (rgd) peptide incorporated into the fg, hi or ij loop, which have been identi ... | 2009 | 19516278 |
| tumor-specific delivery of biologics by a novel t-cell line hozot. | "cell-in-cell" denotes an invasive phenotype in which one cell actively internalizes in another. the novel human t-cell line hozot, established from human umbilical cord blood, was shown to penetrate a variety of human cancer cells but not normal cells. oncolytic viruses are emerging as biological therapies for human cancers; however, efficient viral delivery is limited by a lack of tumor-specific homing and presence of pre-existing or therapy-induced neutralizing antibodies. here, we report a n ... | 2016 | 27901098 |
| safety and immunogenicity of a recombinant adenovirus serotype 35-vectored hiv-1 vaccine in adenovirus serotype 5 seronegative and seropositive individuals. | 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. | 2015 | 26587311 |
| the safety and immunogenicity of an adenovirus type 35-vectored tb vaccine in hiv-infected, bcg-vaccinated adults with cd4(+) t cell counts >350 cells/mm(3). | the safety and immunogenicity of a replication deficient adenovirus serotype 35 tuberculosis (tb) vaccine containing gene inserts for antigens (ag) 85a, ag85b and tb10.4 (aeras-402/ad35.tb-s) was evaluated in previously bcg vaccinated, hiv-infected south african adults with baseline cd4 counts >350 cells/mm(3). | 2015 | 25698492 |
| an alternative to the adenovirus inverted terminal repeat sequence increases the viral genome replication rate and provides a selective advantage in vitro. | during the development of human adenovirus 35-derived replication-incompetent (rad35) vaccine vectors for prevention of infectious diseases, we detected mutations in the terminal 8 nt of the inverted terminal repeats (itrs) of rad35. the switch from the plasmid-encoded sequence 5'-catcatca-3' to the alternative sequence 5'-ctatctat-3' in the itrs was found to be a general in vitro propagation phenomenon, as shown for several vectors carrying different transgenes or being derived from different a ... | 2014 | 24764357 |
| the effectiveness of the oncolytic activity induced by ad5/f35 adenoviral vector is dependent on the cumulative cellular conditions of survival and autophagy. | to overcome the poor tumor transduction efficiency of adenovirus serotype 5 (ad5) observed in several types of cancer, the fiber region of ad5, apart from its tail, was replaced by adenovirus serotype 35 (ad35). the chimeric ad5/f35 adenoviral vector did not exhibit any significant enhancement of transduction efficiency. cd46, a receptor for ad35, was expressed in relatively small amounts in most of the cancer cells examined. therefore, we investigated the pivotal factor(s) that render cancer ce ... | 2013 | 23403990 |
| a phase i double blind, placebo-controlled, randomized study of a multigenic hiv-1 adenovirus subtype 35 vector vaccine in healthy uninfected adults. | we conducted a phase i, randomized, double-blind, placebo-controlled trial to assess the safety and immunogenicity of escalating doses of two recombinant replication defective adenovirus serotype 35 (ad35) vectors containing gag, reverse transcriptase, integrase and nef (ad35-grin) and env (ad35-env), both derived from hiv-1 subtype a isolates. the trial enrolled 56 healthy hiv-uninfected adults. | 2012 | 22870265 |
| vaccination with adenovirus serotypes 35, 26, and 48 elicits higher levels of innate cytokine responses than adenovirus serotype 5 in rhesus monkeys. | adenovirus (ad) vaccine vectors have proven highly immunogenic in multiple experimental models, but the innate immune responses induced by these vectors remain poorly characterized. here we report innate cytokine responses to 5 different ad vectors in 26 rhesus monkeys. vaccination with adenovirus serotype 35 (ad35), ad26, and ad48 induced substantially higher levels of antiviral (gamma interferon [ifn-γ], 10-kda gamma interferon-induced protein [ip-10]) and proinflammatory (interleukin 1 recept ... | 2012 | 22787208 |
| type i ifn induced by adenovirus serotypes 28 and 35 has multiple effects on t cell immunogenicity. | recombinant adenovirus (rad) vectors are being investigated as vaccine delivery vehicles in preclinical and clinical studies. rads constructed from different serotypes differ in receptor usage, tropism, and ability to activate cells, aspects of which likely contribute to their different immunogenicity profiles. in this study, we compared the infectivity and cell stimulatory capacity of recombinant adenovirus serotype 5 (rad5), recombinant adenovirus serotype 28 (rad28), and recombinant adenoviru ... | 2012 | 22586038 |
| attenuation of cd4+ t-cell function by human adenovirus type 35 is mediated by the knob protein. | the complement-regulatory protein cd46 is the primary receptor for human adenovirus type 35 (hadv-35) and can regulate human immune-cell activation. cd4(+) t-cells are critical for initiating and maintaining adaptive immunity elicited by infection or vaccination. it was reported previously that hadv-35 can bind these cells and suppress their activation. the data reported here demonstrate that recombinant trimeric hadv-35 knob proteins alone can induce cd46 receptor downregulation and inhibit int ... | 2012 | 22357750 |
| improving gene transfer in human renal carcinoma cells: utilization of adenovirus vectors containing chimeric type 5 and type 35 fiber proteins. | the transduction efficacy of adenovirus serotype 5 (ad5) vector in human renal carcinoma cells is generally low due to the down-regulated expression of coxsackie and adenovirus receptor (car) in target cells. by contrast, the infectivity of adenovirus serotype 35 vectors depends on the binding rate to cd46 receptor, independent of car. in this study, we examined whether an adenovirus vector containing chimeric type 5 and type 35 fiber proteins (ad5/f35) increases transduction efficiency compared ... | 2010 | 22993573 |
| transduction properties of adenovirus serotype 35 vectors after intravenous administration into nonhuman primates. | adenovirus serotype 35 (ad35) vectors have shown promise as effective gene delivery vehicles. however, the transduction profiles of ad35 vectors in conventional mice allow only a limited estimation of transduction properties of these vectors, because the mouse analog of the subgroup b ad receptor, cd46, is restricted to the testis. in order to assess the transduction properties of ad35 vectors more completely, we performed transduction experiments using cynomolgus monkeys, which ubiquitously exp ... | 2008 | 28178464 |
| multiple cases of life-threatening adenovirus pneumonia in a mental health care center. | eighteen cases of pneumonia developed during an outbreak of adenovirus infection in a chronic psychiatric care facility. the six patients most severely affected were admitted to the intensive care unit (icu) at our institution. four of these patients developed septic shock. we report the presentation, disease progression, and response to treatment of these patients. clinical features consisted of high fever, nonproductive cough, and dense lower lobe infiltrates. laboratory abnormalities included ... | 1998 | 9476884 |
| characterization of human adenovirus 35 and derivation of complex vectors. | replication-deficient recombinant adenoviral vectors based on human serotype 35 (ad35) are desirable due to the relatively low prevalence of neutralizing antibodies in the human population. the structure of the viral genome and life cycle of ad35 differs from the better characterized ad5 and these differences require differences in the strategies for the generation of vectors for gene delivery. | 2010 | 20959004 |
| antigen capsid-display on human adenovirus 35 via pix fusion is a potent vaccine platform. | durable protection against complex pathogens is likely to require immunity that comprises both humoral and cellular responses. while heterologous prime-boost regimens based on recombinant, replication-incompetent adenoviral vectors (adv) and adjuvanted protein have been able to induce high levels of concomitant humoral and cellular responses, complex manufacturing and handling in the field may limit their success. to combine the benefits of genetic and protein-based vaccination within one vaccin ... | 2017 | 28362809 |
| oncolytic virotherapy for osteosarcoma using midkine promoter-regulated adenoviruses. | oncolytic virotherapy using adenoviruses has potential therapeutic benefits for a variety of cancers. we recently developed moa5, a tumor-specific midkine promoter-regulated oncolytic vector based on human adenovirus serotype 5 (ad5). we modified the binding tropism of moa5 by replacing the cell-binding domain of the ad5 fiber knob with that from another adenovirus serotype 35 (ad35); the resulting vector was designated moa35. here we evaluated the therapeutic efficacies of moa5 and moa35 for hu ... | 2014 | 24577130 |
| enhanced antitumor immunotherapeutic effect of b-cell-based vaccine transduced with modified adenoviral vector containing type 35 fiber structures. | for successful clinical tumor immunotherapy outcomes, strong immune responses against tumor antigens must be generated. cell-based vaccines compromise one strategy with which to induce appropriate strong immune responses. previously, we established a natural killer t-cell (nkt) ligand-loaded, adenoviral vector-transduced b-cell-based anticancer cellular vaccine. to enhance tumor antigen delivery to b cells, we established a modified adenoviral vector (ad-k35) that encoded a truncated form of the ... | 2014 | 24225639 |
| enhanced antitumor efficacy of fiber-modified, midkine promoter-regulated oncolytic adenovirus in human malignant mesothelioma. | oncolytic virotherapy using adenoviruses has potential for therapeutic benefits in malignant mesothelioma. however, the downregulation of coxsackie virus/adenovirus receptor (car) expression is frequently a critical rate-limiting factor that impedes the effectiveness of adenovirus serotype 5 (ad5)-based vectors in many cancer types. we evaluated car (ad5 receptor) and cd46 (adenovirus serotype 35 [ad35] receptor) expression in six human malignant mesothelioma cell lines. very low car expression ... | 2013 | 23962292 |
| relationship of e1 and e3 regions of human adenovirus 35 to those of human adenovirus subgroups a, c and d. | cloned psti fragments of human adenovirus 35 (av35) genome were compared with the dna of representatives of human adenovirus subgroups a (type 12), b (type 7), c (types 1, and 5), d (type 8), and e (type 4), using blot hybridization techniques. the e1b region of av35 was found to be more distantly related to those of other subgroups than e1a regions sequences and examined by others. dna hybridization was observed only between e1b of av35 and the dna of av4, thus the recombinant constructed might ... | 1989 | 2534900 |
| a peptide-based plasmodium falciparum circumsporozoite assay to test for serum antibody responses to pre-erythrocyte malaria vaccines. | various pre-erythrocyte malaria vaccines are currently in clinical development, and among these is the adenovirus serotype 35-based circumsporozoite (cs) vaccine produced on per.c6 cells. although the immunological correlate of protection against malaria remains to be established, the cs antibody titer is a good marker for evaluation of candidate vaccines. here we describe the validation of an anti-plasmodium falciparum circumsporozoite antibody enzyme-linked immunosorbent assay (elisa) based on ... | 2011 | 21411600 |
| identification of cd46 binding sites within the adenovirus serotype 35 fiber knob. | species b human adenoviruses (ads) are often associated with fatal illnesses in immunocompromised individuals. recently, species b ads, most of which use the ubiquitously expressed complement regulatory protein cd46 as a primary attachment receptor, have gained interest for use as gene therapy vectors. in this study, we focused on species b ad serotype 35 (ad35), whose trimeric fiber knob domain binds to three cd46 molecules with a kd (equilibrium dissociation constant) of 15.5 nm. to study the ... | 2007 | 17898059 |
| assessment of the safety and immunogenicity of 2 novel vaccine platforms for hiv-1 prevention: a randomized trial. | a prophylactic hiv-1 vaccine is a global health priority. | 2016 | 26833336 |
| recombinant ad35 adenoviral proteins as potent modulators of human t cell activation. | the protein cd46 protects cells from complement attack by regulating cleavage of c3b and c3d. cd46 also regulates the adaptive immune response by controlling t cell activation and differentiation. co-engagement of the t cell receptor and cd46 notably drives t cell differentiation by switching production of ifnγ to secretion of anti-inflammatory il-10. this regulatory pathway is altered in several chronic inflammatory diseases highlighting its key role for immune homeostasis. the manipulation of ... | 2015 | 25251258 |
| generation of a replication-deficient recombinant human adenovirus type 35 vector using bacteria-mediated homologous recombination. | the use of adenovirus type 35 (ad35) as a vector in vaccine and gene therapy studies is promising due to its broad cell tropism and low seroprevalence in humans. however, to date, a simple and effective system for producing recombinant ad35 (rad35) has not been well developed. this report describes a two-plasmid ad35-easy system to facilitate the production of recombinant ad35 (rad35). the system employed the pad35-shuttle vector for foreign gene transfer and the pad35-backbone vector to provide ... | 2011 | 21763350 |