The Experts below are selected from a list of 14934 Experts worldwide ranked by ideXlab platform
Hiroshi Kiyono - One of the best experts on this subject based on the ideXlab platform.
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The development of Mucosal Vaccine using bacterial function for targeting Mucosal tissues
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, 2014Co-Authors: Hidehiko Suzuki, Masuo Kondoh, Kiyohito Yagi, Hiroshi Kiyono, Jun KunisawaAbstract:Most pathogens invade body through the Mucosal epithelium, which is a primary target to prevent the infectious diseases. Mucosal Vaccine has been considered to be an effective strategy to establish immunosurveillance against pathogens by the induction of antigen-specific immune responses at both Mucosal and systemic immune compartments. The development of antigen delivery system and Mucosal adjuvants are required for the sufficient induction of protective immunity in the development of Mucosal Vaccine. In this review, we shed light on the recent advances in the development of antigen delivery system using microbial functions for Mucosal Vaccines.
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m cells expressing the complement c5a receptor are efficient targets for Mucosal Vaccine delivery
European Journal of Immunology, 2011Co-Authors: Daeim Jung, Inyoung Yang, Tomonori Nochi, Hiroshi Kiyono, Yongsuk JangAbstract:In the Mucosal immune system, M cells are known as specialized epithelial cells that take up luminal antigens, although the receptors on M cells and the mechanism of antigen uptake into M cells are not well-understood. Here, we report the expression of the complement C5a receptor (C5aR) on the apical surface of M cells. C5ar mRNA expression in co-cultured Caco-2 human M-like cells was six-fold higher than in mono-cultured cells. C5aR expression was detected together with glycoprotein 2, an M-cell-specific protein, on the apical surface of M-like cells and mouse Peyer's patch M cells. Interestingly, after oral administration of Yersinia enterocolitica which expresses outer membrane protein H (OmpH) that is homologous to the Skp α1 domain of Escherichia coli, a ligand of C5aR, dense clustering and phosphorylation of C5aR were detected in M cells. Finally, targeted antigen delivery to M cells using C5aR as a receptor was achieved using the OmpH α1 of Y. enterocolitica such that the induction of ligand-conjugated antigen-specific immune responses was confirmed in mice after oral immunization of the OmpH β1α1-conjugated antigen. Collectively, we identified C5aR expression on M cells and suggest that C5aR could be used as a target receptor for Mucosal antigen delivery.
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craniofacial Mucosal immune system importance of its unique organogenesis and function in the development of a Mucosal Vaccine
Advances in oto-rhino-laryngology, 2011Co-Authors: Kazunari Okada, Tatsuya Yamasoba, Hiroshi KiyonoAbstract:Mucosa-associated lymphoid tissues (MALT) play a critical role as inductive sites for the initiation of antigen-specific protective immunity against pathogens penetrating the mucus membranes. Nasopharynx-associated lymphoid tissue (NALT), situated at the bottom of the rodent nasal cavity, is thought to be an important site for the induction of antigen-specific immune response to inhaled antigens. In addition, we have recently shown that tear duct-associated lymphoid tissue (TALT), present in the murine tear duct bridging the ocular and nasal cavities, is involved in the induction and regulation of both nasal and ocular immunity. Interestingly, cellular requirements for the organogenesis of NALT and TALT are quite different from those of other MALT (e.g. Peyer’s patches; PPs) and peripheral lymphoid tissues. Moreover, Mucosal imprinting molecules of NALT and TALT inducer cells are totally independent of currently known chemokines and adhesion molecules in PPs and lymph nodes, such as the CXCR5-CXCL13, α4β1 integrin-vascular cell adhesion molecule-1 (VCAM1), and CCR9-CCL25 axes. NALT and TALT lymphocytes are also independent of these tissue-specific migration molecules. Together with already-characterized conjunctiva-associated lymphoid tissue (CALT ), which has been demonstrated to play a critical role in ocular defense, the MALT associated with the head region seems to be coordinately organizing the unique craniofacial Mucosal immune system of the ocular, nasal, oral-pharynx mucus membranes. Clarification of the immunological network of this unique craniofacial immune system will facilitate the development of a safe and effective Mucosal Vaccine against respiratory and ocular infections.
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Current progress in the development of Mucosal Vaccines
Nihon rinsho. Japanese journal of clinical medicine, 2011Co-Authors: Natsumi Takeyama, Yoshikazu Yuki, Hiroshi KiyonoAbstract:Abstract Mucosal vaccination has several advantages compared with that of injection-type vaccination. Secretory IgA(SIgA) produced at Mucosal surface plays a key role for inactivation of toxins and inhibition of pathogen invasion. Although oral or nasal vaccination with attenuated live microorganisms have been shown to be effective in the induction of protective immunity, these types of Vaccine have the ability to infect transiently to the host. For the development of safe and effective Mucosal Vaccine, an obvious strategy is the preparation of inactivated subunit-type Mucosal Vaccine. Here we introduce our frontier technology for the development of rice-based oral Vaccines, as a new generation of Mucosal Vaccine. Further, we also discuss recent progress in the development of other types of Mucosal Vaccine and adjuvant.
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Transgenic Rice for Mucosal Vaccine and Immunotherapy
Allergy Frontiers: Future Perspectives, 2010Co-Authors: Yoshikazu Yuki, Fumio Takaiwa, Hiroshi KiyonoAbstract:The use of recombinant allergen–based immunotherapy has improved current practical approaches to allergy treatment and has revealed potential new clinical strategies for the control of allergic diseases. Oral immunotherapy using a rice-based oral Vaccine is one attractive strategy that was shown to be effective for the control of pollen allergies. When the peptides for a T cell specific to Japanese cedar (Cryptomeria japonica) pollen are expressed by transgenic rice seeds and orally administered to naive mice, it induced oral tolerance responsible for the inhibition of the IgE-mediated allergic response, suppression of histamine production, and reduction of clinical symptoms (e.g., sneezing), thereby preventing the development of this pollen-induced allergy. The results may have important implications for the development of peptide-based Mucosal Vaccines and for immunotherapy to control allergic diseases. The potential of transgenic rice as a new Mucosal Vaccine-delivery vehicle for the control of allergies is reviewed from the perspective of future directions for the development of clinically effective allergy Vaccines.
Mingtao Zeng - One of the best experts on this subject based on the ideXlab platform.
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An adenoviral vector-based Mucosal Vaccine is effective in protection against botulism.
Gene therapy, 2009Co-Authors: Michael E. Pichichero, Lance L. Simpson, Elias, Leonard A. Smith, Mingtao ZengAbstract:A replication-incompetent adenoviral vector encoding the heavy chain C-fragment (HC50) of botulinum neurotoxin type C (BoNT/C) was evaluated as a Mucosal Vaccine against botulism in a mouse model. Single intranasal inoculation of the adenoviral vector elicited a high level of HC50-specific IgG, IgG1 and IgG2a in sera and IgA in Mucosal secretions as early as 2 weeks after vaccination. The antigen-specific serum antibodies were maintained at a high level at least until the 27th week. Immune sera showed high potency in neutralizing BoNT/C as indicated by in vitro toxin neutralization assay. The mice receiving single dose of 2 × 107 p.f.u. (plaque-forming unit) of adenoviral vector were completely protected against challenge with up to 104 × MLD50 of BoNT/C. The protective immunity showed Vaccine dose dependence from 105 to 2 × 107 p.f.u. of adenoviral vector. In addition, animals receiving single intranasal dose of 2 × 107 p.f.u. adenoviral vector could be protected against 100 × MLD50 27 weeks after vaccination. Animals with preexisting immunity to adenovirus could also be vaccinated intranasally and protected against lethal challenge with BoNT/C. These results suggest that the adenoviral vector is a highly effective gene-based Mucosal Vaccine against botulism.
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detoxified lethal toxin as a potential Mucosal Vaccine against anthrax
Clinical and Vaccine Immunology, 2008Co-Authors: Qingfu Xu, Mingtao ZengAbstract:The nontoxic mutant lethal factor (mLF; which has the E687C substitution) and functional protective antigen (PA63) of Bacillus anthracis were evaluated for their use as Mucosal Vaccines against anthrax in A/J mice. Intranasal vaccination of three doses of 30 μg of mLF or 60 μg of PA63 elicited significant serum and Mucosal antibody responses, with anthrax lethal toxin-neutralizing titers of 40 and 60 in immune sera, respectively. However, only 30% and 60% of the vaccinated animals in the two groups could survive a challenge with 100 times the 50% lethal dose of B. anthracis Sterne spores, respectively. In contrast, vaccination with three doses of the combination of 30 μg of mLF and 60 μg of PA63, the detoxified lethal toxin, elicited antibody responses against LF and PA significantly higher than those elicited after vaccination with mLF or PA63 individually by use of the same dose and schedule. Vaccination with the detoxified lethal toxin resulted in significantly higher lethal toxin-neutralizing antibody titers in sera (titer, 90). Animals vaccinated with three doses of the detoxified lethal toxin were completely protected against the spore challenge. The data suggest that mLF and PA63 have a mutual enhancement effect for evoking systemic and Mucosal immune responses and that the detoxified lethal toxin can be used as an efficient Mucosal Vaccine against anthrax.
Hiroyuki Kayamuro - One of the best experts on this subject based on the ideXlab platform.
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Identification of New Candidates as Mucosal Vaccine Adjuvant in TNF Family Cytokines
Advances in experimental medicine and biology, 2010Co-Authors: Hiroyuki Kayamuro, Yasuo Yoshioka, Yasuhiro Abe, Kazufumi Katayama, Tomoaki Yoshikawa, Norio Itoh, Shuhei Arita, Tetsuya Nomura, Haruhiko Kamada, Shinichi TsunodaAbstract:Preventing infection at the pathogen portal of entry through induction of Mucosal immunity is an exciting prospect. Mucosal Vaccines administered either orally or nasally are effective in inducing antigen-specific immune responses in both the systemic and the Mucosal compartment. However, the Mucosal antigen-specific immune response is weak, because most protein antigens applied Mucosally can evoke only a weak immune response. One strategy to overcome the weakness of the immune response is the co-administration of Mucosal adjuvant with the Vaccine antigen. Unfortunately, the development of a safe and effective Mucosal adjuvant has proved challenging. Cytokines are promising adjuvants because they are safe, human-derived materials and display potent immune-modulating functions. Members of the tumor necrosis factor (TNF)/TNF receptor (TNFR) superfamily are critically involved in maintaining homeostasis of the immune system. We determined the potential of TNF superfamily cytokines as Mucosal adjuvants for induction of Mucosal immune responses.
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Interleukin-1 Family Cytokines as Mucosal Vaccine Adjuvants for Induction of Protective Immunity against Influenza Virus
Journal of virology, 2010Co-Authors: Hiroyuki Kayamuro, Yasuo Yoshioka, Yasuhiro Abe, Kazufumi Katayama, Tomoaki Yoshikawa, Shuhei Arita, Tetsuya Nomura, Ritsuko Kubota-koketsu, Kazuyoshi Ikuta, Shigefumi OkamotoAbstract:A safe and potent adjuvant is needed for development of Mucosal Vaccines against etiological agents, such as influenza virus, that enter the host at Mucosal surfaces. Cytokines are potential adjuvants for Mucosal Vaccines because they can enhance primary and memory immune responses enough to protect against some infectious agents. For this study, we tested 26 interleukin (IL) cytokines as Mucosal Vaccine adjuvants and compared their abilities to induce antigen (Ag)-specific immune responses against influenza virus. In mice intranasally immunized with recombinant influenza virus hemagglutinin (rHA) plus one of the IL cytokines, IL-1 family cytokines (i.e., IL-1α, IL-1β, IL-18, and IL-33) were found to increase Ag-specific immunoglobulin G (IgG) in plasma and IgA in Mucosal secretions compared to those after immunization with rHA alone. In addition, high levels of both Th1- and Th2-type cytokines were observed in mice immunized with rHA plus an IL-1 family cytokine. Furthermore, mice intranasally immunized with rHA plus an IL-1 family cytokine had significant protection against a lethal influenza virus infection. Interestingly, the adjuvant effects of IL-18 and IL-33 were significantly decreased in mast cell-deficient W/W(v) mice, indicating that mast cells have an important role in induction of Ag-specific Mucosal immune responses induced by IL-1 family cytokines. In summary, our results demonstrate that IL-1 family cytokines are potential Mucosal Vaccine adjuvants and can induce Ag-specific immune responses for protection against pathogens like influenza virus.
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Mutant TNF-alpha, mTNF-K90R, is a novel candidate adjuvant for a Mucosal Vaccine against HIV.
Die Pharmazie, 2010Co-Authors: Hiroyuki Kayamuro, Yasuhiro Abe, Kazufumi Katayama, Tokuyuki Yoshida, Kohei Yamashita, Tomoaki Yoshikawa, Yuichi Kawai, Y Yoshioka, Tadanori Mayumi, Takachika HiroiAbstract:The development of a safe and effective Mucosal Vaccine adjuvant is a crucial step for the development of Vaccines against human immunodeficiency virus type-1 (HIV). We have previously reported that a mutant tumor necrosis factor-alpha (TNF-alpha), mTNF-K90R, possessed strong Mucosal Vaccine adjuvant activities in mice. Here, we evaluated the potential of mTNF-K90R as a Mucosal Vaccine adjuvant for the induction of systemic and Mucosal immune responses against HIV. Nasal immunization of BALB/c mice with 5 microg of an HIV gp120 env protein immunogen together with mTNF-K90R induced higher serum anti-HIV gp120 protein immunoglobulin G (IgG) responses than gp120 alone. Furthermore, mTNF-K90R induced anti-gp120 IgA responses in nasal as well as vaginal washes from immunized mice, although these were not administration sites. Again, responses with mTNF-K90R were higher than with gp120 alone. These results indicate that mTNF-K90R may be applicable as aMucosal adjuvant for HIV vaccination to induce both systemic and Mucosal immune responses.
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application of bioactive mutant tnf alpha to a Mucosal Vaccine adjuvant
Yakugaku Zasshi-journal of The Pharmaceutical Society of Japan, 2010Co-Authors: Hiroyuki Kayamuro, Yasuo Yoshioka, Yasuhiro Abe, Haruhiko Kamada, Shinichi Tsunoda, Yasuo TsutsumiAbstract:A large number of emerging pathogens, such as severe acute respiratory syndrome (SARS), human immunodeficiency virus (HIV), and influenza virus are Mucosally transmitted and must cross Mucosal barriers to infect the host. Thus, to induce a maximal protective effect, it is desirable to apply Vaccines by the Mucosal route where virus infections start. Mucosal Vaccines administered either orally or nasally have been shown to be effective in inducing antigen-specific immune responses at both systemic and Mucosal compartments. However the Mucosal antigen-specific immune response is weak because most protein antigens can evoke only a weak immune response when they are applied Mucosally. Therefore, one strategy to overcome the weakness of the immune response is a co-administration of Mucosal adjuvant with the Vaccine antigen. Unfortunately, the development of safe and effective Mucosal adjuvant has proved to be challenging. Cytokines are promising adjuvants because they are human-derived safe material and display potent immune-modulating functions. In this regards, we have created a mutant tumor necrosis factor-alpha (TNF-alpha), mTNF-K90R, that exhibits high bioactivity and resistance to proteases. In this report, we examined the potential of mTNF-K90R as a Mucosal adjuvant and evaluated its effectiveness and safety.
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TNF superfamily member, TL1A, is a potential Mucosal Vaccine adjuvant.
Biochemical and biophysical research communications, 2009Co-Authors: Hiroyuki Kayamuro, Yasuo Yoshioka, Yasuhiro Abe, Kazufumi Katayama, Tokuyuki Yoshida, Kohei Yamashita, Tomoaki Yoshikawa, Takachika Hiroi, Norio Itoh, Yuichi KawaiAbstract:The identification of cytokine adjuvants capable of inducing an efficient Mucosal immune response against viral pathogens has been long anticipated. Here, we attempted to identify the potential of tumor necrosis factor superfamily (TNFS) cytokines to function as Mucosal Vaccine adjuvants. Sixteen different TNFS cytokines were used to screen Mucosal Vaccine adjuvants, after which their immune responses were compared. Among the TNFS cytokines, intranasal immunization with OVA plus APRIL, TL1A, and TNF-alpha exhibited stronger immune response than those immunized with OVA alone. TL1A induced the strongest immune response and augmented OVA-specific IgG and IgA responses in serum and Mucosal compartments, respectively. The OVA-specific immune response of TL1A was characterized by high levels of serum IgG1 and increased production of IL-4 and IL-5 from splenocytes of immunized mice, suggesting that TL1A might induce Th2-type responses. These findings indicate that TL1A has the most potential as a Mucosal adjuvant among the TNFS cytokines.
Herman F. Staats - One of the best experts on this subject based on the ideXlab platform.
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Mucosal Vaccine development for botulinum intoxication.
Expert review of vaccines, 2007Co-Authors: Kohtaro Fujihashi, Herman F. Staats, Shunji Kozaki, David W. PascualAbstract:Botulism has classically been considered to be a food- and water-borne disease. However, it was recently classified by the US National Institute of Allergy and Infectious Diseases (National Institute of Health) and the US Centers for Disease Control and Prevention as a Category A agent. Thus, the botulinum exotoxin, a neurotoxin, could be easily disseminated by bioterrorists through the air-borne route with a high morbidity and mortality rate. In this regard, a high priority should be given to the development of a safe and effective Mucosal Vaccine to protect against botulinum neurotoxins (BoNTs) since it is well known that the Mucosal immune system is the first line of defense against major pathogens. Further, Mucosal immunization has been shown to induce both Mucosal and systemic immunity to pathogens. By contrast, the current injection-type Vaccine only provides protective immunity in the systemic compartment. Clearly, the development of a safe and effective Mucosal Vaccine against this toxin should be...
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Mucosal immunity to infection with implications for Vaccine development
Current Opinion in Immunology, 1994Co-Authors: Herman F. Staats, Raymond J Jackson, Mariarosaria Marinaro, Ichiro TakahashiAbstract:The induction of effective Mucosal immunity that also provides systemic immunity is a considerable challenge. Over the past two years, efforts to develop novel Mucosal Vaccine delivery systems to induce Mucosal immunity against bacterial and viral diseases, including HIV, have dramatically increased. Here we cite novel Vaccines and delivery systems being used to establish effective Mucosal immunity.
Magdalena M Gherardi - One of the best experts on this subject based on the ideXlab platform.
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recombinant poxviruses as Mucosal Vaccine vectors
Journal of General Virology, 2005Co-Authors: Magdalena M Gherardi, Mariano EstebanAbstract:The majority of infections initiate their departure from a Mucosal surface, such as Human immunodeficiency virus (HIV), a sexually transmitted virus. Therefore, the induction of Mucosal immunity is a high priority in the development of Vaccines against Mucosal pathogens. The selection of an appropriate antigen delivery system is necessary to induce an efficient Mucosal immune response. Poxvirus vectors have been the most intensively studied live recombinant vector, and numerous studies have demonstrated their ability to induce Mucosal immune responses against foreign expressed antigens. Previous studies have demonstrated that recombinants based on the attenuated modified vaccinia virus Ankara (MVA) vector were effective in inducing protective responses against different respiratory viruses, such as influenza and respiratory syncytial virus, following immunization via Mucosal routes. Recent studies performed in the murine and macaque models have shown that recombinant MVA (rMVA) does not only stimulate HIV-specific immunity in the genital and rectal tracts following Mucosal delivery, but can also control simian/human immunodeficiency viraemia and disease progression. In addition, a prime-boost vaccination approach against tuberculosis emphasized the importance of the intranasal rMVA antigen delivery to induce protective immunity against Mycobacterium tuberculosis. The aim of this review is to summarize the studies employing recombinant poxviruses, specifically rMVA as a Mucosal delivery vector. The results demonstrate that rMVAs can activate specific immune responses at Mucosal surfaces, and encourage further studies to characterize and improve the MVA Mucosal immunogenicity of poxvirus vectors.