The Experts below are selected from a list of 37668 Experts worldwide ranked by ideXlab platform

Curtis Cooper - One of the best experts on this subject based on the ideXlab platform.

Ken J Ishii - One of the best experts on this subject based on the ideXlab platform.

  • novel strategies to improve dna Vaccine Immunogenicity
    Current Gene Therapy, 2011
    Co-Authors: Cevayir Coban, Taiki Aoshi, Toshihiro Horii, Shizuo Akira, Kouji Kobiyama, Fumihiko Takeshita, Ken J Ishii
    Abstract:

    DNA Vaccines can induce both humoral and cellular immune responses in animals. Some DNA Vaccines are already licensed for infectious diseases such as West Nile virus encephalitis in horses. When used in humans, however, DNA Vaccines suffer from lower Immunogenicity profiles. Although the reasons for this are poorly understood, various hypotheses have been proposed. This review aims to provide better understanding of the molecular and immunological mechanisms by which DNA Vaccines work and how such knowledge can be used to bring about improvements in their efficacy. Recent studies have provided evidence that the ‘adjuvant effect’ of plasmid DNA is mediated by its doublestranded structure. This structure activates stimulator of interferon genes/TANK-binding kinase 1 (STING/TBK1)- dependent innate immune signaling pathways in the absence of Toll-like receptors. Indeed, type-I interferons (IFNs), induced in vivo via the STING/TBK1 pathway, were found to be crucial for both direct- and indirect-antigen presentation via distinct cell types (i.e. dendritic cells (DC) and muscle cells, respectively). Importantly, incorporation of TBK1 into a DNA Vaccine was found to enhance the antigen-specific humoral immune responses targeting the Plasmodium falciparum serine repeat antigen (SERA), a candidate Vaccine antigen expressed in the blood-stages of human malaria parasites. Thus, the results of these studies may offer new ways to develop DNA Vaccines, as well as delivering novel Vaccine adjuvants against infectious diseases.

  • Innate immune control of nucleic acid-based Vaccine Immunogenicity.
    Expert review of vaccines, 2009
    Co-Authors: Shohei Koyama, Cevayir Coban, Taiki Aoshi, Toshihiro Horii, Shizuo Akira, Ken J Ishii
    Abstract:

    Optimal Vaccine efficacy requires not only a protective antigen, but also a strong immune activator as an adjuvant. Most viral Vaccines, such as influenza Vaccines and nonviral genetic Vaccines (e.g., DNA Vaccines), contain nucleic acids, which appear to act as essential ‘built-in’ adjuvants. Specific receptors, including Toll-like receptors, retinoic acid-inducible protein-I-like receptors, and nucleotide-binding oligomerization domain-like receptors can detect specific nucleic acid patterns, depending on the immunized tissue, cell type and intracellular localization. The resulting immune activation is uniquely regulated by intra- and intercellular signaling pathways, which are indispensable for the ensuing Vaccine Immunogenicity, such as antigen-specific T- and B-cell responses. Thus, elucidation and manipulation of immune signaling and interactions by nucleic acid adjuvants are essential for maximizing the Immunogenicity and safety of viral and DNA Vaccines.

  • Toll or Toll-Free Adjuvant Path Toward the Optimal Vaccine Development
    Journal of Clinical Immunology, 2007
    Co-Authors: Ken J Ishii
    Abstract:

    Successful Vaccines contain an adjuvant component that activates the innate immune system, thereby eliciting antigen-specific immune responses. Many adjuvants appear to be ligands for toll-like receptors (TLR), which are thus promising targets for the development of novel adjuvants to elicit Vaccine Immunogenicity. However, recent evidence suggests that some adjuvants activate the innate immune system in a TLR-independent manner possibly through other pattern recognition receptors and signaling machinery. In particular, newly identified intracellular retinoic-acid-inducible gene (RIG)-like receptors, NOD-like receptors, or even as yet unknown recognition machinery for the adjuvant may regulate TLR-independent Vaccine Immunogenicity. To develop optimal Vaccines, it will be critical to understand how TLR-dependent and TLR-independent innate immune activation, by various adjuvants, control the consequent adaptive immune responses to Vaccine.

Nikolai Petrovsky - One of the best experts on this subject based on the ideXlab platform.

  • Molecular mechanisms for enhanced DNA Vaccine Immunogenicity
    Expert Review of Vaccines, 2015
    Co-Authors: Nikolai Petrovsky
    Abstract:

    In the two decades since their initial discovery, DNA Vaccines technologies have come a long way. Unfortunately, when applied to human subjects inadequate Immunogenicity is still the biggest challenge for practical DNA Vaccine use. Many different strategies have been tested in preclinical models to address this problem, including novel plasmid vectors and codon optimization to enhance antigen expression, new gene transfection systems or electroporation to increase delivery efficiency, protein or live virus vector boosting regimens to maximise immune stimulation, and formulation of DNA Vaccines with traditional or molecular adjuvants. Better understanding of the mechanisms of action of DNA Vaccines has also enabled better use of the intrinsic host response to DNA to improve Vaccine Immunogenicity. This review summarizes recent advances in DNA Vaccine technologies and related intracellular events and how these might impact on future directions of DNA Vaccine development.

  • Comparative Safety of Vaccine Adjuvants: A Summary of Current Evidence and Future Needs
    Drug Safety, 2015
    Co-Authors: Nikolai Petrovsky
    Abstract:

    Use of highly pure antigens to improve Vaccine safety has led to reduced Vaccine Immunogenicity and efficacy. This has led to the need to use adjuvants to improve Vaccine Immunogenicity. The ideal adjuvant should maximize Vaccine Immunogenicity without compromising tolerability or safety. Unfortunately, adjuvant research has lagged behind other Vaccine areas such as antigen discovery, with the consequence that only a very limited number of adjuvants based on aluminium salts, monophosphoryl lipid A and oil emulsions are currently approved for human use. Recent strategic initiatives to support adjuvant development by the National Institutes of Health should translate into greater adjuvant choices in the future. Mechanistic studies have been valuable for better understanding of adjuvant action, but mechanisms of adjuvant toxicity are less well understood. The inflammatory or danger-signal model of adjuvant action implies that increased Vaccine reactogenicity is the inevitable price for improved Immunogenicity. Hence, adjuvant reactogenicity may be avoidable only if it is possible to separate inflammation from adjuvant action. The biggest remaining challenge in the adjuvant field is to decipher the potential relationship between adjuvants and rare Vaccine adverse reactions, such as narcolepsy, macrophagic myofasciitis or Alzheimer’s disease. While existing adjuvants based on aluminium salts have a strong safety record, there are ongoing needs for new adjuvants and more intensive research into adjuvants and their effects.

  • an inactivated vero cell grown japanese encephalitis Vaccine formulated with advax a novel inulin based adjuvant induces protective neutralizing antibody against homologous and heterologous flaviviruses
    Journal of General Virology, 2010
    Co-Authors: Mario Lobigs, Hiroko Toriniwa, Tomoyoshi Komiya, Paivi Lobigs, Peter D Cooper, Roy A. Hall, Megan Pavy, Nikolai Petrovsky
    Abstract:

    Advax is a polysaccharide-based adjuvant that potently stimulates Vaccine Immunogenicity without the increased reactogenicity seen with other adjuvants. This study investigated the Immunogenicity of a novel Advax-adjuvanted Vero cell culture candidate Vaccine against Japanese encephalitis virus (JEV) in mice and horses. The results showed that, in mice, a two-immunization, low-dose (50 ng JEV antigen) regimen with adjuvanted Vaccine produced solid neutralizing immunity comparable to that elicited with live ChimeriVax-JE immunization and superior to that elicited with tenfold higher doses of a traditional non-adjuvanted JEV Vaccine (JE-VAX; Biken Institute) or a newly approved alum-adjuvanted Vaccine (Jespect; Novartis). Mice vaccinated with the Advax-adjuvanted, but not the unadjuvanted Vaccine, were protected against live JEV challenge. Equine immunizations against JEV with Advax-formulated Vaccine similarly showed enhanced Vaccine Immunogenicity, confirming that the adjuvant effects of Advax are not restricted to rodent models. Advax-adjuvanted JEV Vaccine elicited a balanced T-helper 1 (Th1)/Th2 immune response against JEV with protective levels of cross-neutralizing antibody against other viruses belonging to the JEV serocomplex, including Murray Valley encephalitis virus (MVEV). The adjuvanted JEV Vaccine was well tolerated with minimal reactogenicity and no systemic toxicity in immunized animals. The cessation of manufacture of traditional mouse brain-derived unadjuvanted JEV Vaccine in Japan has resulted in a JEV Vaccine shortage internationally. There is also an ongoing lack of human Vaccines against other JEV serocomplex flaviviruses, such as MVEV, making this adjuvanted, cell culture-grown JEV Vaccine a promising candidate to address both needs with one Vaccine.

Kevin L. Winthrop - One of the best experts on this subject based on the ideXlab platform.

  • Vaccinations for rheumatoid arthritis.
    Current opinion in rheumatology, 2016
    Co-Authors: Marcia A. Friedman, Kevin L. Winthrop
    Abstract:

    Purpose of reviewRheumatoid arthritis (RA) patients experience increased infectious disease-related morbidity and mortality, and vaccinations represent an important element in their care. However, Vaccine Immunogenicity can be affected by disease-modifying antirheumatic drug (DMARD) therapy, such th

Shaun H Pennington - One of the best experts on this subject based on the ideXlab platform.

  • oral typhoid vaccination with live attenuated salmonella typhi strain ty21a generates ty21a responsive and heterologous influenza virus responsive cd4 and cd8 t cells at the human intestinal mucosa
    The Journal of Infectious Diseases, 2016
    Co-Authors: Ameeka Thompson, Angela D Wright, Adam K A Wright, Kondwani C Jambo, Brian Faragher, Shaun H Pennington, Daniela M. Ferreira, Jill Gilmour
    Abstract:

    Salmonella enterica serovar Typhi is a human-host-restricted intracellular pathogen and the causative agent of typhoid fever. Following ingestion, the bacteria cause systemic illness following invasion via the mucosal surface of the small intestine [1]. In the 1970s, through chemical mutagenesis of pathogenic S. Typhi strain Ty2, a live-attenuated oral typhoid Vaccine, Ty21a, was developed [2]. Vaccination with 3 doses of Ty21a is moderately protective, and although estimates of efficacy vary [3–5], a recently published review calculated a cumulative efficacy of 48% 3 years following vaccination [6]. Ty21a is able to induce humoral and cellular immune responses, both of which have been implicated in protection against disease. While opsonophagocytic antibody function [7], cellular cytotoxicity, proliferation, and cytokine production functionality have been assessed in peripheral blood following vaccination with Ty21a [8–13], cellular immunity at the human intestinal mucosa has never been directly assessed. Numerous studies have demonstrated that cellular immune responses generated through vaccination with Ty21a are primed for mucosal homing [13–15], highlighting the importance of mucosal immunity in defense against disease. Furthermore, it has been demonstrated that the assessment of Vaccine Immunogenicity by peripheral sampling alone provides an incomplete reflection of Vaccine Immunogenicity [16]. It has previously been observed in murine models that previously primed T cells of heterologous specificities are recruited to the lung during influenza virus infection [17]. Although this phenomenon has not been observed in humans, we hypothesized that vaccination with Ty21a could enhance T-cell responses to heterologous antigens at the mucosal surface by a similar mechanism. Through the direct assessment of immunity at the intestinal mucosa, it may be possible to identify mechanisms involved in the induction of protective immunity, which may be manipulated to improve oral Vaccine Immunogenicity. Here, we have assessed cellular immunity in vaccinated volunteers and controls at the duodenal and colonic mucosa and in peripheral blood after 18 days. We have compared and correlated peripheral and mucosal cellular responses with accepted peripheral humoral measures of Vaccine efficacy, providing a unique insight into the relationship between human mucosal and peripheral immune defense.