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News Article | December 6, 2016
Site: phys.org

The river blindness vaccine is being developed using the patented adjuvant technology Advax by biotechnology company Vaxine Pty Ltd in South Australia. The vaccine, which uses a unique sugar-based adjuvant, is set for cattle trials before the end of the year. According to the World Health Organisation, river blindness, also known as onchocerciasis, affects about 17 million people globally. It is spread by blackflies that breed in rivers, infecting humans and cattle with a parasitic worm known as Onchocerca volvulus. The parasites can cause eye inflammation, bleeding, and other complications that ultimately lead to blindness. Advax makes the pathogen in the vaccine more easily recognised by the body's immune system so it can develop appropriate antibodies. The vaccine is being primed for a cattle trial in the United States after successful testing in mice. Vaxine Scientific Director Nikolai Petrovsky said the company planned a two-pronged approach to effectively preventing the disease. "First we're looking to vaccinate the cattle, which are a breeding ground for the parasite," he said. "Then the other side of this is to immunise the children so if they come in contact with the parasite it blocks the infection. "Our technology is a bit like melding a turbocharger to the engine and in this case makes the vaccine dramatically more powerful." Blackflies bite the host, passing on the parasite in the process. The parasitic worms then produce microfilariae that migrate to the skin, eyes and other organs. Onchocerciasis is a major cause of blindness in African, particularly in the western and central parts of the continent. It is also prevalent in many South American countries. River blindness is partly responsible for the reduction of economic productivity in many of those areas, causing vast tracts of arable land to be abandoned. Potential solutions to the problem, such as ivermectin, have been developed but have often led to a resistance to the drugs. Professor Petrovski said one of the main problems was that other methods used aluminium-based adjuvants, which were not always effective. "We offer a new alternative that is not only potentially safer because it is a sugar instead of a metal/salt with high toxicity," he said "Our adjuvant also works for a lot of vaccines that wouldn't work with aluminium. The ones that tried to create an onchocerciasis vaccine didn't take but ours actually works." Vaxine is funded by the US National Institutes of Health to develop polysaccharide adjuvants that have played a vital role in the development of a range of vaccines for infectious diseases, allergies, and cancers. It is internationally renowned for developing the world's first swine flu vaccine during the 2009 pandemic and is active on other fronts including Ebola and Zika virus research. The river blindness vaccine was developed in association with Thomas Jefferson University and the New York Blood Centre in the United States. The group has received a grant from the US Government for the cattle trial and plans to begin tests in the coming weeks. The results of the vaccine's mice trials were published in PLOS Neglected Tropical Diseases. Explore further: Scientists sequence, explore the genome of the river blindness parasite


Feinen B.,Center for Biologics Evaluation and Research | Petrovsky N.,Vaxine Pty. Ltd. | Verma A.,Center for Biologics Evaluation and Research | Merkel T.J.,Center for Biologics Evaluation and Research
Clinical and Vaccine Immunology | Year: 2014

Subunit vaccines against anthrax based on recombinant protective antigen (PA) potentially offer more consistent and less reactogenic anthrax vaccines but require adjuvants to achieve optimal immunogenicity. This study sought to determine in a murine model of pulmonary anthrax infection whether the polysaccharide adjuvant Advax or the innate immune adjuvant murabutide alone or together could enhance PA immunogenicity by comparison to an alum adjuvant. A single immunization with PA plus Advax adjuvant afforded significantly greater protection against aerosolized Bacillus anthracis Sterne strain 7702 than three immunizations with PA alone. Murabutide had a weaker adjuvant effect than Advax when used alone, but when murabutide was formulated together with Advax, an additive effect on immunogenicity and protection was observed, with complete protection after just two doses. The combined adjuvant formulation stimulated a robust, long-lasting B-cell memory response that protected mice against an aerosol challenge 18 months postimmunization with acceleration of the kinetics of the anamnestic IgG response to B. anthracis as reflected by ∼4-fold-higher anti-PA IgG titers by day 2 postchallenge versus mice that received PA with Alhydrogel. In addition, the combination of Advax plus murabutide induced approximately 3-fold-less inflammation than Alhydrogel as measured by in vivo imaging of cathepsin cleavage resulting from injection of ProSense 750. Thus, the combination of Advax and murabutide provided enhanced protection against inhalational anthrax with reduced localized inflammation, making this a promising next-generation anthrax vaccine adjuvanting strategy. Copyright © 2014, American Society for Microbiology. All Rights Reserved.


Patent
University of Strasbourg, French Institute of Health, Medical Research and Vaxine Pty Ltd | Date: 2015-01-29

The present invention relates to the identification of ALMS1 as the missing player involved in the regulation of the insulin-mediated glucose uptake through GLUT4 sorting vesicles, and to the down-regulation of ALMS1 by PKC. Accordingly, the present invention relates to a molecule capable of preventing the binding of PKC on ALMS1 for use for treating or preventing diabetes, in particular type 2 diabetes. In addition, the present invention relates to a method for identifying molecule capable of preventing the binding of PKC on ALMS1.


Honda-Okubo Y.,Vaxine Pty Ltd | Saade F.,Vaxine Pty Ltd | Petrovsky N.,Vaxine Pty Ltd | Petrovsky N.,Flinders University
Vaccine | Year: 2012

Advax™ adjuvant is derived from inulin, a natural plant-derived polysaccharide that when crystallized in the delta polymorphic form, becomes immunologically active. This study was performed to assess the ability of Advax™ adjuvant to enhance influenza vaccine immunogenicity and protection. Mice were immunized with influenza vaccine alone or combined with Advax™ adjuvant. Immuno-phenotyping of the anti-influenza response was performed including antibody isotypes, B-cell ELISPOT, CD4 and CD8 T-cell proliferation, influenza-stimulated cytokine secretion, DTH skin tests and challenge with live influenza virus. Advax™ adjuvant increased neutralizing antibody and memory B-cell responses to influenza. It similarly enhanced CD4 and CD8 T-cell proliferation and increased influenza-stimulated IL-2, IFN-γ, IL-5, IL-6, and GM-CSF responses. This translated into enhanced protection against mortality and morbidity in mice. Advax™ adjuvant provided significant antigen dose-sparing compared to influenza antigen alone. Protection could be transferred from mice that had received Advax™-adjuvanted vaccine to naïve mice by immune serum. Enhanced humoral and T-cell responses induced by Advax™-formulated vaccine were sustained 12. months post-immunization. Advax™ adjuvant had low reactogenicity and no adverse events were identified. This suggests Advax™ adjuvant could be a useful influenza vaccine adjuvant. © 2012 Elsevier Ltd.


Saade F.,Vaxine Pty Ltd | Petrovsky N.,Vaxine Pty Ltd | Petrovsky N.,Flinders University
Expert Review of Vaccines | Year: 2012

Despite many years of research, human DNA vaccines have yet to fulfill their early promise. Over the past 15 years, multiple generations of DNA vaccines have been developed and tested in preclinical models for prophylactic and therapeutic applications in the areas of infectious disease and cancer, but have failed in the clinic. Thus, while DNA vaccines have achieved successful licensure for veterinary applications, their poor immunogenicity in humans when compared with traditional protein-based vaccines has hindered their progress. Many strategies have been attempted to improve DNA vaccine potency including use of more efficient promoters and codon optimization, addition of traditional or genetic adjuvants, electroporation, intradermal delivery and various prime-boost strategies. This review summarizes these advances in DNA vaccine technologies and attempts to answer the question of when DNA vaccines might eventually be licensed for human use. © 2012 Expert Reviews Ltd.


Petrovsky N.,Flinders University | Petrovsky N.,Vaxine Pty Ltd
Drug Safety | Year: 2015

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. © 2015, Springer International Publishing Switzerland.


Li L.,Vaxine Pty Ltd | Saade F.,Vaxine Pty Ltd | Petrovsky N.,Vaxine Pty Ltd | Petrovsky N.,Flinders University
Journal of Biotechnology | Year: 2012

DNA vaccines have evolved greatly over the last 20 years since their invention, but have yet to become a competitive alternative to conventional protein or carbohydrate based human vaccines. Whilst safety concerns were an initial barrier, the Achilles heel of DNA vaccines remains their poor immunogenicity when compared to protein vaccines. A wide variety of strategies have been developed to optimize DNA vaccine immunogenicity, including codon optimization, genetic adjuvants, electroporation and sophisticated prime-boost regimens, with each of these methods having its advantages and limitations. Whilst each of these methods has contributed to incremental improvements in DNA vaccine efficacy, more is still needed if human DNA vaccines are to succeed commercially. This review foresees a final breakthrough in human DNA vaccines will come from application of the latest cutting-edge technologies, including " epigenetics" and " omics" approaches, alongside traditional techniques to improve immunogenicity such as adjuvants and electroporation, thereby overcoming the current limitations of DNA vaccines in humans. © 2012 Elsevier B.V.


Cooper P.D.,Vaxine Pty Ltd | Cooper P.D.,Australian National University | Petrovsky N.,Vaxine Pty Ltd
Glycobiology | Year: 2011

We report a novel isoform of -d-[2 → 1] poly(fructo-furanosyl) -d-glucose termed delta inulin (DI), comparing it with previously described alpha (AI), beta (BI) and gamma (GI) isoforms. In vitro, DI is the most immunologically active weight/weight in human complement activation and in binding to monocytes and regulating their chemokine production and cell surface protein expression. In vivo, this translates into potent immune adjuvant activity, enhancing humoral and cellular responses against co-administered antigens. As a biocompatible polysaccharide particle, DI is safe and well tolerated by subcutaneous or intramuscular injection. Physico-chemically, DI forms as an insoluble precipitate from an aqueous solution of suitable AI, BI or GI held at 37-48°C, whereas the precipitate from the same solution at lower temperatures has the properties of AI or GI. DI can also be produced by heat conversion of GI suspensions at 56°C, whereas GI is converted from AI at 45°C. DI is distinguished from GI by its higher temperature of solution in dilute aqueous suspension and by its lower solubility in dimethyl sulfoxide, both consistent with greater hydrogen bonding in DI's polymer packing structure. DI suspensions can be dissolved by heat, re-precipitated by cooling as AI and finally re-converted back to DI by repeated heat treatment. Thus, DI, like the previously described inulin isoforms, reflects the formation of a distinct polymer aggregate packing structure via reversible noncovalent bonding. DI forms the basis for a potent new human vaccine adjuvant and further swells the growing family of carbohydrate structures with immunological activity. © 2010 The Author.


Petrovsky N.,Vaxine Pty Ltd
Expert Review of Vaccines | Year: 2013

Interview with Jenaid Rees, Commissioning Editor Nikolai Petrovsky is the Chairman and Research Director of Vaxine Pty Ltd, an Australian biotech company that specializes in novel vaccine adjuvants. He also holds the position of Director of Endocrinology at Flinders Medical Centre (Adelaide, Australia), Professor of Medicine at Flinders University, Vice President and Secretary General of the International Immunomics Society and serves on the Editorial Board of our sister journal, Expert Review of Clinical Immunology. He completed his PhD at the University of Melbourne (Victoria, Australia) then moved to Canberra (Australia) where he held conjoint positions at the Canberra Hospital, University of Sydney, Canberra University, Australian National University and the National Health Sciences Centre. In 2004, he moved to his current position at Flinders Medical Centre. His research interests include vaccine adjuvants, autoimmunity and immuno informatics. In 2009, his company Vaxine won the AMP Innovation Award at the Telstra business awards and Australia's coolest company award from Australian Anthill magazine. He has been an investigator for major international diabetes studies including ADVANCE, FIELD and DREAM and is a principal investigator on several large grants from the NIH. He has authored over 140 scientific papers, and his team has developed novel vaccines against influenza, hepatitis B, sting allergy, malaria, Japanese encephalitis, rabies and HIV, in addition to developing the world's first effective H1N1/2009pdm (swine flu) pandemic influenza vaccine. © 2013 Informa UK Ltd.


Patent
Vaxine Pty Ltd. | Date: 2012-06-19

The present invention provides a composition comprising or consisting of inulin particles for use in the reduction or inhibition of inflammation, and/or for treating or preventing inflammatory disease, in a subject. Also provided is a pharmaceutically acceptable composition comprising: particles of inulin; and a substance comprising or consisting of one or more pathogen-associated molecular patterns (PAMPs), or an equivalent kit of parts, and methods and uses of the composition and kit for inducing or modulating an immune response in a subject, such as modulating an immune response to an antigen or allergen and/or as a vaccine. Also provided is a single-dose vaccine composition comprising inulin particles, an antigen and, optionally, an antigen-binding carrier material, and methods and uses of the vaccine.

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