Colaco C.A.,ImmunoBiology Ltd |
Bailey C.R.,ImmunoBiology Ltd |
Walker K.B.,405 Research Boulevard |
Keeble J.,UK National Institute for Biological Standards and Control
BioMed Research International | Year: 2013
Adjuvants were reintroduced into modern immunology as the dirty little secret of immunologists by Janeway and thus began the molecular definition of innate immunity. It is now clear that the binding of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs) on antigen presenting cells (APCs) activates the innate immune response and provides the host with a rapid mechanism for detecting infection by pathogens and initiates adaptive immunity. Ironically, in addition to advancing the basic science of immunology, Janeway's revelation on induction of the adaptive system has also spurred an era of rational vaccine design that exploits PRRs. Thus, defined PAMPs that bind to known PRRs are being specifically coupled to antigens to improve their immunogenicity. However, while PAMPs efficiently activate the innate immune response, they do not mediate the capture of antigen that is required to elicit the specific responses of the acquired immune system. Heat shock proteins (HSPs) are molecular chaperones that are found complexed to client polypeptides and have been studied as potential cancer vaccines. In addition to binding PRRs and activating the innate immune response, HSPs have been shown to both induce the maturation of APCs and provide chaperoned polypeptides for specific triggering of the acquired immune response. © 2013 Camilo A. Colaco et al.
Colaco C.A.,ImmunoBiology Ltd |
Macdougall A.,European Bioinformatics Institute
FEMS Microbiology Letters | Year: 2014
Molecular chaperones are defined as proteins that assist the noncovalent assembly of other protein-containing structures in vivo, but which are not components of these structures when they are carrying out their normal biological functions. There are numerous families of protein that fit this definition of molecular chaperones, the most ubiquitous of which are the chaperonins and the Hsp70 families, both of which are required for the correct folding of nascent polypeptide chains and thus essential genes for cell viability. The groE genes of Escherichia coli were the first chaperonin genes to be discovered, within an operon comprising two genes, groEL and groES, that function together in the correct folding of nascent polypeptide chains. The identification of multiple groEL genes in mycobacteria, only one of which is operon-encoded with a groES gene, has led to debate about the functions of their encoded proteins, especially as the essential copies are surprisingly often not the operon-encoded genes. Comparisons of these protein sequences reveals a consistent functional homology and identifies an actinomycete-specific chaperonin family, which may chaperone the folding of enzymes involved in mycolic acid synthesis and thus provide a unique target for the development of a new class of broad-spectrum antimycobacterial drugs. Sequence comparison of the multiple Mycobacterial GroELs identifies two families with distinguishable by their C-terminal sequences. One of these is specific to mycobacteria and thus presents a novel drug target for anti-mycobacterial agents to treat TB, leprosy and Buruli ulcers. © 2013 Federation of European Microbiological Societies.
Mcnulty S.,ImmunoBiology Ltd. |
Colaco C.A.,ImmunoBiology Ltd. |
Blandford L.E.,ImmunoBiology Ltd. |
Bailey C.R.,ImmunoBiology Ltd. |
And 2 more authors.
Immunology | Year: 2013
Heat-shock proteins (hsp) provide a natural link between innate and adaptive immune responses by combining the ideal properties of antigen carriage (chaperoning), targeting and activation of antigen-presenting cells (APC), including dendritic cells (DC). Targeting is achieved through binding of hsp to distinct cell surface receptors and is followed by antigen internalization, processing and presentation. An improved understanding of the interaction of hsp with DC has driven the development of numerous hsp-containing vaccines, designed to deliver antigens directly to DC. Studies in mice have shown that for cancers, such vaccines generate impressive immune responses and protection from tumour challenge. However, translation to human use, as for many experimental immunotherapies, has been slow partly because of the need to perform trials in patients with advanced cancers, where demonstration of efficacy is challenging. Recently, the properties of hsp have been used for development of prophylactic vaccines against infectious diseases including tuberculosis and meningitis. These hsp-based vaccines, in the form of pathogen-derived hsp-antigen complexes, or recombinant hsp combined with selected antigens in vitro, offer an innovative approach against challenging diseases where broad antigen coverage is critical. © 2013 John Wiley & Sons Ltd.
Agency: GTR | Branch: Innovate UK | Program: | Phase: Smart - Proof of Market | Award Amount: 24.50K | Year: 2013
Vaccines are not yet available to protect against H. Pylori and C. Difficile and the existing therapeutic options available have significant limitations and challenges. Although quoted as significant, the market size for vaccines against these pathogens are poorly defined and the characteristics of a successful prophylactic vaccine product (e.g. production costs, duration of action) are not well established. ImmunoBiology Ltd (ImmBio) intends to establish the market size, intellectual property position and medical need for two potential new vaccines against these pathogens as a necessary first step to establishing full vaccine development projects. Vaccine development activities are both long and costly, therefore it is essential to establish proof of market including commercial viability before significant experimental work is initiated. A full exploitation plan will be established as a part of this project defining the work and costs that will be necessary to bring an effective vaccine to market. Activities will be based on an existing vaccine technology platform ImmBioVax owned by ImmunoBiology and proven to deliver vaccines possessing broad efficacy against pathogens such as N. Meningitidis and Mtb.
Agency: GTR | Branch: Innovate UK | Program: | Phase: Feasibility Study | Award Amount: 146.99K | Year: 2013
Immunisation programmes have proven successful against some of the world’s most deadly diseases but unfortunately vaccines are not available to protect against many existing infections and new vaccine approaches are required urgently to prevent evolving and emerging diseases. For example, vaccines are not available to protect against some strains of bacteria that cause pneumococcal disease (including pneumonia and meningitis). Between 5-10% of all adults and 20-40% of children are carriers and Pneumococcal disease causes more infant mortality than TB, HIV and malaria combined. Existing vaccines are very expensive and cover only a limited number of pathogenic strains. This project will develop an innovative approach for a broadly protective vaccine “PnuBioVax” effective against all disease causing S. pneumoniae strains.
Agency: GTR | Branch: Innovate UK | Program: | Phase: Collaborative Research & Development | Award Amount: 490.00K | Year: 2012
Vaccine immunisation programmes have proven successful against some of the world’s most deadly diseases, eradicating smallpox and on the edge of eradicating Polio. Unfortunately, vaccines are not available to protect against many existing infections and new vaccine approaches are required to stop evolving and emerging diseases. For example, while vaccines protect against some strains of bacteria that cause meningitis, group B meningococcal disease has proved difficult to combat. The Meningitis Research Foundation estimates that there are around 3,300 cases of bacterial meningitis and associated septicaemia every year in the UK and Ireland. No protective vaccine is available against the major B group strains in the UK and infection can often be fatal or lead to significant brain damage and/or limb amputation. This project will develop a new approach to produce a universal vaccine “MenBioVax” effective against all invasive meningococcal disease.
IMMUNOBIOLOGY Ltd | Date: 2010-06-21
The present invention provides an improved method for the purification of a mixture of complexes comprising a stress protein complexed to a peptide or peptide fragment from a source mixture, typically a cell lysate. The method of the invention provides for protein complexes to be purified using ion exchange chromatography based methods, wherein a modified buffer solution is used which results in the purified stress protein complexes being more immunogenic than protein complexes obtained using conventional methodology. The purified complexes can be used to produce improved vaccine preparations which elicit enhanced immune responses in the subjects to whom the vaccine compositions are administered.
Immunobiology Ltd | Date: 2012-05-11
The present invention provides a fusion protein comprising an Fc receptor binding polypeptide and an antigenic polypeptide. The fusion protein may further comprise a linker sequence or hinge portion which joins the Fc receptor binding polypeptide and the antigenic polypeptide. The Fc receptor binding polypeptide typically comprises the CH2 constant domain of a human IgG immunoglobulin. The antigenic polypeptide can be any polypeptide which induces an immune response. Administration of the fusion protein to a subject results in a cytotoxic T lymphocyte response being induced against the antigenic polypeptide provided within the fusion protein. The invention further extends to methods for the treatment of a disease condition in a subject using the fusion proteins of the invention.
Immunobiology Ltd | Date: 2012-03-23
The present invention relates to methods for the production of heat shock protein complexes for use in vaccine compositions. In particular, there is provided a method for increasing the level and immunogenicity of heat shock protein complexes produced in cells by subjecting the cells to specific stress inducing stimuli. The invention further extends to the use of heat shock protein complexes produced according to the methods of the invention in the preparation of vaccine compositions for the prevention and treatment of infectious diseases and cancerous conditions.
PubMed | Murdoch Childrens Research Institute, ImmunoBiology Ltd., University of Melbourne and Norwegian Institute of Public Health
Type: Comparative Study | Journal: Vaccine | Year: 2016
Neisseria meningitidis are common colonizers of the human nasopharynx. In some circumstances, N. meningitidis becomes an opportunistic pathogen that invades tissues and causes meningitis. While a vaccine against a number of serogroups has been in effective use for many years, a vaccine against N. meningitidis group B has not yet been universally adopted. Bacterial heat shock protein complex (HSPC) vaccines comprise bacterial HSPs, purified with their chaperoned protein cargo. HSPC vaccines use the intrinsic adjuvant activity of their HSP, thought to act via Toll-like receptors (TLR), to induce an immune response against their cargo antigens. This study evaluated HSPC vaccines from N. meningitidis and the closely related commensal N. lactamica.The protein composition of N. lactamica and N. meningitidis HSPCs were similar. Using human HEK293 cells we found that both HSPCs can induce an innate immune response via activation of TLR2. However, stimulation of TLR2 or TLR4 deficient murine splenocytes revealed that HSPCs can activate an innate immune response via multiple receptors. Vaccination of wildtype mice with the Neisseria HSPC induced a strong antibody response and a Th1-restricted T helper response. However, vaccination of mice deficient in the major TLR adaptor protein, MyD88, revealed that while the Th1 response to Neisseria HSPC requires MyD88, these vaccines unexpectedly induced an antigen-specific antibody response via a MyD88-independent mechanism.N. lactamica and N. meningitidis HSPC vaccines both have potential utility for immunising against neisserial meningitis without the requirement for an exogenous adjuvant. The mode of action of these vaccines is highly complex, with HSPCs inducing immune responses via both MyD88-dependent and -independent mechanisms. In particular, these HSPC vaccines induced an antibody response without detectable T cell help.