Selected ImmBio publications
First-In-Human Study of Immbio’s Novel Pneumococcal Vaccine Pnubiovax Shows Vaccine to be Safe and Immunogenic
Data presented as invited oral presentation at 10th International Symposium on Pneumococci & Pneumococcal Diseases
ImmunoBiology Ltd (“ImmBio” or the Company), a biopharmaceutical company developing next generation anti-infective vaccines based on its proprietary ImmBioVax™ technology, today announces that it has initiated a First-in-Human study of its novel vaccine (“PnuBioVax™”) against the bacterial pathogen Streptococcus pneumoniae.
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.
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.
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.
The development of a vaccine against the human gastric pathogen Helicobacter pylori, the main causative agent of gastric adenocarcinoma, has been hampered by a number of issues, including the lack of a mucosal adjuvant for use in humans. Heat shock proteins (Hsp), highly conserved molecules expressed by both bacteria and mammalian species, possess a range of functions, including acting as chaperones for cellular proteins and the ability to activate innate immune receptors. Hsp complex (HspC) vaccines, containing Hsp derived from pathogenic bacteria, are immunostimulatory without addition of an exogenous adjuvant and can induce immunity against their chaperoned proteins.
In this study we explored in mice the potential utility of a H. pylori HspC vaccine. HspC induced protective immunity against H.pylori without addition of an adjuvant and without the induction of a severe inflammatory response. H. pylori HspC vaccines have the potential to overcome some of the issues preventing the development of a human vaccine against this pathogen.
Vaccine. 2014 Apr 25;32(20):2350-8. doi: 10.1016/j.vaccine.2014.02.051. Epub 2014 Mar 10.
Heat Shock Protein Review: 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 notmediate 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.
The hemagglutinins (HA) of human H1 and H3 influenza viruses and avian H5 influenza virus were produced as recombinant fusion proteins with the human immunoglobulin Fc domain. Recombinant HA-HuFc, secreted from baculovirus infected insect cells as glycosylated proteins of the anticipated molecular weight were oligomers, agglutinated red blood cells, purified on protein A and was used to immunise mice in the absence of adjuvant. Immunogenicity was demonstrated for all subtypes with the sera demonstrating subtype specific hemagglutination inhibition, epitope specificity similar to virus infection and neutralisation. HuFc tagged HAs have potential as candidates for gene-to-vaccine approaches to influenza vaccination.
Heat shock proteins (hsps) are a highly conserved family of proteins, first recognized by their upregulated expression in response to host exposure to raised temperatures. Further study has revealed that they have numerous functions in the cell, primarily as chaperones mediating both the correct folding of nascent polypeptide chains and the dissolution of aggregated protein complexes. The energy requirement for this chaperone activity is provided by the ATPase activity found in most families of hsps and thus the peptide binding capacity is controlled by ATP hydrolysis. The structural consequence of this is that hsps isolated in situ are found complexed to chaperoned peptides (hspCs). Much previous work has implicated hsps in the immune response to pathogens and recent studies have shown that the interaction of hsps with antigen presenting cells, such as dendritic cells (DCs), mediates the integration of the innate and acquired immune responses. This central role for hspCs in immunity is facilitated by their dual function in both innate immunity, with the induction of cytokines and the maturation of DCs mediated by the hsp component, and acquired immunity, with the trafficking of antigens chaperoned in hspCs for antigen presentation by the mature DCs.
The need for an effective TB (tuberculosis) vaccine remains acute, with tuberculosis still one of the major killers worldwide and 3 million new infections annually. We report here on the immune responses elicited by HspCs (heat-shock protein-peptide complexes) isolated from BCG (Bacille Calmette-Guerin) vaccine. These HspCs elicit both the appropriate cellular and protective immune responses required to merit their further development as TB vaccine candidates.