The Native Antigen Company Limited Public Funding

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At the start of 2016, Zika virus hit the headlines with an outbreak in Brazil far larger than any seen before, causing a huge rise in the number of children born with smaller than average heads and other abnormalities. As this virus is relatively recent, there are very few diagnostic methods of detecting the disease it causes, and most of the currently available ones can’t tell the difference between Dengue Fever and Zika. We intend to use our unique Zika virus products to develop a quick and easy test for Zika virus that does not show a false positive reaction with Dengue virus. By developing a test that works like a pregnancy test, we hope to provide reassurance to millions of mothers-to-be who live in tropical countries and want to start a family without the fear of birth defects.

Diagnostic tests are a vital component of disease diagnosis and vaccine research. For any test, the important parameters are sensitivity (i.e. the ability of the test to correctly identify a positive sample) and specificity (i.e. its ability to discriminate correctly between different diseases). Most diagnostic tests are simple plate-based assays or pregnancy test-type assays – cheap and easy to run in most labs or GP surgeries, but often suffer from poor sensitivity and specificity. For example, tests for Chlamydia pneumonia can be false positive if genital Chlamydia trachomatis is present, and dengue virus tests come up positive for West Nile virus and tick-borne encephalitis. Plaque reduction neutralisation tests (PRNTs) get around these cross-reactivity problems, and are currently the gold standard diagnostic test, but they use live pathogens that are often extremely hazardous to handle and can take up to 10 days to perform. This means they can only be done in rare specialised laboratories and have a high cost per test. PRNTs are also used in vaccine research, where the number of neutralising antibodies is used as a measure for how efficacious a vaccine is. Having to perform these tests in high biocontainment facilities raises the cost of vaccine research and the speed to develop a successful vaccine. Our novel test is designed to provide the specificity and sensitivity of a PRNT, but with 100% safe reagents and taking only 1 day to perform. We believe this would be of great help to improve diagnosis for many human and animal diseases and to enable and enhance vaccine research into hazardous pathogens.

The global market for therapeutic monoclonal antibodies (mAbs) has become the fastest growing segment of the pharmaceutical industry. The antigen is the lynchpin of therapeutic mAb development, so understanding, controlling and engineering antigens to increase immunogenicity is of vital interest to the pharmaceutical and diagnostic industry. Despite the success so far, up to 25% of all candidate antigens fail to elicit an immune response and thus cannot yield effective mAbs. The failure rate is particularly high in the cancer market, where the key antigens are naturally modified by glycosylation in a manner not achievable using current antigen production technology. To overcome this key limitation, we propose to take a novel approach which would display peptides genetically linked to the surface of enveloped virus like particles. This would lead to the peptide of interest mirroring its native glycosylation state to deliver a high degree of specificity, markedly increasing the affinity of the resultant antibody to the native protein. This will allow the generation of optimised mAbs, generating novel therapeutics against previously impossible targets. Following a successful proof of concept, the technology platform will initially be focused toward antigens to be used in production of mAbs for cancer therapy and then to candidate viral antigens such as HIV and CMV, where vaccine development has proved notoriously difficult.

The Native Antigen Company (NAC) proposes to examine the technical feasibility of developing a novel mammalian cell expression system which would overcome the current barriers to producing suitable antigens from enveloped viruses for use as vaccine candidates. Our innovative approach would centre on the provision of pure Virus-Like Particles (VLPs) containing the antigen of interest, in high concentration, embedded natively in the lipid membrane. As a target for the feasibility project NAC will focus on a human CMV antigen. This infection represents one of the highest healthcare burdens resulting from a lack of a suitable vaccine.

Clostridium difficile infection (CDI) is a major cause of morbidity and mortality in economically developed countries. CDI is primarily linked with hospital admission and prior antimicrobial treatment. Although significant advances have been made to reduce incidence, a number of hypervirulent and highly transmissible strains have recently emerged. Resultant healthcare challenges are compounded as widespread use of antibiotics encourages both the emergence of resistant strains and reoccurrence of infection, especially in the elderly. The financial impact of hypervirulent strains on the healthcare system is substantial ($1.1 billion/year in the USA). Assuming a European Union population of 457 million, the potential cost is estimated to be €3000 million/year, and without targeted treatment is expected to double over the next four decades. In response, pharma focus is shifting toward the development of vaccines for single “catchall” immunisation. However, due to inability to source highly pure native (representative of the true functionality) toxins, vaccine researchers cannot fully determine how antibodies may be cross-protective and whether there is cross reactivity between strains. NAC will aim to use its current expertise in native antigens to isolate and purity the native toxin strains for the first time and at a yield which meets demand. There are no known commercial suppliers of such toxins. We are a newly formed biotech company (November 2010) that specialises in the manufacture of high value infectious disease antigens for the vaccine and diagnostic Industry. NAC now trades with over 30 companies worldwide with exports representing over 85% of its business. NAC has an agreement with a pharmaceutical company to support this proof of concept by evaluating project development progress. This company will become an adopter to provide early revenue. There are no market restrictions placed upon NAC to prevent it selling to the open market.

Early detection of infectious disease offers the greatest opportunity to contain potential outbreaks, save lives and decrease the economic burden of healthcare. Rapid diagnostic test kits are one of the most effective ways to achieve this, allowing health care workers or members of the public to identify disease in the community. These tests, usually in the form of strips or cassettes, provide a visual indication if a specific disease is present. A vital component of a test kit is the disease ‘antigen’ which is a copy of the target disease that is able to detect antibodies in human samples. Manufacturing these antigens is very challenging using standard techniques and synthetic antigens are often very poor representatives of the real pathogen. For these reasons there are many diseases for which there are no suitable rapid test kits or if they exist, they are generally of poor accuracy. The Native Antigen Company (NAC) specialises in addressing the need for rapid diagnosis by producing high quality, authentic antigens. The company’s unique skills and capabilities are drawn from its early connection with the vaccine industry. We are now at the stage of seeking to expand our level of research expertise to produce antigens for emerging markets which are more challenging to manufacture and have a high impact of improving healthcare. One example of this is Dengue Fever, an infectious tropical disease caused by the dengue virus. Unless detected early and controlled, the disease may manifest into the life-threatening dengue hemorrhagic fever (DHF). DHF is now endemic in more than 110 countries and severe forms of the disease carry a mortality of up to 26%. Producing a suitable antigen which will, for the first time, offer a simple cost effective means to accurately detect DHF at the community level will require new innovation. This project will exemplify a new platform opportunity for the company and enable us, in the future, to address other pathogens.