- Millions of people infected.
- Billions of people affected.
- Trillions of dollars invested.
The world is fighting back.
Stabilitech is part of that fight – you can be too.
The OraPro-COVID-19. A coronavirus vaccine that delivers double immunity via a capsule that may be delivered by post that can be swallowed. No needles, no doctors or nurses, no queues for a vaccine, no risk of cross infection.
The Los Angeles Times’ Ralph Vartabedian says:
Thermally stable, self-administered vaccines in capsule form are the future
The COVID-19 coronavirus pandemic is undoubtedly the most widespread and globally devastating novel virus in recent times. Having jumped from animals to humans, this virus became a pandemic in mere months.
The virus has an incubation period of 10-14 days, during which an infected person is asymptomatic but infectious and it is spread rapidly via human-to-human transmission.
Currently, there is no vaccine.
A vaccine solution for the 21st century
Stabilitech’s OraPro-COVID-19™ vaccine development programme aims to deliver an oral vaccine in just three months. The vaccine has two unique properties: oral capsule administration and double immunity, both systemic and mucosal. With COVID-19 affecting the mucous membranes of the ears, nose and throat, this is vital to its treatment.
OraPro-COVID-19 is a viral vectored adenovirus 5 containing the spike protein DNA from the COVID-19 virus.
- Broad mucosal and systemic immunity– COVID-19 is a mucosal virus, less than 1% of patients have it in their blood. While needle-based vaccines are focused on systemic immunity, a dual-focused vaccine focused on both the mucosal and systemic immunity is likely to be more effective.
- Oral administration and speed to the last dose– Stabilitech is the only company that can produce a thermally stable capsule vaccine that does not require a healthcare professional for administration. This means that rapid vaccination of millions of people will be possible at the speed of production of the capsules. By comparison, refrigerated vaccines that require injection result in slow mass immunisation and are logistically challenging.
- Thermal stability– meaning logistics are simple and the vaccine does not need refrigeration. It can be posted to patients to administer in their own home.
- Minimal risks to the general population and healthcare professionals– oral dosing using thermally stable capsules removes the need for patients to have physical contact with other members of the general population and healthcare professionals, adhering to social distancing guidelines. Additionally, needle-stick injuries are eliminated.
- Manufacturing – based on our Zika study in non-human primates, administration via the GI tract’s mucosal lining showed that we did not need a high dose of vaccine. Potentially, this may mean that we will get hundreds or even thousands more doses per manufacturing run. In a pandemic such as COVID-19 where 60% of the world’s population needs immunity this may be one of the most significant benefits.
OraPro-COVID-19 – the journey so far
The battle for double immunity
To protect against respiratory infections, vaccines should induce both mucosal and systemic immune response. Parenteral immunisation, such as needles or electroporation, generally fail to induce mucosal immunity and mucosal delivery often results in poor systemic immunity. Mucosal antibodies can readily neutralise invading viruses at the luminal site of the epithelial layer and prevent entry into host cells. Such an immune exclusion effect is mainly mediated by secretory immunoglobulin A (SIgA), which is induced by mucosal but not parenteral immunisation.
Delivering the world’s first oral vaccine
Stabilitech’s OraPro platform technology enables the development of vaccines that can infect the epithelial cells in the gastrointestinal (GI) tract and therefore generate both a mucosal and systemic immune response.
Overcoming the limitations of viral vectors
Without Stabilitech’s OraPro platform, getting an oral vaccine into the small intestine where it can deliver its cargo is almost impossible.
Viral vectors are thermally unstable and must be maintained below -50°C. They are easily killed and rendered inefficacious in the stomach where they sit at 37°C for several hours before being transported to the small intestine.
The OraPro platform enables adenovirus viral vectors to remain thermally stable in temperatures up to +50°C for extended periods or two years at +25°C. This technology permits a new generation of oral vaccines.
OraPro uses a non-replicating viral vector to deliver the COVID-19 spike protein DNA to the mucosal cells in the GI tract, ensuring no anti-vector immune response. A strong anti-vector response would inhibit the re-use of the same vector for second doses, if required, and limit further vaccine candidates. The lack of anti-vector immune response unlocks a ‘plug and play’ aspect for OraPro. Only the infectious disease antigen is changed between developments, enabling a large amount of manufacturing, regulatory and safety continuity and a faster route to market.
OraPro utilises adenovirus type 5, a non-integrating virus and one of the most well characterised viral vectors. Additional gene deletions are performed to ensure the recombinant adenovirus (rAd) vector is non-replicating, further enhancing safety.
Using the OraPro platform for COVID-19 vaccine development
The current COVID-19 outbreak is an ideal application for OraPro technology.
Studies examining a recombinant adenovirus vaccine expressing the MERS-CoV spike protein(rAd/Spike), illustrated superior immune responses, capable of halting infection with viruses pseudotyped with MERS-CoV spike protein (Kim et al., 2019: PLoS ONE; 14(7): e0220196). However, recombinant adenoviruses such as those used in these studies are thermally fragile and must remain within strictly controlled temperature environments to maintain efficacy. They would simply not survive oral delivery without the OraPro platform.
A rAd/Spike construct is likely to be a good candidate for a successful vaccine against COVID-19.
There is increased pressure to find a vaccine for COVID-19 as mounting infection rates, strains on health systems and impacts on the global economy continue to escalate.
Stabilitech’s technology has an extremely rapid production timeline. If all steps proceed uninterrupted, the first batch of vaccine could be released within 12 weeks from having the nucleic acid construct for the antigen.
The benefits of the OraPro-COVID-19 vaccine:
- Enhanced immunity – As orally delivered adenoviruses infect the cells of intestinal lumen – a mucosal surface – it is highly likely that a mucosal response will be elicited. This is advantageous when treating respiratory infections, as the \within the bronchi and alveoli would also be primed against the antigen. The mucosal immunity would work alongside systemic immunity, producing double protection.
- Speed to the last dose – OraPro utilises well known adenoviral vector technology to generate its vaccine active product. Proprietary formulations are then added to provide thermal robustness and the doses are prepared. We estimate that with an uninterrupted vaccine production campaign, approximately one million doses could be produced from a small-scale contract research organisation (CRO) approximately 12 weeks from obtaining the antigen coding nucleic acid.
- Speed of patient adoption – oral vaccination through a single-dose, means the vaccine can be quickly delivered through the mail to the patient’s home.
- Reduced chance of transmission – capsules enable patients to self-administer the vaccine, which removes the need to meet with a healthcare professional in person. This reduces the risk of spreading the virus.
- Regulatory approval – adenovirus has been administered orally to millions of people and is generally considered safe. From a regulatory perspective, this will likely shorten the pathway to marketing approval.
- Significant cost savings:
- No healthcare professional cost – as the vaccine can be orally administered at home.
- Simplified distribution logistics – a thermally stable vaccine reduces the cost of distribution by removing the need for temperature-controlled or cold chain logistics.
- Thermally stability – 50% of vaccines, around 151 million doses, are wasted each year due to temperature excursions. This is a particular challenge for developing countries, however, an audit conducted in the US by the Office of the Inspector General for the Vaccines for Children Program (VFC) discovered that improper temperature storage of vaccines is also a problem for the industrialised world. During the two-week study period, 76% of healthcare providers audited exposed their vaccines to inappropriate temperatures for at least five cumulative hours.
- Low production costs –the cost per finished dose once in full production is estimated at less than $0.25.
- GMP defined – good manufacturing practice has already been defined following proof of concept of the OraPro-Zika vaccine™. The viral vector can be added at the fill/finish stage into the capsules ready for administration.
Proof of concept complete
The proof of approach for OraPro-COVID-19 has already been completed with the development of an oral vaccine for Zika, OraPro-Zika™, funded by the UK Department of Health through Innovate UK. OraPro-Zika has been shown to elicit protective efficacy in both mice and non-human primates in response to the wild type Zika virus. The vaccine delivers a payload of Zika antigen-expressing DNA to the cells of the intestinal lumen, resulting in the expression of the protective antigenic protein and an effective immune response.
Non-human primate challenge
OraPro-Zika was manufactured in the UK and shipped (without a cold chain) to Brazil for pre-clinical testing in non-human primates.
Subjects were tested and confirmed Zika negative before commencing the programme (pre-OraPro-Zika vaccine). 21 days after vaccination (or placebo), an aggressive live Zika challenge was administered intravenously and the subsequent Zika infection was recorded (post-ZIKV exposure).
The ‘post-ZIKV exposure’ results clearly show that the immunity gained from OraPro-Zika appears as effective at halting a Zika virus infection as the natural immunity of subjects who have previously been infected with a whole Zika virus.