OraPro-COVID-19™

The COVID-19 Corona virus has recently jumped from animals to humans. It is believed to have an incubation period of 10-14 days, during which an infected person is asymptomatic but infectious. This coronavirus is spread via human-to-human transmission. Currently there is no vaccine.

21st Century vaccine solution

Stabilitech’s OraPro-COVID-19 vaccine development aims to deliver in 3 months an oral vaccine with two unique properties, capsule administration and broad mucosal and systemic immunity:

  • Broad mucosal and systemic immunity – OraPro-COVID-19 is a viral vectored adenovirus 5 containing the spike protein from the COVID-19 virus.
  • Oral administration and speed to last dose – Stabilitech is the only company that can produce a thermally stable capsule vaccine which does not require a healthcare professional for administration. This means that rapid vaccination of millions/billions 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 – means logistics are simple and the vaccine does not need refrigeration, it’s just like shipping aspirin.
  • Minimises risks to 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 with healthcare professionals in order to be immunised. They can be delivered by post. Additionally, needle-stick injuries will be eliminated.

Background

Ideally, vaccines for protection against respiratory infections should induce both a mucosal immune response and a systemic immune response. However, parenteral immunisation generally fails to induce mucosal immunity and mucosal delivery often results in poor systemic immunity. In particular, mucosal antibodies can readily neutralise invading viruses at the luminal site of the epithelial layer and prevent their entry into host cells. Such an immune exclusion effect is mainly mediated by secretory IgA (SIgA), which is effectively induced by mucosal but not parenteral immunisation.

Oral approach

A viral vectored oral vaccine will infect the epithelial cells in the GI tract and thus should be able to generate both a mucosal and systemic immune response.

Stabilitech’s OraPro platform overcomes limitations of viral vectors

Thermal stability

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 have to be maintained at -80°C. They are easily killed and rendered inefficacious in the stomach where they sit at 37°C for several hours before transport to the small intestine.
The OraPro platform enables adenovirus viral vectors to remain thermally stable up to +50°C for 2 years. This permits a new generation of oral vaccines.

Non-replicating vector

OraPro uses a non-replicating viral vector to deliver the COVID-19 DNA to cells in the GI tract. This ensures that no anti-vector immune response is generated. A strong anti-vector response would inhibit the re-use of the same vector for second doses (if required) and therefore limit other new vaccine candidates. This lack of anti-vector immune response unlocks a plug-and-play aspect for OraPro, where only the infectious disease antigen is changed between developments, enabling a large amount of manufacturing, regulatory and safety continuity.

Non-integrating vector

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 vector (rAd) is non-replicating to further enhance safety aspects.

Suitability of OraPro platform for COVID-19 vaccine development

The current COVID-19 outbreak would clearly be a suitable application for OraPro. Studies examining a recombinant adenovirus vaccine expressing the MERS-CoV spike protein(rAd/Spike), illustrated superior immune responses capable of halting infection with virus 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 have to remain within strictly controlled temperature environments to maintain efficacy and would not survive oral delivery without the OraPro platform.
Thus a rAd/Spike construct is likely to be a good candidate for a successful vaccine against COVID-19.
The extremely rapid timeline to produce the first doses of vaccine using Stabilitech’s technology is another factor making it an ideal fit for the present outbreak. 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.

Benefits of OraPro-COVID-19 vaccine

  • Enhanced immunity – As orally delivered adenovirus infects the cells of intestinal lumen, a mucosal surface, it is highly likely that a mucosal response is elicited. This would have tremendous advantages to respiratory infections, as the SIgA within bronchi and alveoli would be primed against the antigen.
  • Speed to 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 1 million doses could be produced from a small scale CRO approximately 12 weeks from obtaining the antigen coding nucleic acid.
  • Speed of patient adoption – Oral vaccination means a capsule can be provided directly to the patient.
  • 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 – adenovirus has been administered orally to millions of people and is generally considered safe. From a regulatory perspective, it may be that this will shorten the pathway to marketing approval.
  • Significant cost savings:
    • No healthcare professional cost – eliminating the need for a healthcare professional to administer the vaccine dramatically reduces costs. Additionally, it removes the risk of needle stick injury.
    • Simplified distribution logistics – thermally stable vaccine reduces the cost of distribution by removing the need for temperature-controlled logistics.
    • Thermally stability – 50% of vaccines are wasted each year due to temperature excursions, which amounts to around 151 million doses. This is particularly a 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 the healthcare providers that were audited exposed their vaccines to inappropriate temperatures for at least five cumulative hours.
    • Low production costs – we have estimated that the cost per finished dose once in full production will be in the region of < $0.25.

Proof of concept exists with Stabilitech’s OraPro-Zika vaccine

Proof of the approach 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 to direct challenge the wild type Zika virus. The vaccine delivers a payload of zika antigen expressing DNA to the cells of the intestinal lumen, whereupon the protective antigenic protein is expressed and subsequent immune response elicited.

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 prior to 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.

Manufacturing

The GMP process will follow the same path as our Zika vaccine. The viral vector will then be fill/finished into capsules ready for administration.