With many Covid-19 vaccines authorised and billions of doses already manufactured, second-generation vaccine makers are looking for ways to improve on current options. One way is via needle-free administration, which could help the vaccine break through distribution bottlenecks and bolster uptake among people afraid of needles. An oral Covid-19 vaccine has been high on the agenda since the start of the pandemic, and Hong Kong-based DreamTec is looking to cater to that demand.
DreamTec’s oral Covid-19 vaccine has a simple mechanism, says chief scientific officer Keith Wai Yeung Kwong. The company’s vaccine capsule can contain at least a billion Bacillus subtilis spores, which are studded with the receptor binding domain of the SARS-CoV-2 virus. Once the capsule is ingested and survives the corrosive acids in the stomach, the spores would trigger an immune system response in the small intestine.
There are several advantages to DreamTec’s approach, Kwong explains. The spores, and the virus’s receptor binding domain, do not enter the blood stream, which reduces the likelihood of side effects often reported in authorised Covid-19 vaccines that uses a needle and syringe. When it comes to manufacturing, it would not require the same high-level, severe biosafety checks needed when making vaccines that are based on whole viruses. Its spore-based vaccine is also stable in room temperature and can be stored up to six months.
Limited precedence for efficacy
According to the World Health Organization’s list of Covid-19 vaccine candidates, the only other company exploring the potential of a bacteria-based Covid-19 vaccine and is already being tested in humans is Symvivo. However, Canada-based Symvivo’s bacTRL-Spike-1 vaccine works differently. BacTRL carries a plasmid DNA that is taken up by host cells, which then produce antigens to be recognised by the immune system.
Nonetheless, University College Cork vaccines principal investigator Ann Moore is cautious of the potential of bacteria-based vaccines overall. These types of vaccines may induce only one type of immune system response – against the bacteria – and this may not be adequate to trigger the type of response required against a virus, she explains. Also, there is limited efficacy precedence of bacteria-based vaccines, she adds. “It would be great if it works.”
Development started six months ago
DreamTec started work on its spore-based Covid-19 vaccine about six months ago. When a vaccine prototype was developed, it was tested in animal models in collaboration with the Chinese University of Hong Kong. Preclinical data shows the vaccine induced no alarming side effects, Kwong notes. The vaccine also induced neutralising Immunoglobulin G (IgG) and IgM antibodies.
Subsequently, a pilot study recruited nonvaccinated, healthy human volunteers, and ran in alliance with the Hong Kong Metropolitan University. These volunteers took three oral doses of the vaccine, administered 14 days apart. While Kwong declines to detail efficacy data, he says these volunteers’ neutralising antibodies increased significantly from zero.
In the same pilot study, five additional volunteers were recruited who were previously vaccinated with Sinovac’s inactivated virus Covid-19 vaccine CoronaVac, to investigate DreamTec’s vaccine as a booster. These volunteers were given a single dose of DreamTec’s vaccine, around six months after they completed their primary CoronaVac schedule, Kwong says. The result is that these volunteers saw an increase in their neutralising antibody levels, he adds.
Yet one of the longstanding mysteries in Covid-19 vaccine development is what is referred to as correlates of protection: it is still unknown how high neutralising antibody levels should be to correspond to protection, and thus a spike in antibodies may not be high enough to be protective. Kwong says the company is currently working on a manuscript detailing available data so far, to be submitted to a medical journal in the coming days.
Higher dose considered
In the pilot trial, the capsules contained one billion spores, which is overall relatively small, Kwong says. Given the vaccine’s favourable safety profile so far, this dose could be increased to potentially bolster its efficacy potential or reduce the number of doses in forthcoming trials, Kwong notes.
While many vaccine makers have focused on including the whole spike protein in their vaccines, DreamTec’s decision to focus only on the spike’s receptor binding domain was a bid to induce a more specific immune system response. Kwong says the company had explored a version with the full spike protein and found only featuring the receptor binding domain is adequate for efficacy.
Phase I in the cards
There are three things on DreamTec’s to-do list in the coming months. The first is to publish its manuscript, and the second is to secure funding to finance forthcoming trials. Kwong says the firm is in discussions with various governments for a funding boost.
Its third box to tick is to initiate a Phase I trial sometime in Q1 2022, Kwong says. It would recruit at least 30 people to further collect safety data, as well as perhaps study vaccine efficacy at a higher dose. The trial would monitor vaccine efficacy after the second dose, and then after the third dose, for a potential demonstration of its value as a booster.
While the company has clear goals over the next few months and has a unique selling point in its bacteria-based oral Covid-19 vaccine, Kwong is quite aware of the many other vaccines further ahead in the development pipeline. Still, he says: “We are confident we will finish the clinical phase.”