Developing an oral Covid-19 vaccine

Vaccinating a global population of nearly eight billion people is no easy task. The Covid-19 pandemic, however, has made this logistically complex quandary a necessity for returning to normal life. 

The need for transport and storage at very low temperatures has made certain candidates, like the mRNA vaccines from Pfizer and Moderna, difficult to distribute in resource-limited parts of the world. In locations without the means to support the cold storage these vaccines need, or those which are very remote, getting jabs into arms becomes far more difficult than it is elsewhere.

Now, Oramed Pharmaceuticals and Premas Biotech have teamed up to develop an oral Covid-19 vaccine which could go some way towards bypassing these logistical issues. 

Together, the companies have merged to form a joint venture focused on the development of Covid-19 vaccines called Oravax Medical, combining Oramed’s proprietary POD oral delivery technology and Premas’ novel vaccine technology.

An oral Covid-19 inoculation could eliminate several of the barriers preventing the rapid, widescale distribution of vaccines – particularly if annual boosters are needed. People may even be able to take the vaccine in their own homes, saving time for medical staff and allowing them to focus their efforts elsewhere.

Oravax’s oral Covid-19 vaccine candidate has a different mechanism of action than the injectable vaccines currently available. 

The mRNA vaccines from Pfizer and Moderna, as well as AstraZeneca’s double-stranded DNA vaccine, all target the spike protein of the virus. 

In order to gain entry into a cell, SARS-CoV-2 uses its spike protein to fuse its own membrane with the cells’ and take it over. It makes sense to target this piece of a virus – prevent it from spiking, and you stop it taking over cells.

The oral Covid-19 vaccine being developed by Oravax is a virus like particle (VLP) triple antigen vaccine. This means it targets three structural proteins – as well as the spike protein (S), the oral vaccine targets the membrane protein (M) and the envelope small membrane protein (E).

Premas co-founder and CEO Prabuddha Kundu says: “We’ve put spike, membrane and envelope together inside our host, which is yeast, to form a particle. What it doesn’t have is nucleic acid, so it’s not infectious and cannot multiply or replicate.”

The oral vaccine’s mechanism of action could potentially make it more efficacious against emerging Covid-19 variants than the current preventatives available. 

While most vaccine candidates are still highly effective at targeting the newer strains of the virus, the S protein could theoretically evolve enough to bypass vaccine-induced immunity – if not altogether, then at least more effectively than it can do right now. 

By targeting the M and E proteins as well as the S, the VLP triple antigen vaccine may be able to protect against S mutations more effectively. Even if it evolves enough to be unrecognisable to the immune system, it has still learned to target the M and E proteins too.

“You can try and disguise yourself by wearing sunglasses, but if your general facial characteristics are known to someone, they will still recognise you,” says Kundu. “In the same way, it would be difficult for mutations to slip past our vaccine candidate.

The oral vaccine could have a number of benefits outside of being easier to distribute in resource-limited settings. Firstly, it could prove to be more eco-friendly than its injectable counterparts.

Oramed CEO Nadav Kidron says: “If you’re looking at vaccinating billions of people, the oral vaccine has a huge advantage as far as waste goes, because of the billions of syringes and pieces of plastic and so on. We don’t get that with the oral vaccine, so I really believe that the future is going to be the oral vaccine.”

Both Kundu and Kidron also theorise that, due to its oral mechanism of action, their Covid-19 vaccine candidate will have fewer side effects than injectable vaccines.

Kundu says: “When you inject a vaccine it goes directly into the bloodstream, bypassing the natural skin barrier we have so that foreign particles cannot go into our blood, and the immune system gets activated. When you take it through the oral route, your gut has a very different and robust immune system, which doesn’t get activated as much as it does when you inject it directly.”

Thus far, the oral Covid-19 vaccine has only been tested in a pre-clinical trial in pigs. The vaccine was able to stimulate an immunoglobulin G antibody response, the most common type of antibody found in blood circulation, as well as an immunoglobulin A (IgA) response. 

IgA is produced primarily in the mucous membranes of the body, although it is found in small amounts in the blood as well and was found in the nose and colon of the pigs.

Moving forward, Oravax aims to enter into a first-in-human trial in Q2 of this year.

Kidron says: “The trial will be quite short. We give the capsules, we measure the blood a few weeks later, and that’s it. It’s not blinded, so as we go through the trial, we’ll be able to see and analyse the data as it comes to us.”