Oral and Nasal Covid-19 Vaccines Hit Clinical Testing

oral vaccine covid 19

Oramed’s jab-free oral Covid-19 vaccine is one of many in the form of pills, powders, or sprays that may hit the market in the next few years, which could dramatically expand vaccine rollout and uptake.

An Israeli team is preparing to start trials of what could be the first Covid-19 vaccine pill. The vaccine consists of a virus-like particle, essentially a virus which is almost identical to SARS CoV-2 on the outside but contains no genetic material and cannot reproduce inside the body. 

According to the vaccine’s developers, the US- and Israel-based biotech Oramed Pharmaceuticals and its Indian partner Premas Biotech, the vaccine is able to stimulate immunity against a wider range of Covid-19 antigens than vaccines currently on the market do. 

Like all marketed vaccines, Oramed’s pill targets the spike protein that allows the virus to enter human cells, and which often mutates to give rise to potentially dangerous viral variants. But the vaccine also targets two other proteins on the surface of the virus that mutate more slowly in order to better protect against viral variants. All being well, their candidate could go through approvals in the first half of next year.

Prabuddha Kundu, the co-founder and Managing Director of Premas, said that the vaccine triggered the production of antibodies against all protein antigens in preclinical studies. “This has a huge potential against the viral strains that have the spike protein mutating. With the three antigens, we believe that our vaccine would be more effective and the data is being generated.” 

How many pills of Oramed’s oral vaccine would be needed to build an effective immunity against Covid-19 will be clarified during the upcoming clinical trials, Oramed CEO Nadav Kidron added. Proper dosing, according to the scientists, is also the biggest challenge they currently face.

Currently, there are at least 10 Covid-19 vaccines in clinical development worldwide that are delivered to the nose, mouth, or gut. Alongside the Oramed-Premas team, many developers see a major potential advantage in stimulating immunity in the mouth, nose, gut, and other organs lined with mucous membranes. Since these are the most common points of entry of the Covid-19 virus, creating a strong local immune response there could nip the infection in the bud.

One well-known player is the University of Oxford, which launched a phase I trial of an intranasal formulation of AstraZeneca’s approved Covid-19 vaccine Vaxzevria in March. But the path through clinical testing has already proved difficult for another vaccine contender: the US company Altimmune shuttered its nasal spray Covid-19 vaccine in June after it was found to be less effective than current vaccines in a phase I trial. 

Boosting immunity against respiratory infections via the nose and gut has several precedents, with one example being intranasal flu vaccines. Another is Respivax, a cocktail of bacterial antigens in the form of a small pill marketed by the Bulgarian firm Bul-Bio to prevent bacterial infections. 

Tzvetelina Stefanova, the Production Director of Bul-Bio, said that Respivax has been shown to produce a strong mucosal immunity against broad groups of pathogens. Based on that experience, she added that approaching oral Covid-19 vaccines through the lens of mucosal immunity should be a priority for researchers and companies.

There’s a major additional perk to oral and nasal Covid-19 vaccines: simple supply logistics. Shots in general — and especially messenger RNA vaccines, which are particularly unstable and often require deep freeze for transportation — present a formidable logistics challenge. This is particularly the case in the developing world, where both trained medical personnel and proper transportation infrastructure are in short supply. The price and speed of Covid-19 vaccine production are also major factors driving global inequality.

The advantages of a single-use dry powder version of a vaccine are many,” said Johan Wäborg, CEO of the Swedish biotech Iconovo, which is working on a Covid-19 vaccine in the form of a nasal powder. These include “cost reduction, logistical improvements with no cold chain, easier administration, in the long run probably self-administration, [and] no risk of handling needles that lead to hazardous waste.

In Europe, over 57% of adults are now fully vaccinated against Covid-19 and over 70% have received at least one dose. However, vaccine hesitancy is a major remaining obstacle to further coverage in developed countries.

One element of vaccine hesitancy that hasn’t been discussed in great detail is that of needles,” Jose Ordovas-Montanes, an immunologist at Harvard University, told me. “While a quick jab may seem harmless to many, for others it can serve as a significant barrier to receiving a vaccine.

In areas with higher coverage, the early Covid-19 vaccines have decreased hospitalizations and, to a lesser degree, infections. The next generation of Covid-19 vaccines is likely to be better targeted and to focus more on convenience, ease of manufacture, and transportation as well as augment immune responses and reduce side effects.

In terms of the future of Covid-19 vaccines, what we are really striving for on both the tissue and societal scales are vaccines that work locally and sustainably,” Ordovas-Montanes said. 

“Our ideal vaccines would stimulate local and long-lasting immunity in the key tissues of relevance — namely the nose and lung where the body is likely to make key first decisions in its interaction with the virus — and also in our society where we need to identify formulations that work for each community and serve as sustainable solutions.”

Cover image from Anastasiia Slynko. Table from Jonathan Smith.

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