Covid-19 vaccine in a tablet - the next leap in the battle against deadly virus

Many countries lack the cold chain infrastructure or healthcare personnel necessary to administer available doses. PHOTO: AFP

NEW DELHI - "Just to be clear, this is what our (Covid-19) vaccine looks like," Dr Sean Tucker, the chief scientific officer at Vaxart, an American biotechnology firm, said last week while on a Zoom call with The Straits Times.

In his hand was not a vial with a solution that has to be injected into the muscle, the way currently available Covid-19 vaccines are given.

Instead, he showed a single tablet in a blister pack - a tantalising prospect that people could soon pop a Covid-19 vaccine the way they would any ordinary pill.

As countries attempt to outpace the worrying spread of coronavirus with faster vaccination roll-outs, many have been constrained, not just by a limited supply of vaccines, but also their inability to use available doses because they do not have the cold chain infrastructure or healthcare personnel necessary to administer them.

It is this unprecedented challenge in vaccine storage and delivery that San Francisco-based Vaxart hopes to resolve with its tablet vaccine against Covid-19 that could be used across the world without the limitations of needle-based ones.

"You could potentially send it by mail or drone, or, you know, airdrop them. That is the nice thing about having a tablet-based vaccine," Dr Tucker told ST. "There's no learning involved or qualified medical support to take it and it avoids the cold chain. That is a huge advantage." Vaxart's tablet vaccine candidate is currently undergoing Phase II trials.

Covid-19 vaccines in use require some form of cold storage to remain effective, such as the Oxford-AstraZeneca one that has to be stored in conditions between 2 deg C and 8 deg C, and Pfizer's that requires cold storage at minus 70 deg C.

This has proved a challenge in low- and middle-income countries, where a 2018 study found 59 per cent of healthcare facilities lacked reliable electricity to power cold-storage appliances.

It is not just in parts of Africa or India that the lack of such cold-storage facilities has proved to be a hurdle but also in rural parts of the United States and the Australian outback.

"Warm vaccines" currently being developed would be far easier to store and distribute in such places, revolutionising the response to the pandemic in warmer and resource-poor regions.

An encouraging step forward was reported last month when such a vaccine developed by the Indian Institute of Science (IISc) and biotech start-up Mynvax was found capable of triggering a strong immune response in mice and protecting hamsters from the coronavirus.

The vaccine generated antibodies capable of neutralising four Sars-CoV-2 variants, including the highly contagious Delta variant. Researchers, including those from CSIRO, Australia's national science agency, also reported the vaccine remained stable at 37 deg C for up to a month and at 100 deg C for up to 90 minutes.

Dr Raghavan Varadarajan, a professor at IISc and one of the two co-founders of Mynvax, told ST the vaccine will most likely be available in a freeze-dried powder form along with a liquid adjuvant in a separate vial. An adjuvant is an ingredient used in vaccines to help create a stronger immune response.

Both the components can be stored at room temperature and transported easily. They will have to be mixed together to create the vaccine solution for an intramuscular injection. Clinical trials of the vaccine candidate are scheduled to start in six months and a public roll-out is not expected for at least 16 months from now.

Like many other countries, India too has struggled to ramp up its vaccination programme and has been administering an average of four million doses daily. Just under 10 per cent of India's population has been fully vaccinated and the potential need for repeat doses to continue immunity against the coronavirus has accentuated the urgency for vaccines that can be rolled out swiftly.

This is where warm vaccines such as IISc-Mynvax's, which is expected to be sold more cheaply than vaccines currently being used in India, could prove especially helpful in the campaign against Covid-19. Yet, little research has been done to produce warm vaccines globally.

A commentary published in The Lancet in March this year noted that high-income countries were not "really interested in and committed to" developing thermostable vaccines as their refrigeration capacity was never thought to be a limiting factor.

This is why, it said, heat-tolerant vaccines were never prioritised by vaccine developers, industries and funding entities despite their demand from low- and middle-income countries.

It was this overlooked demand for heat-tolerant and easy-to-administer vaccines that Dr Tucker sought to address. Vaxart today specialises in making tablet vaccines, including those against norovirus as well as seasonal influenza.

In May, its Covid-19 vaccine candidate reported encouraging Phase I results, showing higher CD8+ T-cell responses than the Pfizer and Moderna vaccines. CD8+ T cells are a kind of white blood cells that are responsible for generating an immune response. If everything goes well, Vaxart hopes to apply for emergency use authorisation in a year from now.

The firm expects to produce millions - potentially even billions of doses of its vaccine - every year at a price that Dr Tucker described as "cost-effective".

An oral vaccine could also help reduce vaccine hesitancy caused by the reluctance to get jabbed.

Results of a poll commissioned by Vaxart earlier this year reported that nearly 19 million more American adults - about a third of those now refusing to get jabbed - would get vaccinated if they could take a pill instead of getting a shot.

Developing an oral vaccine formulation was a challenge as they do not always work in humans the way they do in animals. The team at Vaxart focused on ensuring best results in humans, even identifying parts of the intestines that are ideal for the tablet to open and maximise impact.

The vaccine deploys a two-step defence mechanism, the first of which is to prompt an antibody response from mucous membranes that form the moist inner lining of certain organs and body cavities such as the nose, mouth, lungs and stomach. If it works, this approach could effectively kill the virus in the upper respiratory system itself, greatly reducing the chances of an individual falling ill from Covid-19.

However, if it fails and an infection takes hold, the CD8+ T-cell response forms the backup defence plan. "Our technology can handle and attack the virus at multiple fronts that are different from the injected vaccines," Dr Tucker said. "This is likely to clear the virus a lot faster."

In the case of the IISc-Mynvax candidate, Dr Varadarajan said there was no challenge involved in ensuring their vaccine remains tolerant to heat, an attribute they wanted when plans for the vaccine were drawn up.

"Had we got several million dollars on day one, we too would have had our vaccine in the market by now," he added, highlighting how many decision-makers at the start of the pandemic believed the coronavirus outbreak was going to be restricted and ultimately controlled with a varied but limited supply of vaccines.

A key challenge for Dr Varadarajan and his colleagues came when they had to choose the right adjuvant solution to rehydrate their freeze-dried vaccine powder and improve its performance. There are not many adjuvants available in the market, with even fewer in the public domain, and a wrong choice of an adjuvant could potentially lead to an unfavourable or sub-optimal immune response.

"The one thing you don't want to have in a vaccine is the enhanced probability of somebody coming down with the disease," he told ST. Their vaccine uses an out-of-patent squalene-in-water emulsion adjuvant. Developing a new adjuvant is a time-consuming as well as difficult and risky business.

While much of global research funding went to newer vaccine technologies such as those that use mRNA, funding in India went primarily to large manufacturers who had tied up with these foreign vaccine developers.

Even today, there are not many warm vaccines in the pipeline. BBC reported this week that Iconovo, a Swedish firm that produces inhaler devices and dry powder formulations for pharmaceutical companies, is collaborating with an immunology research start-up in Stockholm, ISR, which has developed a dry-powder vaccine against Covid-19.

It uses manufactured Covid-19 virus proteins and can withstand temperatures of up to 40 deg C. The company is currently testing its vaccines on the Beta and Alpha variants of Sars-CoV-2.

Ziccum, another Swedish firm, is also testing its technology designed to air-dry existing or future liquid vaccines without limiting their efficacy. The vaccine powder will have to be mixed with a sterile water solution prior to being injected.

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