News that one of the potential coronavirus vaccines had at least a 90% efficacy rate was a “victory for science”, said K Srinath Reddy, a cardiologist and president of the Public Health Foundation of India. But it meant little to his country’s 1.3 billion citizens.
“For us, the Pfizer vaccine is more of a scientific curiosity than a practical possibility,” Reddy said.
The need to store the Pfizer/BioNTech vaccine at at least -70C(-94F), with its required cold-chain infrastructure, puts it out of the reach of up to two-thirds of the world’s population, including swathes of south Asia, Africa and even rural parts of the US and South America, according to German logistics company DHL.
Other potential vaccines, such as the Moderna candidate, for which clinical trial results were announced on Monday, will be easier to roll out in warm climates and resource-poor settings.
But for some time now, scientists have been busy developing a range of other ways to deliver vaccines that could bypass the need for expensive cold-chain infrastructure and the fragile glass vials often used to package doses.
Scientists are exploring whether future Covid-19 vaccines could be in the form of inhaled vapours, powders, tablets, oral drops or intranasal sprays, for which the only delivery requirements could be a mailing address.
Almost every vaccine in use comes with a needle. Once jabbed, the body’s immune system usually mounts a response. But a handful of scientists are hoping to harness the immune arsenal of the mucous membranes that line the nose, mouth, lungs and digestive tract, regions typically colonised by respiratory viruses – including Covid-19.
“Over the last 10 or 15 years, it’s been more recognised that protective mechanisms exist at the mucosal surface,” says Dr Christopher Chiu, from the department of infectious disease at Imperial College London. “They are specialised to protect those tissues against infection more quickly, and perhaps more completely, than waiting for the antibodies to come from the blood.”
Exploiting mucosal immunity has potential advantages. Using the oral or nasal passages could help people with needle phobia, and also allow people to vaccinate themselves. “Not having to provide needles and deal with needles … I don’t think you can underestimate how much impact that has on rolling out vaccines to low- and middle-income settings,” said Chiu, who is leading a study designed to assess the viability of inhaled formulations.
Barbara Saitta, an immunisation specialist with Médecins Sans Frontières, said she agreed. “You don’t need a lot of training for medical staff to teach them to open a vial and give it to an adult or child to ingest,” she said. “Injections are more complicated because of the material you need, the needle, and the logistics of sending a vaccine into the field.”
Crucially, some of these alternatives may be able to be stored at room temperature.
Researchers at the Indian Institute of Science in Bengaluru believe their “warm” vaccine against Covid-19 could survive at 100C in powder form, and 70C in a solution – withstanding the searing summer temperatures across India.
“It is still being tested on guinea pigs and may take more than a year to be approved, but if it comes through, you’ll have a heat-stable vaccine that can be turned into a powder and easily transported across the country,” said Reddy.
Vaxart, a San Francisco-based biotechnology company, is testing a tablet-form Covid-19 vaccine to tackle storage temperature problems, which affect even rich countries like the US, said founder Sean Tucker. “If it turns out that we will need to vaccinate people every year, it’s going to be a real challenge,” he added. “A tablet vaccine like ours … we dream that it’s going to be sent by mail, or even drone or some other delivery service, because it is room temperature stable, so you don’t have to deal with the problems with the cold-chain [infrastructure].”
Scientists have taken inspiration from the oral polio vaccine, largely credited with eradicating the disease.
Targeting mucosal tissues has the potential to produce so-called “sterilising immunity”, the complete elimination of infection in the body, reducing transmission “With the intramuscular and systemic vaccines, we know that you can often prevent or reduce the severity of disease but it’s almost never the case that you completely stop the shedding of the virus or pathogen from the site of infection,” said Chiu.
As Dr Scot Roberts, chief scientific officer of Altimmune, a company developing an intranasal Covid-19 vaccine, warned, it is quite likely masks will be here to stay even after the first crop of vaccines hit the market. “And that’s because you may be protected [from the disease], but you’re not protected from spreading the virus,” he said.
There have been hiccups in the quest for non-injectable vaccines. For example, an existing nasal spray flu vaccine has been shown to outperform flu shots in young children, but its performance is muted in adults.
Chiu’s team, which is in the process of securing ethical approval, is hoping to have some preliminary data by spring next year on the aerosolised Oxford vaccine. Meanwhile, Vaxart and Altimmune expect to have their formulations ready for regulatory review by the end of 2021.