There are quite a few options out there for the prospective COVID-19 vaccine recipient these days, but all of them have one thing in common: they come as a shot. But that’s not the only way a vaccine can be delivered – in many cases, it might not even be the best way.
A team of scientists from the University of Houston have announced the development of a vaccine that can be inhaled through the nose. In a paper published this week in the journal iScience, they have shown that when administered to mice, their intra-nasal vaccine is safe and capable of giving rapid immunity against COVID-19.
“[This type of] vaccination can stimulate both systemic [using antibodies] and mucosal [using mucus] immunity,” said Navin Varadarajan, Professor of Chemical and Biomolecular Engineering at Houston and lead author of the paper. “[It also] has the advantage of being a non-invasive procedure suitable for immunization of large populations.”
There are a lot of advantages to a vaccine that can be delivered via the nose, so it’s no surprise that the team aren’t the first to attempt it. A team at the University of Iowa successfully vaccinated mice and ferrets against COVID-19 using a nasal spray back in July, while last month researchers at Lancaster University in the UK chose hamsters as their guinea pigs in another intra-nasal vaccine trial. Over in Finland, researchers are hoping to start human trials soon for yet another intra-nasal vaccine that they say has performed well in pre-clinical testing.
But what is it exactly that makes a nasal spray such a priority? The key lies in how COVID-19 is spread: it’s breathed in through droplets in the air. That means that the nose and mouth are the first points of entry for the virus – if a vaccine could create an immune response in the mucus that protects the nose from minuscule interlopers, then any potential COVID-19 infection could be thwarted before it ever made it into the body.
“Given the respiratory tropism of the virus ... it seems surprising that only seven of the nearly 100 SARS-CoV-2 vaccines currently in clinical trials are delivered intranasally,” wrote immunology professors Frances Lund and Troy Randall in a Science perspective back in July. Neither Lund nor Randall were involved in the Houston vaccine development.
“Advantages of intranasal vaccines include needle-free administration, delivery of antigen to the site of infection, and the elicitation of mucosal immunity in the respiratory tract,” they added.
But the problem with nasal vaccines – and the reason we’ve yet to see an inhalable vaccine on the market – is that it’s harder to get a good immunity response from them, explained Varadarajan.
“[M]ucosal vaccination has been hampered by the lack of efficient delivery of the antigen and the need for appropriate adjuvants that can stimulate a robust immune response without toxicity,” he said.
So an adjuvant – a kind of catalyst added to a vaccine to provoke a stronger response – was what Varadarajan set out to find. Working in collaboration with Xinli Liu, associate professor of pharmaceutics at the University of Houston College of Pharmacy, the team were able to isolate an adjuvant they called NanoSTING.
“We used NanoSTING as the adjuvant for intranasal vaccination and single-cell RNA-sequencing to confirm the nasal-associated lymphoid tissue as an inductive site upon vaccination,” said Varadarajan. “Our results show that the candidate vaccine formulation is safe, produces rapid immune responses - within seven days - and elicits comprehensive immunity against SARS-CoV-2.”
But the advantages of their vaccine aren’t just limited to its success in pre-clinical trials, Varadarajan says – there’s a more human benefit as well. As Western governments celebrate vaccination milestones and prepare to roll out booster shot programs, it’s easy to forget that there are still billions of people across the developing world who have little to no access to immunization. If Varadarajan’s vaccine proves successful, he said, it might just have the edge when it comes to reaching those in need.
“Equitable distribution requires vaccines that are stable and that can be shipped easily,” he explained. “As we have shown, each of our components, the protein … and the adjuvant (NanoSTING) are stable for over 11 months and can be stored and shipped without the need for freezing.”