Game-changer

Likely years away, scientists say a Covid-19 vaccine may be a nasal spray

No needles required!

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Across the globe, thousands of scientists are racing to develop an effective vaccine against Covid-19.

Even if scientists develop a vaccine that works, some people may still opt-out. Communicating the benefits of vaccination, distributing them efficiently, and getting vaccine-hesitant folks on board, are all complex challenges that lie ahead.

A new research development, reported Friday in the journal Science Advances, could solve some of these problems. Scientists created a nanofiber scaffolding technology for vaccines.

In theory, this tech could create a safer and more precise vaccine for Covid-19. The new vaccine involves a nasal spray or spray beneath the tongue — no needles required.

However, vaccine trials usually take years and this development is likely years away. Barring a scientific breakthrough, it likely won't be a matter of months before this is available.

But if this nanofiber tech stands up to these lofty hopes in future experiments, it could change the way we get vaccinated forever.

Study co-author Anita Chong, a researcher at the University of Chicago, tells Inverse the tech has another benefit: more targeted vaccines.

In some traditional vaccines, there are adjuvants, which are agents that can boost a vaccine's effectiveness, but can come with inflammatory side effects, like fever and swelling.

"Our hope is that such technologies that deliver only the parts of the virus that elicits protective immunity without the need for exogenous adjuvants may result in safer, more precise vaccines," Chong says.

"Young children and those that are adverse to needles will benefit from this technology."

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Immune invasion— Chong and her fellow researchers have been developing this nanofiber vaccine system for months but weren't sure whether it induced the targeted immune response or activated T cells — two primary goals of vaccines.

The team used the nanofiber techology to test a specific type of vaccine called a subunit vaccine. Subunit vaccines use a specific portion of the virus to activate an immune response and teach the body to recognize the virus as a whole. Typically, subunit vaccines require adjuvants, which can boost a vaccine's effectiveness.

"The major advantage of subunit vaccines is safety, since they don't involve the replication of live pathogens," said study co-author, Youhui Si, a scientist at the University of Chicago. "On the other hand, to increase their effectiveness, subunit vaccines require adjuvants and repeated doses to induce long-lasting immunity against a disease."

These extra adjuvant add-ins can cause side effects like inflammation, local swelling, fever, and pain.

By testing the novel vaccine platform with fungal and bacterial infections virus in mice, the team found they could induce the targeted immune response and avoid these inflammatory side effects. Importantly, these peptide nanofibers induce immune response in lungs and lymph nodes without requiring adjuvants, priming the immune system against a potential invasion without any nasty inflammation-related side effects.

The most effective delivery method appears to be shooting the active peptide nanofibers tagged with antigens (molecules which stimulate the immune system) up the nose or spraying them under the tongue. No needles involved.

An image of self-assembled peptide nano fibers, which are currently under investigation for engineered vaccines.The Collier Lab

How does this nanotech vaccine work? — The nasal or sublingual spray enables direct activation of the body's dendritic cells, cells that kick off the bodies' innate immune response and line the nose and lungs. The nose is "ground zero" of Covid-19 and the lungs are especially vulnerable because they are laden with ACE-2 receptors that the coronavirus targets.

"We don't know yet which antigens will be most maximally protective against COVID-19," study co-author Joel Collier, a biomedical engineer at Duke University, tells Inverse. "This would let us very precisely target and produce antibodies and T cells that will provide the most protection."

The platform shows great potential, the researchers say, in enabling the ability to fine-tune the immune response and deliver a vaccine directly to affected tissues. The nanofiber scaffolding may also help the immune system recognize and respond quickly to a bodily invader.

"Not only are these routes needle-free, making it easier and more comfortable for people to access, but they can also elicit an immune response in the lungs or mucosal tissues directly," Chong says. "Many infections occur through the oral and respiratory routes, including Covid-19, so being able to trigger that immune response in the right area of the body is very helpful, and could make a vaccine more protective."

We're still a long way off from a Covid-19 nanofiber-based vaccine or nasal spray, but this development is a breakthrough in understanding how this technology influences the body. It may also pave the way for safer, cheaper vaccines against a range of infectious diseases.

"If [vaccine] hesitancy is because of fear of needles or side-effects such as pain at the injection site, then non-needle-based vaccines may reduce people's hesitancy," Collier says. "Overall, however, we are optimistic and hopeful that among the numerous vaccine formulations under intense study right now for COVID-19, more than one will prove to be safe and efficacious."

Abstract: The current paradigm that subunit vaccines require adjuvants to optimally activate innate immunity implies that increased vaccine reactogenicity will invariably be linked to improved immunogenicity. Countering this paradigm, nanoparticulate vaccines have been reported to act as delivery systems for vaccine antigens and induce immunity without the need for exogenous adjuvants or local inflammation; however, the mechanisms underlying the immunogenicity of nanoparticle vaccines are incompletely identified. Here, we show that antigens displayed on self-assembling nanofiber scaffolds and delivered intranasally are presented by CD103+ and CD11b+ lung dendritic cells that up-regulate CD80 and migrate into the draining lymph node (LN). This was accompanied by a nearly exclusive priming and accumulation of antigen-specific TH17 cells occurring independently in both LN and lung. Thus, self-assembling peptide nanofiber vaccines may represent a novel, needle- and adjuvant-free means of eliciting protective immunity against fungal and bacterial infections at skin and mucosal barrier surfaces.
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