The effort to vaccinate the world against Covid-19 relies on the syringe and needle, using a 19th-century technology to get 21st-century science into the arms of billions. Now the race is on to find alternatives.
Executives such as David Hipkiss sense an opportunity. His firm, Enesi Pharma Ltd. of Oxfordshire, England, is developing a device that painlessly implants a vaccine-imbued tube of sugars smaller than a grain of rice under the skin.
The pandemic has sparked a research-and-development gold rush in vaccines. Developers of novel vaccine-delivery technology hope that they are next, and that the drive to inoculate the planet will shower them with investment dollars and entice big-name partners with deep pockets who can help bring their products to market.
Theirs is a field littered with development misfires and costly gadgets that, for decades, failed to unseat the simple needle, syringe and glass vial. Aside from the occasional nasal spray for flu or sugar lump for polio, the hypodermic needle has been the mainstay of protecting against infectious disease since it was pioneered by a Dublin physician in 1844.
No More Needles
Developers of alternative ways to deliver vaccines use a variety of devices that exploit the body’s immune defenses.
Microneedle patch
Nasal spray
When the patch is applied, microscopic needles infused or coated with vaccine penetrate the skin, causing damaged skin cells to signal the immune system to respond.
Nasal delivery mimics the way the virus typically enters the body and binds to cells. The vaccine uses a harmless viral shell to train the immune system to recognize the invader.
Viral vector
ACE-2 receptor
Respiratory
epithelial cells
Sublingual tablet
Reformulating vaccines so they dissolve slowly under the tongue allows for self-administration and could be a promising alternative to the needle for children.
Another technology uses tiny implants pushed painlessly into the skin that release vaccine as they dissolve.
Reusable actuator
Sublingual fold
Viral vector
ACE-2 receptor
Respiratory
epithelial cells
Microneedle patch
Nasal spray
When the patch is applied, microscopic needles infused or coated with vaccine penetrate the skin, causing damaged skin cells to signal the immune system to respond.
Nasal delivery mimics the way the virus typically enters the body and binds to cells. The vaccine uses a harmless viral shell to train the immune system to recognize the invader.
Reusable actuator
Sublingual fold
Sublingual tablet
Reformulating vaccines so they dissolve slowly under the tongue allows for self-administration and could be a promising alternative to the needle for children.
Another technology uses tiny implants pushed painlessly into the skin that release vaccine as they dissolve.
Viral vector
ACE-2 receptor
Respiratory
epithelial cells
Microneedle patch
Nasal spray
When the patch is applied, microscopic needles infused or coated with vaccine penetrate the skin, causing damaged skin cells to signal the immune system to respond.
Nasal delivery mimics the way the virus typically enters the body and binds to cells. The vaccine uses a harmless viral shell to train the immune system to recognize the invader.
Reusable actuator
Sublingual fold
Sublingual tablet
Reformulating vaccines so they dissolve slowly under the tongue allows for self-administration and could be a promising alternative to the needle for children.
Another technology uses tiny implants pushed painlessly into the skin that release vaccine as they dissolve.
Microneedle patch
When the patch is applied, microscopic needles infused or coated with vaccine penetrate the skin, causing damaged skin cells to signal the immune system to respond.
Nasal spray
Nasal delivery mimics the way the virus typically enters the body and binds to cells. The vaccine uses a harmless viral shell to train the immune system to recognize the invader.
Viral vector
ACE-2 receptor
Respiratory
epithelial cells
Another technology uses tiny implants pushed painlessly into the skin that release vaccine as they dissolve.
Reusable actuator
Sublingual tablet
Reformulating vaccines so they dissolve slowly under the tongue allows for self-administration and could be a promising alternative to the needle for children.
Sublingual fold
Skeptics say that because needles are so inexpensive, abundant and effective, that isn’t likely to change. But the belief among delivery-technology executives and others in the vaccine world is that the pandemic has revealed to all what they have long seen as a false economy. Vaccinating millions isn’t a cheap and easy task when the existing technology requires freezing cold-chain logistics, an army of trained personnel to inject needles, long lines, wasted doses and billions of dollars.
“We’ve got to find a better solution,” said Kate Bingham, a venture capitalist who until December led the U.K. government’s vaccine procurement and deployment program. “Ultimately, we need to be in a position whereby as and when a nasty virus comes along the whole world can get vaccinated.”
Technologies in development for delivering vaccines include Enesi’s dissolving implants, microneedle patches, electrical-pulse systems, nasal sprays and even pills. Some firms are developing their own vaccines against Covid-19, while others are aiming to reformulate some of the dozens already in development or being rolled out world-wide. Some are sitting this pandemic out in the hope of being ready for the next one.
All are in the early to mid-stages of development and clinical testing, suggesting it might be months if not years before they come to market. Big pharmaceutical companies have so far shown limited interest.
If successful, say proponents, these technologies hold out the promise of a world where booster shots against a mutant coronavirus arrive in the mail, vaccines can be kept on a shelf and administered at home, and shots are ferried with ease to the most remote communities on earth.
“There is an absolute renaissance coming in this particular space,” said Mr. Hipkiss.
All vaccines approved for use against Covid-19 require injection into a muscle. As well as being easy to administer, this method has an immunological rationale: It stimulates a response that brings multiple parts of the immune system into play to defend against future exposure.
But there are other ways to stimulate the immune system, such as through the skin, gut or nose, which are among the usual routes foreign invaders take to get into the body. Vaccine-delivery platforms in development attempt to exploit these different pathways.
The skin, for instance, is made up of multiple layers rich in cells that act as sentinels for the immune system. Inoculating people against disease by scratching the skin with needles is an ancient practice. Bifurcated needles that penetrate the skin are a painful memory for U.S. citizens inoculated against smallpox as recently as the 1970s.
Michael Schrader and David Hoey run companies with neighboring facilities in Cambridge, Mass., and similar names that are developing patches studded with an array of microscopic needles to deliver vaccines painlessly through the skin. The patches are housed in applicators that resemble espresso pods. Their ease of use and storage make them ideal for mass vaccination in poor countries without sophisticated healthcare infrastructure and trained medical staff, say Messrs. Schrader and Hoey.
Mr. Schrader, chief executive of Vaxess Technologies Inc., said the possibility that Covid-19 sticks around for years, periodically requiring mass vaccination to prevent new outbreaks, means microneedle technology also has a chance of becoming a useful weapon in governments’ public-health armory.
“Our hypothesis from day one has been that Covid would become endemic and begin to look much more like influenza,” he said. The company’s goal, he said, is to make a combination Covid-19 and influenza patch “that will be mailed to your house every year.” Initial clinical trials of the combination vaccine in humans are planned for early 2022, Mr. Schrader said.
Mr. Hoey, chief executive of Vaxxas Inc., an Australian firm, said the pandemic has meant governments are waking up to the cost of infectious diseases and the need for pandemic preparedness. He doesn’t expect to be able to manufacture his microneedle patches at commercial scale for perhaps three to five years, but thinks he will find a ready market as governments gear up for future public-health crises.
“What you really want is to get the vaccine to the people and not have the people come to the vaccine,” he said.
Other researchers are looking at alternative ways to do away with needles. PATH, a nonprofit global health organization, is working on a way to freeze-dry vaccines that will allow them to be made into a lozenge that dissolves into a gel under the tongue.
“Some people do not like taking shots. Some people do not like coming back for booster shots. So, that’s where alternate technologies would help,” said Manjari Lal, who leads PATH’s work on reformulating vaccines and medicines.
Codagenix Inc., based in Farmingdale, N.Y., is developing a Covid-19 vaccine that is squirted up the nose. The single-dose vaccine, known as Covi-Vac, is undergoing a small, Phase 1 clinical trial in London to assess its safety and the immune response it generates.
| Country | Doses given | Share of population fully vaccinated | Share of population given at least one dose |
|---|
Source: Our World in Data
Jeffrey Fu, the company’s chief business officer, said the pandemic offers new technologies a rare opportunity for advancement, given the world’s hunger for vaccines. “Because of the great urgency behind this, a lot of regulators are helping these device companies advance sooner than they would have if this were more of a traditional vaccine,” he said.
For Dan Mahony, a healthcare fund manager at Polar Capital, a London-based fund manager with around 18 billion pounds, equivalent to $25.5 billion, of assets under management, it isn’t clear if these new technologies will ever get to play as big a role as their developers hope.
People might not like needles but they work well and cost little, he said. Already, makers of Covid-19 vaccines are making improvements that solve some of the distribution challenges: Johnson & Johnson’s Covid-19 vaccine requires one dose instead of two. Pfizer Inc. and BioNTech SE have told U.S. regulators their latest tests on the vaccine they developed jointly show it can be stored safely at minus 20 degrees Celsius, or minus 4 degrees Fahrenheit, after initially opting for minus 70 degrees Celsius.
Mr. Mahony said it isn’t wholly clear if the world will need mass vaccination against Covid-19 for a long time or if governments will choose to protect only their most vulnerable citizens in any new outbreaks, as they do with flu.
“The jury is still pretty out on whether there’s even going to be a market for Covid vaccines after the initial pandemic, and if there is, what does it actually look like?” he said.
Vaccine News
Write to Jason Douglas at [email protected]
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