A microscopic image shows vaccine particles with an alumina coating. These particles are fractured to show the coating. Credit: Ted Randolph/University of Colorado Boulder
Researchers from the University of Colorado Boulder in the US have designed a new way to deliver rabies virus (RABV) vaccines which doesn’t degrade at warm temperatures and can release multiple doses following just one shot.
The new technology might soon improve access to rabies vaccination in regions where refrigeration and medical treatment is limited or unreliable.
The findings are presented in a new study in the Journal of Pharmaceutical Sciences.
Rabies infection is estimated to cause about 59,000 fatalities each year, most of which occur in parts of Africa and Asia where the virus is endemic.
Rabies deaths can be prevented by vaccines administered before or soon after exposure. Most rabies deaths are the result of a lack of available vaccines or delays in the timely administration of doses after exposure.
This is because conventional formulations must be kept cold to maintain their stability, which limits access in regions that lack electricity, adequate infrastructure and specialised cold storage.
Patients may not be able to access medical care to receive all 3 to 5 recommended post-exposure prophylactic doses.
To address these challenges, the team formulated a sugar solution containing inactivated rabies virus particles and vaccine components from the existing rabies vaccine RabiVax-S.
When this liquid was sprayed as a fine mist it dried to form a powder of microparticles. The rabies virus proteins are protected within the microparticles’ glass-like texture.
They then used a technique called ‘atomic layer deposition’ (ALD) to further protect the particles with a layer of aluminium oxide (alumina).
“In vivo, alumina coatings gradually erode, eventually releasing the vaccine contents of the inner microparticle in a pulsatile fashion,” write the authors.
“The time at which this release occurs depends linearly on the number of molecular layers of alumina applied; release is delayed by approximately one week for every 50 layers.”
Therefore, a mix of microparticles with protective alumina layers of varying thickness could deliver multiple doses with a single injection.
The formulation was found to be thermally stable for 3 months at temperatures as high as 50°C.
“You can now take these vaccines to places without refrigeration, and even to places that get hot,” says first author Dr Theodore Randolph. “So transportation through rural India or wherever you’re going is no longer a problem.”
When administered to mice, they found that a single injection of the microparticle vaccine powders triggered a stronger immune response than a conventional formulation.
“ALD-coated RABV vaccine microparticles induced IgG [antibodies] and neutralising antibody titres nearly an order of magnitude higher than those generated in response to conventional liquid RABV vaccine formulations,” the authors report.
“Thus, spray-dried and ALD-coated RABV vaccine microparticle formulations offer both thermostability and superior immunogenicity from single vaccine administrations, with the potential for relaxed vaccine cold-chain requirements, antigen-sparing efficacy, and a reduced need for multiple administrations.”
While human trials are still at least a couple of years away, Randolph and co-author Dr Robert Garcea have established a startup to bring the technology to market.