Scientists have developed an inhalation delivery system for vaccines that elicits powerful immune responses in mice and non-human primates, without causing lung damage, a breakthrough that may lead to new therapies for respiratory diseases like Covid-19.
The findings, published in the journal Med, suggest that a safe and effective pulmonary delivery system could be developed for vaccines and therapies against pathogens such as the new coronavirus.
“This translation strategy potentially allows for more effective delivery of therapies or vaccines while reducing the possibility of toxic side effects,” said study co-author Wadih Arap of the Rutgers Cancer Institute in the US.
According to the researchers, this mode of administration of the vaccine has many advantages over other routes, in particular for the development of vaccines against respiratory infections, since the therapy reaches the site of infection directly.
Inhalation vaccination does not require needles and is minimally invasive, they said, adding that it is especially attractive for administering multiple doses.
The researchers said that this method improves bioavailability and also reduces potential side effects by achieving a rapid onset of action.
Scientists believe that pulmonary administration could protect against airborne pathogens that cause diseases such as tuberculosis, influenza, Ebola, measles, and Covid-19.
However, they said this approach has not been widely adopted, in part because the underlying physiological mechanisms remain largely unknown.
They said answering this question is critical to designing a general pulmonary delivery system for widespread use.
In the new study, the researchers designed and demonstrated a safe and effective pulmonary delivery system.
They said the approach involves the use of phages, viruses that can infect and replicate within bacterial cells.
In certain types of vaccines, they said that phage particles that carry small proteins, or peptides, are used to trigger protective immune responses.
First, the researchers searched for and identified a small protein, CAKSMGDIVC, that could transport phage particles across the lung barrier and into the bloodstream efficiently.
They found that inhaled administration of phage particles displaying CAKSMGDIVC elicited a robust antibody response against phage particles in mice and non-human primates, without damaging the lungs.
According to the scientists, the new pulmonary delivery system is safe and effective, and has unique advantages for the development of vaccines and therapies against airborne pathogens.
They said that the phage particles induce very strong and sustained immune responses, without producing toxic side effects.
Since they do not replicate within eukaryotic cells, their use is generally considered safe compared to other classical virus-based vaccination strategies.
In terms of practical implementation, the study noted that phage particles are highly stable under harsh environmental conditions, and their large-scale production is extremely cost-effective compared to traditional methods used for vaccine production.
Unlike conventional vaccines that are often inactivated, the new pulmonary delivery system does not have cumbersome, strict, or expensive cold chain requirements for field applications in the developing world, the scientists said.
“In addition, phage particles are versatile and can be genetically manipulated using standard molecular biology technology,” Arap said.
Next, the researchers plan to examine the kinetics of pulmonary transport after multiple doses and investigate cell-based immune responses.