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Inhaled vaccines can induce rapid and strong immune responses in mice and non-human primates

2021-03-11
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In a proof-of-concept study, the researchers demonstrated that the phage-based inhalation delivery system used for vaccines can generate effective antibody responses in mice and non-human primates without causing lung damage. The results of the study indicate that a safe and effective pulmonary delivery system could one day be used for vaccines and therapeutics against respiratory diseases. The results were shown in Med Magazine on December 10.

Co-Senior Research Author Wadi Arap at the Rutgers Cancer Institute in New Jersey said: “This transformation strategy may allow therapeutic agents or vaccines to be delivered more effectively while reducing the incidence of toxic side effects.” In the study, we hope that this work will play a key role in the development of targeted vaccines and therapies to prevent the spread of respiratory infectious diseases, which may be targeted at the current COVID-19 pandemic, especially in people with low levels of service.”
Compared with other routes of administration, especially in the development of vaccines or therapeutics for respiratory infections, pulmonary administration has many advantages because the vaccines reach the site of infection directly. Inhalation-based vaccination is needle-free and minimally invasive, making it particularly attractive for multiple administrations. By achieving a faster onset than needle-based vaccines, it can increase the bioavailability of treatments while reducing potential side effects.
The co-senior researcher explained: “The very extensive and accessible cell surface layer in the lungs is highly vascularized. By avoiding drug-metabolizing enzymes in the gastrointestinal tract and liver, molecules in the entire circulation can be rapidly absorbed at higher concentrations.” Renata Pasqualini of Rutgers Cancer Institute, New Jersey. “Because the lungs are constantly exposed to pathogens in the air, they may have a high immune defense activity, and therefore represent an effective place for immune protection against airborne pathogens.”
Lung delivery can prevent airborne pathogens that cause diseases such as tuberculosis, influenza, Ebola, measles and COVID-19. But this method has not been widely adopted, partly because the basic physiological mechanism is still unknown. Answering this question is critical to designing a universal pulmonary delivery system that is widely used.
In this new study, Arap and Pasqualini designed and verified a safe and effective lung delivery system that can be used in a variety of translation applications and demonstrated how it works. This method involves the use of bacteriophages, viruses that can infect and replicate within bacterial cells. In some types of vaccines, phage particles carrying peptides are used to trigger a protective immune response.
First, the researchers screened and identified a peptide-CAKSMGDIVC-which can effectively pass phage particles through the lung barrier and into the bloodstream. Specifically, when the peptide binds to the receptor α3β1 integrin on the surface of the lung airway lining cells and is internalized by it, the phage particles showing CAKSMGDIVC on its surface will be absorbed by the human body. Inhalation of phage particles displaying CAKSMGDIVC triggers a strong antibody response against phage particles of mice and non-human primates without damaging the lungs.
According to the authors, the new pulmonary delivery system is safe and effective, and has unique advantages in the development of vaccines and therapeutics against airborne pathogens. Phage particles induce a very strong and long-lasting immune response without toxic side effects. Because they cannot replicate in eukaryotic cells, their use is generally considered safe compared to other classic virus-based vaccination strategies. In fact, phage particles have been used as antibiotics and vaccine carriers against multi-drug resistant bacteria.
In terms of actual implementation, phage particles are very stable under harsh environmental conditions. Compared with traditional vaccine production methods, their large-scale production is extremely cost-effective. In addition, unlike conventional peptide-based vaccines that are usually inactivated, the new pulmonary delivery system does not have cumbersome, strict or expensive cold chain requirements for field applications in developing countries. “In addition, phage particles are versatile and can be genetically engineered through standard molecular biology techniques,” Arap said.
Looking ahead, the researchers plan to examine the kinetics of lung transport after multiple doses and study cell-based immune responses. Pasqualini said: “It is important to note that all this work is performed in preclinical models, so we look forward to applying our method to clinical applications, such as pulmonary drug delivery or lung-based vaccination.”

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