Innovative mucosal nanocarrier systems for enhanced immune response against respiratory pathogens

Area of Science:

• Nanotechnology
• Immunology
• Vaccinology

Background:

• Pulmonary vaccination faces challenges due to the pulmonary surfactant barrier and inefficient delivery to alveolar macrophages.
• Alveolar macrophage-derived vesicles offer a biomimetic approach to overcome these limitations.

Purpose of the Study:

• To develop a nanovaccine platform using biomimetic alveolar macrophage membrane vesicles (AMVs).
• To engineer AMVs to address lung-specific barriers and enhance intracellular vaccine delivery.
• To evaluate the immunogenicity and protective efficacy of the nanovaccine against respiratory pathogens.

Main Methods:

• Engineered AMVs with an Antigen Capture and Cytosolic Delivery System (ACCDS) for pathogen binding and endosomal escape.
• Incorporated Poly(I:C) to activate Toll-like receptor 3 (TLR3) and RIG-I/MDA5 signaling pathways.
• Assessed delivery performance, cellular uptake, innate immune responses, T cell differentiation, and protection in respiratory infection models.

Main Results:

• AMV-ACCDS-Poly(I:C) demonstrated superior delivery in the pulmonary surfactant environment and preferential uptake by alveolar macrophages.
• Achieved dual innate immune activation, leading to enhanced IFN-β and IL-18 responses.
• Conferred complete protection against lethal influenza and pseudorabies virus challenges and reduced Mycoplasma pulmonary burden.

Conclusions:

• Biomimetic AMVs offer a promising strategy to overcome pulmonary vaccination barriers.
• This membrane-based nanovaccine platform shows potential for effective mucosal immunization against diverse respiratory pathogens.