Inhalable SARS-CoV-2 Mimetic Particles Induce Pleiotropic Antigen Presentation.

Area of Science:

• Immunology
• Nanotechnology
• Vaccine Development

Background:

• Coronavirus disease 2019 (COVID-19) poses a global health threat, exacerbated by vaccine hesitancy and distribution challenges.
• Injectable vaccines face limitations including cold storage requirements, needle phobia, and potentially lower mucosal immunity.
• Alveolar macrophages are crucial for lung immunity and early COVID-19 pathogenesis, making them ideal targets for novel vaccines.

Purpose of the Study:

• To develop and characterize inhalable coronavirus mimetic particles (CoMiP) for delivering nucleic acid-encoded viral antigens.
• To design CoMiP that mimic SARS-CoV-2 virion structure for efficient targeting and uptake by alveolar macrophages.
• To evaluate the in vitro transfection efficiency and in vivo immunogenicity of CoMiP.

Main Methods:

• CoMiP were engineered with a macrophage-targeting glycosaminoglycan coating and an endosomolytic peptide envelope.
• Particles were designed to encapsulate nucleic acid cargo encoding viral antigens.
• In vitro studies assessed CoMiP transfection of macrophages and lung epithelial cells.
• In vivo studies in mice evaluated mucosal IgA responses in the respiratory tract following CoMiP immunization.

Main Results:

• CoMiP effectively bind to and are internalized by alveolar macrophages.
• CoMiP demonstrated pleiotropic transfection of macrophages and lung epithelial cells in vitro.
• In vivo immunization with CoMiP resulted in elevated mucosal IgA levels in the respiratory tract.

Conclusions:

• Inhalable CoMiP represent a promising needle-free vaccine strategy for COVID-19.
• CoMiP's design effectively targets lung macrophages, eliciting a localized mucosal immune response.
• This approach could overcome barriers associated with traditional injectable vaccines, improving accessibility and compliance.