Intranasal Multiepitope PD-L1-siRNA-Based Nanovaccine: The Next-Gen COVID-19 Immunotherapy

Area of Science:

• Nanotechnology
• Immunology
• Virology

Background:

• Current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, while effective at reducing disease severity, have limitations in preventing infection.
• There is a global need for novel vaccine technologies that can induce broader protection, particularly against respiratory viruses.

Purpose of the Study:

• To develop a flexible nanovaccine platform for nasal administration to induce mucosal immunity against SARS-CoV-2.
• To create a next-generation multiepitope nanovaccine co-delivering immunogenic peptides, adjuvants, and PD-L1 regulators.

Main Methods:

• Utilized an immunoinformatic workflow to select immunogenic SARS-CoV-2 peptides.
• Developed a nanovaccine platform for co-delivery of peptides, adjuvants, and PD-L1 regulators.
• Assessed the nanovaccine's ability to induce local and systemic immune responses, including immunoglobulin A (IgA) secretion.

Main Results:

• The nanovaccine platform successfully evoked both local and systemic cellular and humoral immune responses against SARS-CoV-2.
• Induced secretion of neutralizing immunoglobulin A (IgA) against SARS-CoV-2, including variants of concern.
• Demonstrated long-term stability of the lyophilized nanovaccine at room temperature, retaining in vivo efficacy after reconstitution.

Conclusions:

• The developed nanovaccine platform provides a promising strategy for inducing effective mucosal immunity against SARS-CoV-2 and other respiratory viruses.
• The room-temperature stability of the lyophilized formulation is particularly advantageous for global distribution, especially in developing countries.
• This modular nanovaccine system offers adaptability for addressing future viral threats.