PLGA-particle-based vaccine induces SARS-CoV-2-specific antibody and T-cell responses

Area of Science:

• Immunology
• Vaccinology
• Nanotechnology

Background:

• Current COVID-19 vaccines primarily induce systemic immunity, lacking mucosal protection in the respiratory tract.
• Respiratory mucosal immunity is crucial for preventing SARS-CoV-2 infection and transmission.
• There is a need for vaccination strategies that induce local immunity at the site of viral entry.

Purpose of the Study:

• To evaluate a poly (lactic-co-glycolic acid) (PLGA) microparticle-based vaccine for inducing systemic and mucosal immunity against SARS-CoV-2.
• To assess the immunogenicity of a vaccine co-encapsulating the SARS-CoV-2 receptor binding domain (RBD) and a TLR3/RIG-1 agonist (Riboxxim).
• To investigate the effectiveness of a subcutaneous prime and intranasal boost immunization schedule.

Main Methods:

• BALB/c mice were immunized via subcutaneous prime and intranasal boost with PLGA microparticles containing RBD/Riboxxim.
• Antibody responses were measured using ELISA and competitive ELISA for neutralization.
• T-cell responses were analyzed via ELISPOT assay, intracellular cytokine staining, and flow cytometry.

Main Results:

• The vaccine elicited robust RBD-specific IgG and IgA antibody titers in serum and bronchoalveolar lavage fluid.
• Neutralizing antibody activity against the Wuhan-Hu-1 strain was observed.
• Significant CD4+ and CD8+ T-cell responses were detected systemically and within the respiratory tract.
• Durable immunological memory, including tissue-resident memory T-cells and long-lived memory B-cells, was established.

Conclusions:

• PLGA microparticle-based vaccination effectively induces potent systemic and mucosal immune responses against SARS-CoV-2 RBD.
• This vaccination platform shows promise for developing effective mucosal vaccines against respiratory viruses.
• The adaptable nature of this platform allows for potential rapid modification to target emerging SARS-CoV-2 variants.