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Br J Pharmacol . PLGA-particle-based vaccine induces SARS-CoV-2-specific antibody and T-cell responses

tetano

Editor, Senior Moderator
Br J Pharmacol


. 2026 Apr 1.
doi: 10.1111/bph.70423. Online ahead of print.
PLGA-particle-based vaccine induces SARS-CoV-2-specific antibody and T-cell responses

Dennis Horvath[SUP] 1 2 [/SUP], Katharina Inholz[SUP] 1 [/SUP], Dennis Mink[SUP] 1 2 3 [/SUP], Alicia Madel[SUP] 1 [/SUP], Julia Koerner[SUP] 1 [/SUP], Reinhold Horlacher[SUP] 4 [/SUP], Michael Basler[SUP] 1 3 [/SUP]


Affiliations
Abstract

Background and purpose: Current coronavirus disease 2019 (COVID-19) vaccines effectively prevent severe disease but induce primarily systemic immunity without mucosal protection in the respiratory tract, which is mandatory for protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the prevention of viral transmission. Vaccination strategies capable of inducing local immunity at the site of infection are therefore needed. Here, we evaluated a poly (lactic-co-glycolic acid) (PLGA) microparticle-based vaccine co-encapsulating the receptor binding domain (RBD) of SARS-CoV-2 Spike protein with the TLR3/RIG-1 agonist Riboxxim, employing a subcutaneous prime and intranasal boost immunization schedule.
Experimental approach: BALB/c mice received subcutaneous prime immunization followed by intranasal boost with PLGA microparticles containing RBD/Riboxxim. Antibody responses were assessed by enzyme-linked immunosorbent assay (ELISA), neutralization by competitive ELISA and T-cell responses by enzyme-linked immune spot assay, intracellular cytokine staining and flow cytometry. Memory responses were evaluated 30 days post boost immunization.
Key results: Vaccination induced robust RBD-specific IgG and IgA antibody titres in both serum and bronchoalveolar lavage fluid, with neutralizing capacity against the Wuhan-Hu-1 strain. Strong CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T-cell responses were detected systemically and in the respiratory tract. Importantly, the vaccine generated durable immunological memory, including tissue-resident memory T-cells in the respiratory tract and long-lived IgG and IgA memory B-cells in secondary lymphoid organs.
Conclusions and implications: PLGA microparticle-based vaccination induces potent systemic and mucosal immune responses against SARS-CoV-2 RBD. This adaptable platform represents a promising approach for mucosal vaccination strategies, with potential for rapid adaptation to emerging variants.

Keywords: PLGA; RBD; SARS‐CoV‐2; microparticle; microspheres; mucosal immunity; vaccine.

 
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