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A "Plug-And-Display" Nanoparticle Vaccine Platform Based on Outer Membrane Vesicles Displaying SARS-CoV-2 Receptor-Binding Domain
Published on: July 25, 2022
A Novel Bacterium-Like Particle Vaccine Displaying the MERS-CoV Receptor-Binding Domain Induces Specific Mucosal and
Entao Li1,2, Hang Chi3,4, Pei Huang2,5
1College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
Abstract:
Middle East respiratory syndrome coronavirus (MERS-CoV), a new coronavirus that has been causing severe and fatal acute respiratory illnesses in humans since its outbreak in 2012, has raised public fear worldwide. The development of prophylactics and therapeutics is urgently needed to prevent and control MERS-CoV infections. In this study, a bacterium (Lactococcus lactis)-like particle (BLP) vaccine displaying the MERS-CoV receptor-binding domain (RBD) was developed, and gram-positive enhancer matrix (GEM) particles were used as substrates to externally bind to the MERS-CoV RBD through a protein anchor (PA). The designs included different numbers of lysin motif (LysM) repeats in the PAs linked by linkers (RBD-linker-PA2 (RLP2), RBD-linker-PA3 (RLP3) and RBD-PA3 (RP3)), and three LysM repeats and a linker in the fusion proteins increased the binding activity to the RBD. The specific immune responses were tested by intranasally immunizing mice with RLP3-GEM with or without the adjuvant GEL01. The results showed that GEL01-adjuvanted RLP3-GEM increased the systemic humoral, cellular and local mucosal immune responses in the mouse model, especially in the intestinal tract. The above results indicate that the MERS-CoV BLP product has the potential to be developed into a promising mucosal candidate vaccine to protect against MERS-CoV infections.
Insights
A novel bacterium-like particle vaccine displaying the MERS-CoV receptor-binding domain shows promise for preventing Middle East respiratory syndrome coronavirus infections. Adjuvant-enhanced formulations stimulated robust immune responses in mice, particularly in mucosal tissues.
Area of Science:
- * Virology and Immunology
- * Vaccine Development
- * Infectious Disease Research
Background:
- * Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness and global concern since 2012.
- * Urgent need for effective prophylactics and therapeutics against MERS-CoV.
- * Bacterium-like particle (BLP) technology offers a novel vaccine platform.
Purpose of the Study:
- * To develop and evaluate a MERS-CoV receptor-binding domain (RBD)-displaying BLP vaccine.
- * To investigate the impact of protein anchor design on RBD binding and immunogenicity.
- * To assess the efficacy of the vaccine candidate in a mouse model.
Main Methods:
- * Engineered gram-positive enhancer matrix (GEM) particles to display MERS-CoV RBD via protein anchors (PA) with varying lysin motif (LysM) repeats.
- * Constructed fusion proteins: RBD-linker-PA2 (RLP2), RBD-linker-PA3 (RLP3), and RBD-PA3 (RP3).
- * Intranasal immunization of mice with RLP3-GEM, with or without GEL01 adjuvant, followed by immune response analysis.
Main Results:
- * Fusion proteins with three LysM repeats and a linker demonstrated enhanced RBD binding.
- * GEL01-adjuvanted RLP3-GEM significantly boosted systemic humoral and cellular immunity in mice.
- * The vaccine candidate induced strong local mucosal immune responses, notably in the intestinal tract.
Conclusions:
- * The MERS-CoV BLP vaccine candidate, particularly RLP3-GEM with adjuvant, effectively elicits comprehensive immune responses.
- * This BLP-based vaccine shows significant potential as a mucosal vaccine for MERS-CoV prevention.
- * Further development is warranted to establish this platform as a viable MERS-CoV prophylactic.
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