Journal Article

RBD-displaying OMV nanovaccine boosts immunity against SARS-CoV-2

Cheng, Hao, Feng, Rang, Jin, Zhe, Liu, Jing-Yi, Li, Hai-Bo, Xue, Ruo-Yi, Deng, Yan, Zhang, Shan-Shan, Zou, Quan-Ming, Li, Guo-Cheng, Liu, Chang, Guo, Man-Ying

2025

Overview

Background Since the emergence of SARS-CoV-2, the causative agent of COVID-19, the global health landscape has confronted an unprecedented and formidable challenge. The SARS-CoV-2 receptor-binding domain (RBD) is a key antigen in vaccine design. However, its low immunogenicity has been a hurdle, resulting in the production of minimal anti-RBD antibodies even when combined with alum adjuvant. Outer membrane vesicles (OMVs), secreted by Gram-negative bacteria, are nanospherical structures that can display or deliver antigens while also providing adjuvant activity through pathogen-associated molecular patterns (PAMPs). Results In this study, we utilized the SpyTag (ST)/SpyCatcher (SC) bioconjugation system to couple OMV and SARS-CoV-2 RBD in vitro. We successfully prepared a ‘plug-and-display’ nanovaccine OMV-RBD, which demonstrated good safety profiles and promoted the uptake of antigens by DCs and the maturation of BMDCs by activating TLR3 and NOD2 signaling pathways. Both intranasal and intramuscular immunization with OMV-RBD vaccine elicited robust antigen-specific humoral and cellular immune responses. Importantly, the induced antibodies effectively inhibited the binding of RBD to human angiotensin-converting enzyme 2 (hACE2) and neutralized SARS-CoV-2 pseudoviruses. Conclusions This vaccine platform offers an alternative strategy for developing recombinant subunit vaccines against SARS-CoV-2, potentially enhancing immune responses and improving vaccine efficacy. Graphical abstract

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: ACE2 / Adenoviruses / Adjuvants / Angiotensin / Angiotensin-Converting Enzyme 2 / Animals / Antibodies / Antibodies, Neutralizing - immunology / Antibodies, Viral - immunology / Antigens / Bacteria / Binding / Biotechnology / Cell organelles / Chemistry / Chemistry and Materials Science / COVID-19 / COVID-19 - immunology / COVID-19 - prevention & control / COVID-19 Vaccines - administration & dosage / COVID-19 Vaccines - immunology / Disease transmission / E coli / Female / Genetic engineering / Global health / Gram-negative bacteria / Humans / Immune response / Immune response (cell-mediated) / Immune response (humoral) / Immunity, Cellular / Immunity, Humoral / Immunization / Immunogenicity / Mice / Mice, Inbred BALB C / Microscopy / Molecular Medicine / mRNA vaccines / Nanomedicine / Nanotechnology / Nanovaccines / NOD2 protein / Peptides / Peptidyl-dipeptidase A / Pharmaceutical research / Physiological aspects / Plasmids / Protein Domains / Proteins / Public health / Salmonella / SARS-CoV-2 - immunology / Severe acute respiratory syndrome coronavirus 2 / Spike Glycoprotein, Coronavirus - chemistry / Spike Glycoprotein, Coronavirus - immunology / TLR3 protein / Toll-like receptors / Vaccine efficacy / Vaccines / Viral antigens