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Polymerized porin as a novel delivery platform for coronavirus vaccine
Zhongqian Yang1, Liangqun Hua1,2, Mengli Yang3
1Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, 650031, China.
Insights
Researchers developed a novel nanopore vaccine platform using polymerized receptor-binding domain (RBD) proteins. This cost-effective approach for a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine elicits strong neutralizing antibody and cellular immune responses.
Area of Science:
- Biotechnology
- Immunology
- Vaccine Development
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a significant global health threat.
- Efficient and cost-effective vaccine production is crucial for pandemic response.
- The receptor-binding domain (RBD) is a key target for neutralizing antibodies.
Purpose of the Study:
- To develop a novel nanopore-based vaccine platform for SARS-CoV-2.
- To investigate the potential of polymerized RBD displayed on a nanopore structure.
- To assess the immunogenicity and efficacy of this novel vaccine candidate.
Main Methods:
- Construction of a ClyA-RBD nanopore using principles of ClyA porin polymerization.
- Extraction of the ClyA-RBD nanopore from bacterial outer membranes using surfactants.
- Application of the polymerized porin (RBD-PP) platform for subunit vaccine fabrication.
Main Results:
- The polymerized RBD on the ClyA-RBD nanopore (RBD-PP) displays correct conformational epitopes.
- RBD-PP nanostructures effectively target lymph nodes, enhancing antigen presentation by dendritic cells.
- The vaccine candidate elicited anti-SARS-CoV-2 neutralizing antibodies, systemic cellular immunity, and memory T cells.
Conclusions:
- The developed PP-based vaccine platform provides a foundation for inexpensive SARS-CoV-2 vaccines.
- This novel platform demonstrates potential for inducing robust humoral and cellular immunity.
- The platform may have broader applications in developing vaccines against other pathogens and for drug delivery.
Abstract:
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), seriously threatens human life and health. The correct folding and polymerization of the receptor-binding domain (RBD) protein of coronavirus in Escherichia coli may reduce the cost of SARS-CoV-2 vaccines. In this study, we constructed this nanopore by using the principle of ClyA porin polymerization triggered by the cell membrane. We used surfactants to "pick" the ClyA-RBD nanopore from the bacterial outer membrane. More importantly, the polymerized RBD displayed on the ClyA-RBD polymerized porin (RBD-PP) already displays some correct spatial conformational epitopes that can induce neutralizing antibodies. The nanostructures of RBD-PP can target lymph nodes and promote antigen uptake and processing by dendritic cells, thereby effectively eliciting the production of anti-SARS-CoV-2 neutralizing antibodies, systemic cellular immune responses, and memory T cells. We applied this PP-based vaccine platform to fabricate an RBD-based subunit vaccine against SARS-CoV-2, which will provide a foundation for the development of inexpensive coronavirus vaccines. The development of a novel vaccine delivery system is an important part of innovative drug research. This novel PP-based vaccine platform is likely to have additional applications, including other viral vaccines, bacterial vaccines, tumor vaccines, drug delivery, and disease diagnosis.
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