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Engineered Nanovesicles Expressing Bispecific Single Chain Variable Fragments to Protect against SARS-CoV-2 Infection
Lantian Tang1, Hanxi Ding1, Qi Zeng2
1Center for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China.
ACS Biomaterials Science & Engineering
|November 16, 2023
Summary
Novel nanovesicles targeting the SARS-CoV-2 spike protein and dendritic cells offer potential long-term protection against reinfection and disease progression by boosting immune response.
Area of Science:
- Immunology
- Nanotechnology
- Virology
Background:
- Coronavirus disease 2019 (COVID-19) poses ongoing risks due to persistent reinfection potential from waning immunity.
- Existing treatments face challenges in providing long-term immune protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection.
Purpose of the Study:
- To develop novel bispecific nanovesicles (NVs) for dual targeting of SARS-CoV-2 and immune cells to enhance long-term protection.
- To investigate the potential of nanovesicles engineered to express CB6 and dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) single chain variable fragments (scFvs) for virus neutralization and immune activation.
Main Methods:
- Engineered nanovesicles (NVs) displaying CB6 and DC-SIGN scFvs on their surface.
- Incorporation of monophosphoryl lipid A (MPLA) as an adjuvant within the NVs.
- In vitro assessment of NVs' ability to block pseudovirus infection and activate dendritic cells (DCs).
- In vivo evaluation in a mouse model to determine effects on neutralizing antibody titers and tumor growth.
Main Results:
- CB6/DC-SIGN NVs successfully prevented SARS-CoV-2 pseudovirus infection of target cells in vitro.
- NVs demonstrated significant activation of DCs, enhanced by the MPLA adjuvant.
- Mouse models showed improved neutralizing antibody titers and inhibited tumor growth associated with SARS-CoV-2 spike protein expression after treatment.
Conclusions:
- The developed CB6/DC-SIGN NVs show promise for both short-term blocking of SARS-CoV-2 and long-term immune memory against secondary infections.
- This nanovesicle-based strategy offers a potential new therapeutic approach for managing COVID-19 and related complications.
