Responses of primary human nasal epithelial cellsto COVID-19 vaccine candidate
Phissinee Jakaew,1 Tuksin Jearanaiwitayakul,2 Panuwat Midoeng,3 Promsin Masrinoul,4 Panya Sunintaboon,5 Sukathida Ubol1
Affiliations:
1 Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand
2 Department of Clinical Pathology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand
3 Division of Pathology, Army Institute of Pathology, Phramongkutklao Hospital, Bangkok, Thailand
4 Center for Vaccine Development, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand
5 Department of Chemistry, Faculty of Science, Mahidol University, Salaya, Nakhon Pathom, Thailand
Abstract
Background: Upper respiratory tract is the primary target of SARS-CoV-2. Therefore, nasal immune responses act as the first line of defense against SARS-CoV-2 infection.
Objective: We aim to investigate the immune responses of human nasal epithelial cells (HNEpCs) upon stimulation with a COVID-19 vaccine candidate. This candidate named RBD-NPs is composed of SARS-CoV-2 receptor-binding domain (RBD) encapsulated within the N,N,N-trimethyl chitosan nanoparticles (TMC-NPs).
Methods: HNEpCs were stimulated with RBD-NPs, empty NPs, or soluble RBD at various concentrations. After 24 and 48 h of treatment, cells viability and delivery of the immunogens were assessed using XTT assay and flow cytometry. Levels of cytokines and chemokines in the supernatant were quantified with Bio-plex Human Cytokine Assay. Communication between RBD-NPs-stimulated HNEpCs and monocyte-derived dendritic cells (MoDCs) was assessed through differentiation of MoDCs into mature phenotype.
Results: RBD-NPs as high as 100 µg exerted no toxicity to HNEpCs and could effectively be delivered to HNEpCs. Treatment of HNEpCs with RBD-NPs strongly activated production of several pro-inflammatory cytokines, chemokines, Th1-related cytokines and the monocytes/macrophages growth factors. Interestingly, soluble mediators secreted from RBD-NPs treated HNEpCs significantly upregulated the expression of maturation markers (CD80, CD83, CD86 and HLA-DR) on the MoDCs.
Conclusion: This study demonstrated that our COVID-19 vaccine candidate drove HNEpCs into immunologically competent cells that not only exerted anti-viral innate immune responses but also potently induced MoDCs maturation.
Key words: SARS-CoV-2, COVID-19 vaccine, primary human nasal epithelial cells, RBD, delivery systems