Intranasal Administration of RBD Nanoparticles Confers Induction of Mucosal and Systemic Immunity against SARS-CoV-2.

Tuksin Jearanaiwitayakul,Panya Sunintaboon,Supaporn Phumiamorn,Suttikarn Apichirapokey,Mathurin Seesen,Sukathida Ubol,Runglawan Chawengkirttikul,Jitra Limthongkul,Sompong Sapsutthipas

doi:10.3390/vaccines9070768

Tuksin Jearanaiwitayakul, Panya Sunintaboon + Show 7 more

Open Access

https://doi.org/10.3390/vaccines9070768

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Abstract

Mucosal immunity plays a significant role in host defense against viruses in the respiratory tract. Because the upper respiratory airway is a primary site of SARS-CoV-2 entry, immunization at the mucosa via the intranasal route could potentially lead to induction of local sterilizing immunity that protects against SARS-CoV-2 infection. In this study, we evaluated the immunogenicity of a receptor-binding domain (RBD) of SARS-CoV-2 spike glycoprotein loaded into N,N,N-trimethyl chitosan nanoparticles (RBD-TMC NPs). We showed that intranasal delivery of RBD-TMC NPs into mice induced robust local mucosal immunity, as evidenced by the presence of IgG and IgA responses in BALs and the lungs of immunized mice. Furthermore, mice intranasally administered with this platform of immunogens developed robust systemic antibody responses including serum IgG, IgG1, IgG2a, IgA and neutralizing antibodies. In addition, these immunized mice had significantly higher levels of activated splenic CD4+ and CD8+ cells compared with those that were administered with soluble RBD immunogen. Collectively, these findings shed light on an alternative route of vaccination that mimics the natural route of SARS-CoV-2 infection. This route of administration stimulated not only local mucosal responses but also the systemic compartment of the immune system.

Highlights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recent emerging virus that has spread globally and poses a serious threat to society, leading to the instability of healthcare systems worldwide
We found that receptor-binding domain (RBD) protein was efficiently entrapped into TMC NPs
The results showed that encapsidated protein could be reacted with the tested antibodies (Figure 1B). These findings suggested that the ionotropic gelation method can be used to encapsulate the RBD antigen without interfering with RBD antigenicity

Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recent emerging virus that has spread globally and poses a serious threat to society, leading to the instability of healthcare systems worldwide. As of 5 June 2021, at least 171 million confirmed cases and 3.7 million deaths have been announced by the World Health Organization (WHO) (https://covid19.who.int/) (accessed on 5 June 2021). The severe disease is known as acute respiratory distress syndrome (ARDS), which is a disease associated with pneumonia, manifesting the signs of shortness of breath and hypoxia [2]. Individuals with immune impairment or underlying health problems, or aged over 60 years are at greater risk for progression to respiratory failure [3]. As the virus continues to spread rapidly across the world, build-up of herd immunity through mass immunization represents the most promising approach to confining this pandemic

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