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

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.

COVID-19 intranasal vaccines: current progress, advantages, prospects, and challenges

“…Not only did this mode of delivery activates local mucosal responses, but it also activated the immune system’s systemic component. 72 …”

Peritoneal Administration of a Subunit Vaccine Encapsulated in a Nanodelivery System Not Only Augments Systemic Responses against SARS-CoV-2 but Also Stimulates Responses in the Respiratory Tract

“…The purified protein was evaluated by immunoblotting analysis using mouse anti-His (C-term) antibodies (Invitrogen, Carlsbad, CA, USA) and rabbit anti-SARS-CoV-2 receptor-binding domain (RBD) polyclonal antibodies (Sino Biological, Beijing, China). The SARS-CoV-2 RBD protein used throughout the study was prepared in-house as previously described [22].…”

“…The optical density (OD) at 450 nm was read using an ELISA reader. The cut-off endpoint titers (EPT) of antigen-specific antibodies were shown as the reciprocal of the highest dilution of samples with an OD value equal to or more than three times the OD value of blank controls [22].…”

“…The virus-antibody mixture was further incubated at 37 • C for 1 h before being inoculated into a monolayer of Vero cells. The plaque assay was then performed as described previously [22]. The neutralizing titers (PRNT 50 ) that conferred plaque reduction at 50% were calculated compared with the virus control (virus alone).…”

A chitosan-mediated inhalable nanovaccine against SARS-CoV-2

“…Chitosan (CS), with positive charges, is a natural mucoadhesive material with cGAS-STING-dependent adjuvanticity [22][23][24]. Many studies have indicated that chitosan is an effective mucosal vaccine adjuvant for many antigens [25][26][27], such as ovalbumin protein (OVA) [25] and receptor-binding domain (RBD) of SARS-CoV-2 spike protein [27]. Additionally, chitosan can open intercellular tight junctions temporarily [28], which is beneficial for drugs to pass through the intercellular space, thus improving tissue penetration and amplifying humoral and cellular immunity.…”