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

Abstract

The COVID-19 pandemic has currently created an unprecedented threat to human society and global health. A rapid mass vaccination to create herd immunity against SARS-CoV-2 is a crucial measure to ease the spread of this disease. Here, we investigated the immunogenicity of a SARS-CoV-2 subunit vaccine candidate, a SARS-CoV-2 spike glycoprotein encapsulated in N,N,N-trimethyl chitosan particles or S-TMC NPs. Upon intraperitoneal immunization, S-TMC NP-immunized mice elicited a stronger systemic antibody response, with neutralizing capacity against SARS-CoV-2, than mice receiving the soluble form of S-glycoprotein. S-TMC NPs were able to stimulate the circulating IgG and IgA as found in SARS-CoV-2-infected patients. In addition, spike-specific T cell responses were drastically activated in S-TMC NP-immunized mice. Surprisingly, administration of S-TMC NPs via the intraperitoneal route also stimulated SARS-CoV-2-specific immune responses in the respiratory tract, which were demonstrated by the presence of high levels of SARS-CoV-2-specific IgG and IgA in the lung homogenates and bronchoalveolar lavages of the immunized mice. We found that peritoneal immunization with spike nanospheres stimulates both systemic and respiratory mucosal immunity.

Mice immunized with trimethyl chitosan nanoparticles containing DENV-2 envelope domain III elicit neutralizing antibodies with undetectable antibody-dependent enhancement activity

“…This agrees with other works. For example, TMC NPs could efficiently enhance the uptake of various immunogens, such as DENV-2 NS1 [32], UV-DENV-2 [33], HA2 and NP proteins of influenza virus [40], SARS-CoV-2 RBD [34], and SAR-CoV-2 spike protein [35] to target cells. Moreover, TMC also provides an adjuvant effect, which is evidenced through the activation of an immune response against pathogens [31][32][33].…”

“…More importantly, activated DCs produce both Th1-and Th2-driven cytokines, suggesting that these nanoparticles may activate a DENV-specific T cell response, as well as an antibody response [31]. TMC NP-based vaccines have previously been developed against many viral pathogens, including DENV-2 [32,33], SARS-CoV-2 [34,35], and influenza [36]. Interestingly, these vaccines are highly immunogenic and activate a robust immune response against the viruses.…”

A clinical perspective of chitosan nanoparticles for infectious disease management

“…In this finding for a non-replicating dengue vaccine, an ultra-irradiation (UV)-inactivated DENV-2 carried by N , N , N -trimethyl chitosan nanoparticles (UV-inactivated DENV2 TMC NPs) emerged as a potential candidate. Analyzing TMC in a human ex vivo model, the human monocyte-derived dendritic cells (MoDCs) behaved to be both potential adjuvant and vaccine vehicles [ 80 ]. Moreover, dengue vaccines developed from UV-activated DENV-2 (UNI-DENV) and Mycobacterium bovis Bacillus Calmette–Guerin cell wall components (BCG-CWCs) were served by CS-NPs as a delivery system and potential adjuvant [ 41 ].…”

T cells in SARS-CoV-2 infection and vaccination

“… 136 Peritoneal delivery of spike encapsulated in N,N,N -trimethyl chitosan particles to mice induced strong T-cell responses. 137 A synthetic peptide vaccine with Freund’s adjuvant consisting of spike 446-480 protected mice from a lethal dose of SARS-CoV-2. 138 Spike protein given along with CpG adjuvant, together encapsulated in an artificial cell membrane polymersome, which produces a self-assembling nanoscale vesicle, induced functional memory CD4 + and CD8 + T cells in mice.…”