The levels of anti-SARS-CoV-2 antibody were detected using HRP-labeled goat anti-mouse IgG (1:3000, Invitrogen) or IgA antibody (1:4000, Southern Biotech, Birmingham, AL, USA), respectively

The levels of anti-SARS-CoV-2 antibody were detected using HRP-labeled goat anti-mouse IgG (1:3000, Invitrogen) or IgA antibody (1:4000, Southern Biotech, Birmingham, AL, USA), respectively. CYFIP1 to neutralize both the wild-type and Delta variant strains of SARS-CoV-2. Significantly, the intranasal immunization also stimulated systemic responses. This is evidenced by the increased production of circulating IgG and IgA, which were able to neutralize and bind specifically to the SARS-CoV-2 virion and spike protein. Additionally, this intranasal administration potently activated a splenic T cell response and the production of Th-1 cytokines, suggesting that this vaccine may well activate a cellular response in the respiratory tract. The results demonstrate that STING agonist strongly acts as an adjuvant to the immunogenicity of S-NPs. This platform may be an ideal vaccine against SARS-CoV-2. Keywords:intranasal COVID-19 vaccine, SARS-CoV-2 spike glycoprotein, adjuvant nanodelivery, STING agonist, immunogenicity == 1. Introduction == In December of 2019, a member of the RNA beta coronaviruses emerged. It is known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]. SARS-CoV-2 is the causative agent of the clinical disease called COVID-19. SARS-CoV-2 rapidly spread into 220 countries. This has resulted in at least 507 million confirmed cases and more than 6.2 million deaths, as announced by the World Health Organization (WHO) on 25 April 2022 (https://covid19.who.int/(accessed on 25 April 2022)). COVID-19 is the third respiratory pandemic caused by infection with a novel coronavirus, with the first and the second ones being SARS (severe acute respiratory syndrome) and MERS (middle east respiratory syndrome), respectively. The severe form of the COVID-19 disease is associated primarily Haloperidol D4 with fever, cough, shortness of breath, and serious lung syndromes, including acute respiratory distress syndrome (ARDS) and cytokine release syndrome (CRS) [2]. The uniqueness of the SARS-CoV-2 infection compared with SARS and MERS is that viral particles are shed during the presymptomatic phase of infection. This has led to the significant spread of the virus worldwide [3]. One approach to stop this pandemic is global immunization with an effective anti-COVID-19 vaccine. The ideal vaccine against SARS-CoV-2 is a vaccine that acts against infection, disease progression, or transmission [4]. Three platforms of anti-COVID-19 vaccines have recently been launched for human immunization. These are the viral vector vaccines, Haloperidol D4 the nucleic-acid-based vaccines (mRNA vaccine and DNA vaccine), and the non-replicating vaccines (the killed-virus vaccine and the virus-like particle and protein subunit vaccine) Haloperidol D4 [5,6]. The vaccines for emergency use are administered via an intramuscular injection. These vaccines stimulate potent systemic responses against SARS-CoV-2, while specific responses in the primary target organ remain doubtful, as supported by a breakthrough infection by certain genotypes of SARS-CoV-2 in certain vaccinated populations [7]. This may, of course, be due to the continuous evolution of the virus [8] and the sub-neutralizing levels of anti-SARS-CoV-2 responses in the main target organ, the respiratory tract. The transmission of SARS-CoV-2 mainly occurs via exposure to respiratory secretions and contaminated surfaces, as well as the inhalation of virus particles in the air [9,10]. However, there is also a report of viral shedding through the fecal route [11]. This is evidenced by the presence of the SARS-CoV-2 genome in fecal specimens from COVID-19 patients [12]. Interestingly, spontaneous replication of SARS-CoV-2 was observed in the bacterial cultures of patients feces for up to 30 days and beyond [13]. This suggests the association between SARS-CoV-2 and gut microbiota. This may contribute, more or less, to pathogenesis and the mode of transmission. This virus utilizes angiotensin-converting enzyme 2 (ACE2), which is highly expressed in the nasal epithelium, for its entry [14,15]. The major target organ of SARS-CoV-2 is the respiratory tract; thus, complications of COVID-19 are commonly pulmonary. Therefore, an effective vaccine should stimulate strong protective immunity in the respiratory tract. In other words, a vaccine that is delivered via the intranasal route may be a challenging alternative. Nasal-associated lymphoid tissue (NALT) anatomically located in the nasopharynx and oropharynx area is an immune inductive site and a primary target for intranasal vaccines [16]. An example of an advanced intranasal vaccine for human use is influenza vaccines, including the FluMisttrivalent and quadrivalent seasonal flu vaccines and Nasovac-S [17,18,19]. Both of them are intranasal multivalent vaccines. The FluMisttrivalent vaccine has been approved by US FDA, and is designed to act against two influenza A and one influenza B strains and be able to stimulate strong immunity in individuals aged 249 years [17,18]. Nasovac-S is currently licensed in.