Discussion
toxicity
VIRUS, ADVERSE EVENTS, INFLAMMATION, CAVITY, CYTOTOXICITY
NAS is a medical device innovated to support mucosal immunity against SARS-CoV-2 via a dual mechanism of action in which a potent broadly neutralizing human IgG1 anti-SARS-CoV-2 monoclonal antibody cocktail produces inhibitory effects against multiple variants of concern (VOCs) in nasal fluid, and a steric barrier-forming agent, HPMC, fortifies the mucus layer. NAS exhibited broadly neutralizing activities against SARS-CoV-2 pseudoviruses of ancestral, Alpha, Delta, Omicron BA.1, BA.2, BA.4/5, and BA.2.75 variants. To evaluate the safety and efficacy of NAS, preclinical studies were conducted following the ISO 10993 standards of medical devices. These studies showed good biocompatibility based on cytotoxicity, skin sensitization, and intracutaneous reactivity evaluations as well as satisfactory safety profiles by both acute and subacute systemic toxicity investigations. In animal studies, intranasal administration of NAS did not result in any detection of human IgG1 anti-SARS-CoV-2 antibodies in the bloodstream of rats at any time point during the 120 h of follow-up. This finding agrees with the knowledge that the nasal epithelial barrier only allows the passage of molecules smaller than 1000 DaThe randomized, placebo-controlled trial was conducted to assess the tolerability and effects of intranasal administration of NAS in 36 healthy participants. The trial revealed that NAS was well tolerated, without any changes in nasal mucosa appearance, any signs of inflammation, or any treatment-emergent adverse events for the entire 14 days of the study. Recently, the neutralizing antibody level in nasal fluids has been shown to correlate with the potential protective effects against Omicron infectionThe formulation of the NAS appears to be a significant factor contributing to its efficacy. This nasal spray uses HPMC, a compound commonly employed in pharmaceutical applications, especially as a viscosity enhancer that helps extend the retention time of the antibodies in the nasal cavity by reducing mucociliary clearanceNasal sprays with antibodies hold potential for protecting individuals at risk of virus exposure according to the classic susceptible-exposed-infectious-removed (SEIR) mathematical modelWhile NAS shows promise in supporting mucosal immunity against SARS-CoV-2, it is important to acknowledge its limitations. Widespread and long-term administration of nasal sprays with antibodies poses logistical challenges. Additionally, relying solely on intranasal antibody prophylaxis cannot prevent the widespread transmission of the virus within a community. Therefore, NAS should be used in conjunction with other protective measures, such as non-pharmaceutical interventions, to fill the gap during the time needed to develop and manufacture effective vaccines. This approach can complement active immunization strategies and provide an additional layer of protection.Collectively, NAS has shown safety and efficacy in increasing neutralizing antibodies in nasal fluids. However, to fully demonstrate the effectiveness of NAS in preventing COVID-19, a large-scale efficacy trial measuring COVID-19 incidence would be necessary. Further research and evaluation are needed to determine the potential role of NAS as a complementary tool in the fight against SARS-CoV-2.