Kinetics of IgA Subtypes and Cytokines in Respiratory Secretions Following Immunization With COVID-19 Mucosal Vaccine

The COVID-19 pandemic highlights the need for mucosal vaccines inducing respiratory secretory IgA (sIgA), as traditional intramuscular vaccines primarily elicit systemic IgG with limited mucosal protection. This study systematically compared mucosal immune responses induced by two authorized COVID-19 mucosal vaccines: an orally aerosolized adenovirus vector-based vaccine (Ad5-nCoV) and an intranasal live-attenuated influenza virus vector-based vaccine (dNS1-RBD). We longitudinally assessed IgA, IgA1, and IgA2 antibody titers against SARS-CoV-2 RBD/Spike protein, alongside cytokine profiles, in nasal secretions and sputum from 40 participants at 7, 14, 28 days, and 3/6 months post-immunization. The orally aerosolized vaccine exhibited superior mucosal immunogenicity, with peak IgA positive conversion rate of 50% (nasal) and 65% (sputum) vs. 30% (nasal) and 40% (sputum) for the intranasal vaccine. Notably, the orally aerosolized vaccine induced sustained IgA2 dominance (> 50%) in sputum at 6 months, whereas the intranasal vaccine showed transient IgA1 predominance followed by decline. Despite these differences, both vaccines elicited modest overall mucosal responses, with only IL-6 showing significant intergroup variation (p < 0.01). This is a study to demonstrate compartmentalized IgA subclass dynamics between upper (nasal) and lower (sputum) respiratory tracts following mucosal vaccination. Our findings highlight the need for optimized mucosal vaccine formulations to enhance respiratory immunity, providing critical insights for developing next-generation COVID-19 vaccines targeting the complex mucosal immune microenvironment.