Collectively, our data demonstrates that intranasal delivery of a neutralizing nanobody IgA-Fc fusion protects animals from infection of SARS-CoV-2 VOC, and the results strongly suggest that the IgA-Fc fused nanobody provides a greater level of protection in the mucosal lining of the nasal passages and lungs, as either an immunoprophylaxis or post-exposure treatment, than the monomeric nanobody. This evidence concerns the gene CD79A and infection.