In this groundbreaking study, researchers developed a mucosal adenoviral-vector vaccine, ChAd-SARS-CoV-2-S, which demonstrated sustained and robust immunity against a challenging Omicron variant in nonhuman primates, indicating a promising direction for durable COVID-19 protection strategies. Unlike traditional intramuscular vaccines, this mucosal vaccine elicited a comprehensive immune response, potentially paving the way for more effective and long-lasting COVID-19 vaccines.