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The emerging SARS-CoV-2 variants of concern (VOCs) threaten the effectiveness of current COVID-19 vaccines administered intramuscularly and designed to only target the spike protein. There is a pressing need to develop next-generation vaccine strategies for broader and long-lasting protection. Using adenoviral vectors (Ad) of human and chimpanzee origin, we evaluated Ad-vectored trivalent COVID-19 vaccines expressing spike-1, nucleocapsid, and RdRp antigens in murine models. We show that single-dose intranasal immunization, particularly with chimpanzee Ad-vectored vaccine, is superior to intramuscular immunization in induction of the tripartite protective immunity consisting of local and systemic antibody responses, mucosal tissue-resident memory T cells and mucosal trained innate immunity. We further show that intranasal immunization provides protection against both the ancestral SARS-CoV-2 and two VOC, B.1.1.7 and B.1.351. Our findings indicate that respiratory mucosal delivery of Ad-vectored multivalent vaccine represents an effective next-generation COVID-19 vaccine strategy to induce all-around mucosal immunity against current and future VOC. [Display omitted] • Two trivalent adenoviral-vectored COVID-19 vaccines were developed and evaluated • Intranasal, but not intramuscular, immunization induces tripartite mucosal immunity • Intranasal immunization protects against ancestral and variant strains of SARS-CoV-2 • Optimal protection requires B and T cell immunity and trained innate immunity Respiratory mucosal immunization with a next-generation adenoviral-vectored trivalent COVID-19 vaccine expressing spike, nucleocapsid, and RdRp antigens, induces all-around protective mucosal immunity against SARS-CoV-2 via induction of systemic and local antibodies, lung-tissue-resident memory T cells, and trained alveolar macrophages. [ABSTRACT FROM AUTHOR]