We conducted a randomized, controlled phase I trial (NCT05397119) of a novel adjuvanted recombinant influenza A/H5 (A/Indonesia/05/2005, clade 2.1) hemagglutinin vaccine, administered intranasally in two doses 28 days apart at three antigen levels. Control groups received unadjuvanted recombinant H5 or formulation buffer placebo. Six months later, participants received a heterologous unadjuvanted inactivated influenza A/H5N1 (A/Vietnam/1203/2004, clade 1) vaccine intramuscularly. All vaccines were safe and well tolerated. After the primary intranasal series, serum hemagglutination inhibition and microneutralization responses were minimal. Increases in mucosal and serum IgG/IgA, serum surface plasmon resonance antibody binding, memory B cell and CD4 T cell activity, and antibody-dependent cell-mediated cytotoxicity were observed only in recipients primed intranasally with adjuvanted H5 vaccine. Following the inactivated H5N1 boost, robust responses across all immune assays, as well as microneutralization responses against diverse H5N1 clades (including currently circulating clade 2.3.4.4b), occurred in adjuvanted vaccine recipients, demonstrating successful priming and broad responses.