Individuals with occupational exposure to swine may have disproportionate risk for zoonosis with swine influenza A virus (IAV). To evaluate human antibody responses, sera or plasma from swine veterinarians, swine farm employees, and the general population were tested by hemagglutination inhibition (HI) assays against representative swine and human seasonal influenza vaccine strains. HI data were analyzed by antigenic cartography to assess strain relationships, and reproduction number modeling to evaluate pandemic potential using age-stratified immunity profiles. Occupationally exposed groups had lower human seasonal vaccine uptake (45.5% vs 70%) and significantly lower odds of seropositivity to several H1 and H3 from swine compared to general population cohorts. One swine strain exhibited significant antigenic drift (3.62 AU) from its nearest vaccine strain. Multiple strains required lower R? thresholds for pandemic spread (1.09-1.35) than recorded pandemic strains (1.46-1.80). This demonstrates that population immunity gaps heighten zoonotic risk to circulating swine H1 and H3 strains.