Abstract The long-term effects of host factors on vaccine-elicited immune responses have not been well studied, and the interactions of host factors with annual influenza vaccinations are yet to be explored. We analyzed data from a cohort of 386 individuals who received the standard-dose influenza vaccine and enrolled in ≥2 seasons from 2016 to 2020. Our analyses indicated disparate vaccine-elicited immune responses between males and females in adults when they were repeatedly vaccinated for at least 2 seasons. Notably, we found interactive effects between age and body mass index (BMI) on overall immune responses, and between sex at birth and BMI in adults. Sex effect on vaccine-elicited immune responses was discovered for adults repeatedly vaccinated for at least 2 seasons. Notably, we found interactive effects between age and body mass index (BMI) on overall immune responses, and between sex and BMI in the adult age group.