Current Australian vaccination policy recommends annual influenza vaccination for people aged ≥6 months to reduce the likelihood of becoming ill with influenza. This is because influenza vaccines are updated frequently, when circulating strains acquire immune escape mutations. However, despite careful selection of vaccine strains, there is great variation in vaccine responses between individuals and in vaccine effectiveness between seasons. It is not clear whether antibodies and memory B cells induced by prior influenza exposures affect the response to new vaccine strains. Previous studies documenting lower vaccine effectiveness with increasing years of annual vaccination suggest a negative effect on recruitment of naïve B-cells reactive with new strain epitopes. To better understand the effect of prior influenza exposure, we investigated influenza vaccine responses in influenza vaccine-naïve participants in Vietnam who had undergone active influenza surveillance since 2007, and were vaccinated, for the first time, with inactivated trivalent influenza vaccine in 2016. Twenty-eight participants had no A/H3N2 infection and seventy-two had at least one infection during the surveillance period. Blood was collected at baseline (on day (d) 7 prior to vaccination), and at d4, d7, d14, d21 and d280 after vaccination. We aimed to determine the relationship between hemagglutination-inhibition (HI) titers to vaccine- and past-A/H3N2 strains and the recruitment of memory versus naïve B-cells to the response. Post-vaccine antibody titers were high relative to studies in settings where influenza vaccination is common. Interestingly, individuals who had been infected with A/H3N2 viruses had greater responses than those who had not been infected, which contrasts with other studies showing an incremental negative effect of prior vaccination on titers. Further analysis of the responding B cells, and comparison with groups that are annually vaccinated may provide insights into how to generate an optimal immune response to influenza vaccination and avoid any negative effects of repeated vaccination.