High affinity antibodies (Abs) for target antigens (Ags) on pathogens are critical components of vaccines. Long-lived plasma cells and memory B cells, effector B cells that are responsible for production of high affinity Abs, develop predominantly from germinal centers. Follicular helper T (Tfh) cells provide help B cells to form germinal centers. Therefore, for development of efficacious vaccines, it is critical to understand how to regulate Tfh cell differentiation and functions and which Ags to choose among proteins that are present on pathogens as a target for high affinity Abs. We produced virus-like particles (VLPs) that express hemagglutinin (HA) of influenza A virus (IAV) A/PR/8/1934 (H1N1) and OTII peptide (OVA323-339) to analyze B and T cell responses in Ag-specific manners. To elicit Ab responses to the stalk region of A/PR/8/1934, where genetic information has been relatively conserved among heterologous H1N1 IAV, VLPs were engineered to express HA (headless HA, HD’less HA), whose globular head region was removed. Upon immunization of VLPs adjuvanted with Addavax, Abs were strongly induced against A/PR/8/1934 HA with concomitant induction of Tfh differentiation of OTII cells. Moreover, in contrast to NR4542, a mouse monoclonal Ab developed against globular head region of A/PR/8/1934, which exhibits mono-specificity for A/PR/8/1934 HA, Abs produced by VLP immunization were capable to bind to HA of heterologous H1N1 IAV, in addition to one of A/PR/8/1934. Collectively, our data suggest VLP immunization system could serve for a valuable system to develop efficacious vaccines.